Nanoparticle-Based Strategies to Combat COVID-19
- Riddhiman Medhi
Riddhiman MedhiDepartment of Chemistry and the Texas Center for Superconductivity, University of Houston, 4800 Calhoun Road, Houston, Texas 77204-5003, United StatesMore by Riddhiman Medhi
- ,
- Pannaree Srinoi
Pannaree SrinoiDepartment of Chemistry and the Texas Center for Superconductivity, University of Houston, 4800 Calhoun Road, Houston, Texas 77204-5003, United StatesMore by Pannaree Srinoi
- ,
- Nhat Ngo
Nhat NgoDepartment of Chemistry and the Texas Center for Superconductivity, University of Houston, 4800 Calhoun Road, Houston, Texas 77204-5003, United StatesMore by Nhat Ngo
- ,
- Hung-Vu Tran
Hung-Vu TranDepartment of Chemistry and the Texas Center for Superconductivity, University of Houston, 4800 Calhoun Road, Houston, Texas 77204-5003, United StatesMore by Hung-Vu Tran
- , and
- T. Randall Lee*
T. Randall Lee*Email: [email protected]. (T.R.L.)Department of Chemistry and the Texas Center for Superconductivity, University of Houston, 4800 Calhoun Road, Houston, Texas 77204-5003, United StatesMore by T. Randall Lee
Copyright © 2020 American Chemical Society
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Abstract
Coronavirus disease 2019 (COVID-19) is the worst pandemic disease of the current millennium. This disease is caused by the highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first exhibited human-to-human transmission in December 2019 and has infected millions of people within months across 213 different countries. Its ability to be transmitted by asymptomatic carriers has put a massive strain on the currently available testing resources. Currently, there are no clinically proven therapeutic methods that clearly inhibit the effects of this virus, and COVID-19 vaccines are still in the development phase. Strategies need to be explored to expand testing capacities, to develop effective therapeutics, and to develop safe vaccines that provide lasting immunity. Nanoparticles (NPs) have been widely used in many medical applications, such as biosensing, drug delivery, imaging, and antimicrobial treatment. SARS-CoV-2 is an enveloped virus with particle-like characteristics and a diameter of 60–140 nm. Synthetic NPs can closely mimic the virus and interact strongly with its proteins due to their morphological similarities. Hence, NP-based strategies for tackling this virus have immense potential. NPs have been previously found to be effective tools against many viruses, especially against those from the Coronaviridae family. This Review outlines the role of NPs in diagnostics, therapeutics, and vaccination for the other two epidemic coronaviruses, the 2003 severe acute respiratory syndrome (SARS) virus and the 2012 Middle East respiratory syndrome (MERS) virus. We also highlight nanomaterial-based approaches to address other coronaviruses, such as human coronaviruses (HCoVs); feline coronavirus (FCoV); avian coronavirus infectious bronchitis virus (IBV); coronavirus models, such as porcine epidemic diarrhea virus (PEDV), porcine reproductive and respiratory syndrome virus (PRRSV), and transmissible gastroenteritis virus (TGEV); and other viruses that share similarities with SARS-CoV-2. This Review combines the salient principles from previous antiviral studies with recent research conducted on SARS-CoV-2 to outline NP-based strategies that can be used to combat COVID-19 and similar pandemics in the future.
Note
This article is made available via the ACS COVID-19 subset for unrestricted RESEARCH re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
1. Introduction
ARTICLE SECTIONS
A novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused an outbreak of the pulmonary disease called coronavirus disease 2019 (COVID-19), starting in December 2019 in the city of Wuhan in China. (1−3) The primary symptoms of COVID-19 include fever, severe respiratory illness, pneumonia, and dyspnea. (1,2) Since the initial outbreak, efficient human-to-human transmission has led to exponential growth of the virus, infecting millions of people. (1,4) The World Health Organization (WHO) declared a Public Health Emergency of International Concern (PHEIC) on 30 January 2020 and declared the outbreak a pandemic on 11 March 2020. (3,4) At the time of publication, SARS-CoV-2 has infected tens of millions of people across the globe, leading to more than 800,000 deaths worldwide.
The fight against a viral pandemic needs multipronged scientific approaches. The first requirement is the diagnostic detection of the virus. The development of fast and effective testing methods enables contact tracing and isolation of infected people, slowing the spread of the virus. Particularly with SARS-CoV-2, which spreads quickly through asymptomatic carriers, (5) large-scale testing is required to obtain a complete picture of viral spread. The testing methods must be accurate, suitable for mass production, inexpensive, and easy to deploy and use. Second, there is a need for therapeutic interventions that can effectively cure or reduce the effects of the virus. Therapeutics in the form of drugs and treatment strategies are essential to reduce the morbidity and mortality caused by the virus. Third, vaccines must be developed to help create antibodies, leading to eventual herd immunity. Vaccination has been able to eradicate various epidemic diseases, including smallpox, polio, and tuberculosis, in many countries. (6) However, the development of vaccines against most viral diseases has proven to be challenging. Researchers are yet to develop a vaccine for human immunodeficiency virus (HIV), which has caused over 40 million deaths to date. (7) Similarly, respiratory viral diseases (e.g., influenza) infect 3–5 million people and cause 290 000–650 000 deaths annually. (8) The 2003 SARS outbreak, which infected ∼8300 people with a mortality rate of ∼10%, eventually subsided in the summer, but there were no vaccines found at that time. (9) In 2012, the Middle East respiratory syndrome (MERS) virus affected at least 27 countries with a very high mortality rate of 35%. (10,11) Since then, much progress has been made in the field of vaccination against coronaviruses, the principles of which apply to SARS-CoV-2 as well. SARS-CoV-2 exhibits ∼80 and 50% similarity with the genomes of SARS-CoV and MERS-CoV, respectively. (12) All coronaviruses are zoonotic viruses, and similar to the 2003 SARS-CoV, SARS-CoV-2 also has a zoonotic origin, having emerged from bats. (9) SARS-Cov-2 has approximately 96% similarity to the bat coronavirus BatCoV RaTG13. (13)
SARS-CoV-2, a positive-sense single-stranded ribonucleic acid ((+)ssRNA) virus from the Coronaviridae family, is covered by an envelope with protein spikes. (12) As illustrated in Figure 1a, the four structural proteins of SARS-CoV-2 are spike surface glycoprotein (S), small envelope protein (E), matrix protein (M), and nucleocapsid protein (N). Official electron microscopy images released by the U.S. National Institute of Allergy and Infectious Diseases (NIAID), shown in Figures 1b–e, show the morphology and structure of SARS-CoV-2. SARS-CoV-2 particles have a diameter ranging from 60 to 140 nm. (12,14) Due to the particulate nature, morphology, and size domain of SARS-CoV-2, nanoparticle (NP)-based strategies present a powerful approach for tackling this virus. Recently, NPs have been widely used in many medical applications, such as biosensing, drug delivery, imaging, and antimicrobial treatment. (15−18) Various NPs have been shown to be effective tools for the detection and inhibition of and vaccination against coronaviruses. (19,20) This Review describes how we can build on the NP-based strategies used against viruses from the Coronaviridae family to develop tests, therapeutics, and vaccines to fight SARS-CoV-2.
Figure 1
Figure 1. (a) The SARS-CoV-2 structure is illustrated, with its structural viral proteins indicated. Reproduced with permission from ref (12). Copyright 2020 American Chemical Society. (b) Scanning electron microscopy (SEM) image showing the particulate nature of SARS-CoV-2 (yellow) isolated from a patient in the U.S., emerging from the surface of cells (pink) cultured in the laboratory. Image captured and colorized at NIAID’s Rocky Mountain Laboratories (RML) in Hamilton, Montana. Credit: NIAID-RML. (c–e) Transmission electron microscopy (TEM) images show SARS-CoV-2 isolated from a patient in the U.S. Virus particles are shown emerging from the surface of cells cultured in the laboratory. The crown-like spikes on the outer edge of the virus particles give coronaviruses their name. Image captured and colorized at NIAID’s RML in Hamilton, Montana. Credit: NIAID-RML.
2. Nanoparticles for Diagnostics
ARTICLE SECTIONS
Most viral RNA detection methods are based on the reverse transcription polymerase chain reaction (RT-PCR) due to its simplicity, high sensitivity, and high specificity based on the exponential increase in RNA produced during the operation. (21,22) Although RT-PCR methods are widely known as the standard methods for coronavirus detection, there are some limitations that need to be addressed, including low extraction efficiency, the use of time-consuming processes, and false positives caused by contamination. (23) Regarding the improvement of virus detection efficiency, due to their high surface area and ultrasmall size, NPs have been applied not only in RT-PCR methods but also other virus detection methods, such as an enzyme-linked immunosorbent assay (ELISA) and reverse transcription loop-mediated isothermal amplification (RT-LAMP). (24,25) Various kinds of NPs have been studied in the context of virus detection, including metal NPs, carbon nanotubes, silica NPs, quantum dots (QDs), and polymeric NPs. (20,26) Among them, metal NPs, metal nanoislands (NIs), magnetic NPs (MNPs), and QDs have been applied to coronavirus detection. Most of these diagnostic methods are based on colorimetric, electrochemical, fluorescence, and optical detection techniques. Table 1 provides a summary of the NPs used in the diagnostic detection of coronaviruses.
Table 1. Nanoparticles for Coronavirus Diagnostics
| NPs | conjugate | size (nm) | principles | detection techniques | virus | target molecules | detection limit [time] | key takeaways for COVID-19 | ref. |
|---|---|---|---|---|---|---|---|---|---|
| AuNPs | citrate ion | 13 | LSPR | colorimetric sensor | SARS | viral RNA | 4.3 nM [2 min] | aggregation of AuNPs by formation of dsDNA | (27) |
| citrate ion | 19 | LSPR | colorimetric sensor | MERS | viral RNA | 1 pmol/μL [10 min] | preventing aggregation of AuNPs by thiol–dsDNA | (28) | |
| streptavidin | - | LSPR and RT-LAMP | colorimetric sensor on strip | MERS | viral RNA | 1 × 101 copies/μL [35 min] | doubly labeled viral RNA amplicons binding to both AuNPs and antibody-coated detection strip | (29) | |
| ASOs | - | LSPR | colorimetric sensor | SARS-CoV-2 | N gene | 0.18 ng/μL [10 min] | aggregation of AuNPs induced by viral N-gene | (30) | |
| - | 50 | electronic | electrochemical immonosensor | HCoV, MERS | virus | 0.4 pg/mL, 1.0 pg/mL [20 min] | viral antigen immobilized to AuNP surface on electrodes | (31) | |
| AuNIs | - | 40 | PPT and PCR | gel electrophoresis | MERS | viral cDNA | 0.1 ng/μL [-] | ultrafast PCR for rapid cDNA amplification | (32) |
| - | - | LSPR and PPT | LSPR sensor | SARS-CoV-2 | viral RNA | 0.22 pM [-] | high selectivity to target virus, using cDNA receptors | (32) | |
| AgNPs | citrate ion | 19 | LSPR | colorimetric sensor | MERS, MTB, HPV | viral cDNA | 1.53 nM, 1.27 nM, 1.03 nM [-] | cDNAs preventing aggregation of AgNPs induced by acpcPNA | (33) |
| SMNPs | silica and oligonucleotide sequences | - | magnetic and PCR | fluorescent sensor | SARS | viral cDNA | 2.0 × 103 copies [6 h] | capturing and enriching viral target cDNA based on probe-functionalized MNPs | (34) |
| MNPs | PC | 10 | magnetic and RT-PCR | - | SARS-CoV-2 | viral RNA | 10 copies [30 min] | capturing and enriching viral target RNA based on probe-functionalized MNPs | (35) |
| QDs-605 | RNA aptamer | - | optical | fluorescent sensor | SARS | N protein | 0.1 pg/mL [1 h] | high sensitivity of immobilized target viral N protein | (36) |
| CdTe QDs and AuNPs | viral antibodies | 6–7 (QDs), 50 (AuNPs) | optical and LSPR | chiro-optical sensor | H5N1, H4N6, FAdVs-9 | viral recombinant protein | 1 pg/mL [-] | plasmon–exciton interaction of QDs and star-shaped AuNPs | (37) |
| ZrQDs and MPNPs | viral antibodies | 2–3 (QDs), 50 (MPNPs) | optical, LSPR, and magnetic | optical sensor | IBV | virus | 79 EID/50 μL [-] | combination of plasmon–exciton interaction with magnetic separation | (38) |
a
Abbreviations: LSPR: localized surface plasmon resonance, dsdna: double-stranded DNA, ASOs: antisense oligonucleotides, cDNA: complementary DNA, acpcPNA: pyrrolidinyl peptide nucleic acid, SMNPs: silica-coated superparamagnetic nanoparticles, PPT: plasmonic photothermal, PC: poly(amino ester) with carboxyl groups, MPNPs: magnetoplasmonic nanoparticles.
2.1. Metal Nanoparticles and Metal Nanoislands
Most metal NP-based virus detection techniques were designed based on the unique optical and electrical properties of metal NPs. In particular, noble metal NPs, such as gold, silver, and copper, have unique optical properties called localized surface plasmon resonance (LSPR). LSPR has been utilized in biosensing applications due to the tunable light absorption and scattering wavelength in the visible region. The change in the LSPR extinction maxima of metal NPs depends on the refractive index of the surrounding media and the degree of NP aggregation, which are important factors for the use of these NPs in biological applications. (39−41) Gold NPs (AuNPs) are the most common NPs used in diagnostic detection of viruses due to their unique optical properties, stability, and biocompatible properties. (42−44) Due to the LSPR effect, the aggregation of AuNPs causes a redshift in the LSPR peak position, resulting in an obvious change in the solution color from red to blue, which can be observed with the naked eye. This phenomenon is caused by the plasmonic coupling among the neighboring NPs when the colloidal NPs aggregate. (45)
The applications of AuNPs in virus detection have been reported. (42) AuNPs are also the most common metal NPs that have been used for coronavirus diagnostics. The use of AuNPs in colorimetric detection of SARS-CoV has been reported. (27) In this study, the difference in the electrostatic properties of single- and double-stranded DNA (ssDNA and dsDNA) was the foundation of the method. Specifically, ssDNA or ssRNA could interact with citrate ions on the surface of AuNPs and stabilize the particles even when salt was added into the solution, while the presence of dsDNA caused aggregation of AuNPs under the same conditions. Based on this finding, Li and Rothber designed a simple colorimetric hybridization assay to detect SARS-CoV based on the formation of dsDNA from viral ssRNA. (27) This colorimetric detection method confirmed the formation of dsDNA with a target concentration of 4.3 nM. Essentially, the results were observed within 10 min without the need for any complicated instrument. In a different approach, the formation of long dsDNA molecules from reactions of the target viral RNAs with a pair of thiol-functionalized probes showed the ability to stabilize AuNPs under positive electrolyte conditions. (28) In the presence of the target viral RNAs of MERS-CoV, the formation of disulfide bonds between the thiol-functionalized probes, which were designed to interact with target viral RNA, caused a self-assembly process to produce long thiol-modified dsDNA molecules on the gold surface. These monolayers of the long polymer-type structures of thiol-modified dsDNA on the surface prevented the AuNPs from aggregating under positive electrolyte conditions when MgCl2 was added into the solution (Figure 2a). On the other hand, the thiol-modified probes, without interaction with the target molecules, stayed on the AuNP surface in individual (monomeric) or dimeric molecules, formed via a disulfide formation reaction. Due to their short chain length, both monomers and dimers of the thiol-modified probes could not prevent the aggregation of AuNPs when salt was added, as shown in Figure 2b. This colorimetric reaction led to a change in the AuNP colloidal solution color in the presence of MERS-CoV at as low as 1 pmol/μL, and the detection process took only 10 min without additional procedures.
Figure 2
Figure 2. Colorimetric detection of RNAs based on a disulfide-induced self-assembly process. (a) Procedures for preventing salt-induced aggregation of AuNPs by disulfide-induced self-assembly of long thiol-modified dsDNAs in the presence of targets. (b) Salt-induced aggregation of AuNPs in the absence of targets. Adapted with permission from reference (28). Copyright 2019 American Chemical Society.
AuNPs can be further functionalized with biomolecules to modify their surface properties. For example, colloidal AuNPs conjugated with streptavidin were used for an RT-LAMP combined with a vertical flow visualization strip (RT-LAMP-VF) assay for MERS-CoV nucleic acid detection. (29) In this study, viral RNA was amplified by RT-LAMP, followed by a labeling process to form biotin/fluorescein isothiocyanate (FITC)-labeled amplicons. These amplicons can bind to streptavidin-functionalized AuNPs to generate a complex via biotin–streptavidin interactions. This complex showed color formation when captured by an anti-FITC antibody coated on the detection strip. The formation of the complex on the strip was visible to the naked eye within 35 min. The detection limit of this technique is equivalent to 10 copies/μL of MERS-CoV RNA. Moreover, the method showed high specificity for MERS-CoV without cross-reactivity with various other CoVs, such as HCoV-HKU1, HCoV-HKU4, SARS-CoV, HCoV-229E, and HCoV-OC43. Recently, designed thiol-modified antisense oligonucleotides (ASOs) were functionalized on AuNPs for colorimetric detection of the N gene (nucleocapsid phosphoprotein) of SARS-CoV-2. (30) Specifically, in the presence of the N gene of SARS-CoV-2, the thiol-modified ASO-capped AuNPs agglomerated, which caused a change in the color of the ASO-capped AuNP colloidal solution. Moreover, ribonuclease H (RNaseH) was added to the solution to cause visually detectable precipitation of agglomerated ASO-capped AuNPs. This method yielded the result within 10 min after the RNA isolation process. Additionally, the detection limit of this method was 0.18 ng/μL.
In addition to plasmon-based virus detection, AuNPs have been applied to electrochemical detection of coronaviruses. Layqah and Eissa reported the use of AuNPs to modify carbon array electrodes in electrochemical biosensors for both MERS-CoV and HCoV detection. (31) In this method, a viral antigen (recombinant spike protein S1 of MERS-CoV or Oc43 N of HCoV) is immobilized to the surface of AuNPs on the working electrodes. When a fixed amount of the corresponding viral antibody is added to the sample, the antibody binds to the immobilized antigen, decreasing the square wave voltammetry (SWV) reduction peak current. In the presence of virus, the change in current is different due to competition between the virus and immobilized antigen for binding to the antibody. Hence, the virus is detected based on the measured change in current in competitive immunoassays. The deposition of gold improves the electron transfer rate and increases the surface area of the electrode, resulting in high sensitivity of virus detection. (31) Specifically, this detection method was able to detect both MERS-CoV and HCoV with detection limits of 1.0 and 0.4 pg/mL, respectively. The detection process yielded results within 20 min. The method can be used for artificial nasal samples as well as to detect MERS-CoV and HCoV simultaneously.
Recently, Lee et al. developed a method for the detection of MERS-CoV based on nanoplasmonic on-chip PCR. (32) In this study, nanoplasmonic pillar arrays (NPAs) constructed from gold NIs (AuNIs) deposited on the top and side walls of glass nanopillar arrays were used to enhance the light absorption efficiency of the detection chip. Hence, ultrafast PCR thermal cycling was achieved via enhanced plasmonic photothermal heating generated via excitation of surface electrons of AuNIs by a white light-emitting diode (LED). When the LED was off, efficient heat diffusion through the NPAs allowed expeditious cooling of the PCR mixture. Consequently, this method required only 3 min and 30 s for rapid amplification of complementary DNA (cDNA) of MERS-CoV at a concentration of 0.1 ng/μL. However, the method could yield results very rapidly due to the use of gel electrophoresis for visualization of the amplicons of target viral cDNAs after the PCR. Interestingly, a faster detection technique was utilized by Wang and co-workers in a recently reported dual-function plasmonic photothermal biosensor for SARS-CoV-2 detection. (46) This biosensor combined the plasmonic photothermal (PPT) effect and LSPR biosensing technique for highly accurate detection of SARS-CoV-2 by targeting the viral RNA-dependent RNA polymerase (RdRp) sequence. Two-dimensional AuNIs (5.0–5.2 nm thick) were functionalized with thiol-modified cDNA receptors of viral gene sequences (RdRp-COVID or RdRp-SARS) to create microfluidic LSPR sensor chips (Figure 3a). Localized thermoplasmonic heating significantly improved the hybridization speed of viral gene sequence targets with their cDNA receptors immobilized on the sensor chips, enhancing the sensing performance. Importantly, this sensor can distinguish SARS-CoV and SARS-CoV-2 due to the partial mismatch between the sequences of the SARS-CoV and SARS-CoV-2 cDNA receptors, as shown in Figure 3b,c. (46) This method exhibited high sensitivity toward SARS-CoV-2 sequences at a concentration of 0.22 pM.
Figure 3
Figure 3. Schematic illustrations of (a) cDNA-receptor-functionalized AuNI based on the reaction with thiol–cDNA ligands, (b) the hybridization of two complementary strands, and (c) the hybridization of two partially matched sequences. Adapted with permission from reference (46). Copyright 2020 American Chemical Society.
Although AuNPs are the most common metal NPs used in virus detection, several studies have suggested the use of other metal NPs. Silver NPs (AgNPs) have been used in paper-based analytical devices (PADs) for MERS-CoV detection. (33) The device can also be applied in the diagnosis of other bacteria and viruses, such as Mycobacterium tuberculosis (MTB) and human papillomavirus (HPV). In this study, the authors used pyrrolidinyl peptide nucleic acid (acpcPNA)-induced aggregation of AgNPs to design a colorimetric assay. Specifically, the cationic acpcPNA probes can bind to negative citrate ions on the surface of AgNPs, inducing NP aggregation together with a change in color. On the other hand, in the presence of viral target cDNAs, acpcPNAs preferred to interact with the target cDNAs to form dsDNAs and stayed separate from AgNPs in the solution, leading to no significant color change. (33) The paper-based device exhibited high sensitivity, with detection limits of 1.53, 1.27, and 1.03 nM for MERS-CoV, MTB, and HPV, respectively.
2.2. Magnetic Nanoparticles
Magnetic NPs (MNPs) play an important role in the separation of viral RNA from solution before the diagnosis process. (47,48) The most common MNPs that have drawn attention in the biological application field are iron oxide NPs due to their high magnetic efficiency and simple synthesis approaches. (49,50) Regarding coronavirus detection, Gong et al. used silica-coated superparamagnetic NPs (SMNPs) in PCR-based assays to improve the selectivity of the target cDNA of SARS-CoV in the separation process. (34) Specifically, silica-coated SMNPs were conjugated with oligonucleotide probes for capturing viral target cDNAs to produce magnetic-conjugated dsDNA complexes. The magnetic-conjugated dsDNA was separated from other components by using simple magnetic separation before dehybridization to form enriched cDNAs. (34) The viral enriched cDNA was amplified through PCR followed by isolation via another magnetic separation step. The amplified viral target cDNA was detected by a sandwich hybridization assay with silica-coated fluorescent NP (SFNP)-based signaling probes. The technique can detect the target cDNA with a detection limit of 2.0 × 103 copies within 6 h.
Recently, MNPs have been applied to SARS-CoV-2 detection. Several studies have reported the use of iron oxide coated with silica for RNA extraction from patient samples. (51,52) Furthermore, other functional groups have been reported to have strong affinity for viral RNAs. Zhou, Yu, and co-workers reported a viral RNA extraction method using poly(amino ester) with carboxyl group (PC)-coated MNPs (pcMNPs). (35) SARS-CoV-2 RNA was captured and enriched by pcMNPs to produce pcMNP–RNA complexes. Due to the magnetic property of pcMNPs, the pcMNP–RNA complexes were easily extracted from the solution by applying an external magnetic force. Interestingly, the pcMNP–RNA complexes can be immediately used in the following RT-PCR process for viral RNA amplification without the use of an elution step. The pcMNP-based extraction method exhibited high purity and high productivity within 30 min. In addition, the pcMNPs showed good binding with viral RNA, resulting in 10-copy sensitivity using the RT-PCR-based detection technique.
2.3. Quantum Dots
Due to their unique optical and electrical properties, QDs have been applied in the detection of several viruses. (53,54) For coronavirus detection, a QD-conjugated RNA aptamer specific to the SARS-CoV N protein has been reported to have high sensitivity in recognizing immobilized viral protein on designed chips. (36) The authors used commercially available QD-605 with an emission maximum at 605 nm to obtain an outstanding detection limit for the SARS-CoV N protein at 0.1 pg/mL by detecting the fluorescent emission intensity measured by confocal laser scanning microscopy. (36)
The nanohybrid structures of QDs and other NPs have also been reported for coronavirus detection. Because of their extraordinary plasmonic properties, star-shaped chiroplasmonic AuNPs were combined with CdTe QDs to construct a chiral optical biosensor. (37) Two influenza virus antibodies named anti-HA and anti-NA were immobilized on the surfaces of the star-shaped gold NPs and CdTe QDs, respectively. When a recombinant protein of influenza A (H5N1) was present in the same solution containing both anti-HA-conjugated AuNPs and anti-NA-conjugated QDs, AuNP–QD nanohybrids were formed through antigen–antibody interactions (immunolinking) of the recombinant protein with the two antibodies immobilized on the surfaces of the NPs and QDs. The plasmon–exciton interaction in the newly created AuNP–QD nanohybrids significantly enhanced the chiral optical response of the solution. Consequently, the viral recombinant protein was detected based on the measured circular dichroism response of the solution. In this technique, star-shaped AuNPs were chosen due to their broad plasmonic peak at 590 nm that maximizes the optical coupling and overlaps with the QD excitonic wavelength. The method showed sensitivity at 1 pg/mL for H5N1 detection and was able to detect several other viruses in blood samples, such as avian influenza A (H4N6) virus, fowl adenovirus, and coronavirus. (37) In 2018, a similar approach was used by the same research group to develop a magnetoplasmonic–fluorescent biosensor based on zirconium QDs (ZrQDs) and Fe3O4@Au core–shell magnetoplasmonic NPs (MPNPs). As shown in Figure 4, two types of particles were functionalized with viral antibodies. The viral antibody-functionalized NPs stayed apart from each other in the solution. After the target virus was added to the system, the conjugated ZrQDs and MPNPs formed magnetoplasmonic–fluorescent nanohybrid structures via immunolinking. Hence, the detection of the target virus was based on the photoluminescence (PL) properties of the ZrQD–Fe3O4@Au MPNP nanohybrids after simple magnetic separation. The nanohybrid structures also showed a change in photoluminescence emission intensity with a change in virus concentration in the system. (38) The method can selectively detect the presence of infectious bronchitis virus (IBV) at a concentration of 79.15 EID/50 μL in blood medium.
Figure 4
Figure 4. Schematic illustration of the formation of ZrQDs and Fe3O4@Au MPNP nanohybrid structures for magnetoplasmonic–fluorescent virus detection. Adapted with permission from reference (38). Copyright 2018 Elsevier.
3. Nanoparticles for Therapeutics
ARTICLE SECTIONS
Much is still unknown about SARS-CoV-2, but it has been determined to be an enveloped virus with spike proteins as the main cell-infecting sites and an ssRNA as the genetic material. Many viruses investigated in NP-based antiviral research are from the coronavirus family or share a similar structure with SARS-CoV-2. NP-based therapeutic drugs can inhibit the effects of viral infection in several ways, including by blocking receptor binding and cell entry, blocking viral replication and proliferation, and directly inactivating the virus. These therapeutic strategies are discussed in this section. Table 2 lists the NPs that can be used for therapeutic strategies against coronavirus infections together with the key takeaways that can be applied for COVID-19.
Table 2. Nanoparticles for Therapeutics
| NPs | conjugate | size (nm) | cytotoxicity (dose, time) | virus | approach | level of study | key takeaways for COVID-19 | ref. |
|---|---|---|---|---|---|---|---|---|
| AuNPs | sialic acid | 14 | 99% cell viability | IAV | infection inhibition | in vitro | 40% infection reduction | (55) |
| MES | 4 ± 1 | - | IAVs | infection inhibition | in vitro | 80% infection reduction | (56) | |
| MES/MUS-OT | 2.5 ± 0.7 | noncytotoxic | RSV, VSV, HPV, dengue | viricidal therapy | in vivo/ex vivo | permanent damage of up to 87% virus, no lung damage | (57) | |
| porous AuNPs | - | 154 ± 37 | 95% cell viability (0.2 mg/mL, 24 h) | H1N1, H3N2, H9N2 | infection inhibition | in vitro | 96.8% survival rate of infected cell | (58) |
| AuNRs | PH peptide + PEG | 54:18 | no cytotoxicity | MERS | block viral entry | in vivo | PIH–AuNRs are 10-fold better than PIH; inhibit 90% cell fusion, AuNRs improve biostability | (59) |
| AgNPs | curcumin | 20 | cell viability >95% (0.24 nM, 72 h) | RSV | block viral entry | in vitro | cAgNPs directly interfere with virus, curcumin reduces AgNP toxicity | (60) |
| graphene oxide | <10 | cell viability >90% (1.5625 mg/mL, 24 h) | FCoV | block viral entry | in vitro | graphene oxide becomes effective against enveloped viruses on coupling with AgNPs | (61) | |
| - | <20 | >80% cells unaffected (12.5 μg/mL, 48 h) | TGEV-CoV | replication/infection inhibition | in vitro | 67.35% virus reduction | (62) | |
| oseltamivir | 3 | - | H1N1 | infection & apoptosis inhibition | in vitro | 90% infected cell viability | (63) | |
| zanamivir | 3 | - | H1N1 | infection & apoptosis inhibition | in vitro | 82% infected cell viability | (64) | |
| - | 10 | minor mucosal thickening | RSV | replication inhibition | in vitro/in vivo | 79% replication reduction, no illness in mice | (65) | |
| SiNPs | 5–50 | no cytotoxicity | HIV, RSV | block viral entry | in vitro | effective against enveloped viruses, biodegradable | (66) | |
| SeNPs | zanamivir | 82 | - | H1N1 | infection inhibition | in vitro | 73% infected cell viability | (67) |
| amantadine | 70 | - | H1N1 | infection & apoptosis inhibition | in vitro | 79% infected cell viability | (68) | |
| ribavirin | 65 | - | H1N1 | infection & apoptosis inhibition | in vitro/in vivo | 81% infected cell viability, lungs protected | (69) | |
| oseltamivir | 100 | - | H1N1 | infection inhibition | in vitro | 93% infected cell viability | (70) | |
| ZnO NPs | PEG | 18 | >90% cell viability (0.2 mg/mL, 24 h) | H1N1 | viral inactivation | in vitro | 90% infected cell viability | (71) |
| SiO2NPs | GPTMS, APTES, TMPES | 354 | 65% cell viability (0.1 mg/mL, 48 h) | HIV, VSV | infection inhibition | in vitro | 50% infection reduction | (72) |
| Fe3O4@SiO2 | biguanide, polymeric aziridine | 150 | >80% cell viability (0.2 mg/mL, 5 h) | HSV | viral inactivation | in vitro | 50-fold antiviral improvement effect on antiviral conjugates | (73) |
| Ag2S | glutathione | 4.1 ± 1.5 | >90% cell viability (46 μg/mL, 48 h) | PEDV-CoV model | replication inhibition/immunity activation | in vitro | viral titer reduced 1000 times | (74) |
| CDs | R-B(OH)2, NH2 | 9.2 ± 0.3 | nontoxic at 100 μg/mL, 24 h | HCoV-229E | block viral entry and viral replication | in vitro | inhibition of cell entry with CDs enhanced by boronic acid | (75) |
| - | 1.5 | >90% cell viability (125 μg/mL, 48 h) | PEDV-coronavirus model | replication inhibition/immunity activation | in vitro | 80% viral reduction | (76) | |
| - | 11.4 | noncytotoxic (0.3 mg/mL, 24 h) | PRRSV-CoV model | viral inactivation | in vitro | 10-fold viral reduction | (77) | |
| - | 4.4 ± 0.6 | - | Zika, dengue | infection inhibition | in vitro | 90% infected cell viability | (78) | |
| cellulose nanocrystals | tyrosine sulfate | 113 | >80% cell viability (−) | Alphavirus | infection inhibition | in vitro | 100% infection inhibition | (79) |
| PLA NPs | chloroquine | <300 | Cell viability ≥70% (30 μg/mL, 48 h) | HSV-1 | block viral entry | in vitro | slow and targeted release of chloroquine with PLA NPs, which also reduces chloroquine toxicity. PLA is biodegradable | (80) |
| lipid nanodiscs | sialic acid | 15 | - | H1N1 | viral inactivation | in vitro/in vivo | 60% infection reduction, 40% death rate reduction in mice | (81) |
a
Abbreviations: PLA: poly(lactic) acid, HSV: herpes simplex virus, CDs: carbon dots, RSV: respiratory syncytial virus, FCoV: feline coronavirus, cAgNPs: curcumin-modified Ag nanoparticles, HIV: human immunodeficiency virus, MES: 3-mercaptoethylsulfonate, MUS: undecanesulfonic acid, OT: 1-octanethiol, APTES: (3-aminopropyl)triethoxysilane, GPTMS: (3-glycidyloxypropyl)trimethoxysilane, TMPES: trimethoxy-(2-phenylethyl)silane, VSV: vesicular stomatitis virus, HPV: human papillomavirus, PEDV: porcine epidemic diarrhea virus, TGEV: transmissible gastroenteritis coronavirus, IAV: influenza A virus.
3.1. Nanoparticles That Block Cell Attachment and Viral Entry
Viral infections start with the binding of viral particles to receptors on the host cells, followed by the entry of the virus into the cells. In the case of SARS-CoV-2, the spike S glycoprotein is responsible for cell binding and entry. (82,83) As illustrated in Figure 5a, the S protein of SARS-CoV-2 can be divided into two subunits: the S1 subunit is responsible for attachment, while the S2 subunit mediates membrane fusion and entry into the cell. (82,84) The S1 subunit consists of an N-terminal domain (NTD) and a C-domain; the S2 subunit consists of a potential fusion peptide (pFP), heptad repeats N and C (HR-N, HR-C), and a transmembrane domain (TM). The S1 protein has been shown to bind specifically to the human angiotensin-converting enzyme 2 (ACE2) receptor on the surface of human cells. (13,82) Membrane fusion of the attached virus mostly occurs via endocytosis. (13,83) Therefore, blocking the mechanism by which the virus binds to the ACE2 receptor or blocking viral endocytosis is a potent strategy for drug development and treatment. One of the drugs being widely considered for this purpose is chloroquine. Chloroquine has been shown to inhibit endocytosis of NPs in general; since SARS-CoV-2 is morphologically similar to NPs, chloroquine can block the endocytosis of SARS-CoV-2 virus particles as well, as illustrated in Figure 5b. (85) The proposed mechanism involves chloroquine-induced suppression of PICALM, which prevents endocytosis-mediated uptake of NPs, including SARS-CoV-2. Although chloroquine blocks NP endocytosis into the cell, the efficacy of chloroquine depends on its delivery and cellular uptake, which can be greatly aided by encapsulating the molecule inside polymeric NPs. The most commonly used NPs for encapsulating chloroquine are poly(lactic acid) (PLA) polymeric NPs. (80)
Figure 5
Figure 5. (a) Diagram of full-length SARS-CoV-2 S protein with a 3xFLAG tag. S1: receptor-binding subunit; S2: membrane fusion subunit; TM: transmembrane domain; NTD: N-terminal domain; pFP: potential fusion peptide; HR-N: heptad repeat-N; HR-C: heptad repeat-C. Reproduced with permission from ref (83). Copyright 2020 Springer Nature. (b) Potential mechanism by which chloroquine exerts therapeutic effects against COVID-19. The proposed mechanism involves chloroquine-induced suppression of PICALM, which prevents endocytosis-mediated uptake of nanoparticles, including SARS-CoV-2. Adapted with permission from ref (85). Copyright 2020 Springer Nature.
In addition to facilitating drug delivery, NPs can also directly interfere with receptor binding and cell entry of viruses. Ting et al. demonstrated that ∼1.6 nm cationic carbon dots (CDs) synthesized from curcumin (CCM-CDs) can block viral entry of porcine epidemic diarrhea virus (PEDV), a coronavirus model. (76) The inhibition efficiency was over 50% at 125 μg/mL, blocking viral entry at an early stage (see Figure 6a). The blocking is most likely caused by electrostatic interactions between the cationic CDs and the negatively charged PEDV, which neutralizes the effective charge on the virus particles, leading to virus aggregation, as seen from the zeta potential data in Figure 6b. The CDs also suppressed the accumulation of reactive oxygen species (ROS), reducing cell apoptosis. Curcumin can also act as a reducing and capping agent in the synthesis of curcumin-modified AgNPs (cAgNPs), which have also been shown to inhibit cell entry of respiratory viruses. (60) For this purpose, smaller cAgNPs with large surface areas are seen to be more effective than larger NPs. Interestingly, smaller cAgNPs are also less cytotoxic than larger NPs. (60) The driving force behind this process is the same as that for “protein corona” formation; high surface areas of small AgNPs lead to direct interactions with the viral envelope proteins and greater inhibition. (60) Graphene QDs have also been found to be effective in interfering with cell binding of HIV, (86) while AgNPs coupled with graphene oxide (GO) sheets have been shown to be effective in blocking cell entry of feline coronavirus (FCoV) and enveloped viruses. (61) Moreover, various surface-functionalized AgNPs and AuNPs have also been shown to be effective in blocking cell entry of HIV and herpes simplex virus (HSV). (87) The advantage of AuNPs is that they are less cytotoxic than AgNPs. (88−90)
Figure 6
Figure 6. (a) Dose relationship between the viral entry inhibitory efficiency and amount of added CCM-CDs. (b) Zeta potentials of CCM-CDs, PEDV, and CCM-CDs pretreated with PEDV, indicating aggregation of PEDV upon treatment with CDs. Reproduced with permission from ref (76). Copyright 2018 American Chemical Society.
In addition to virus aggregation, AuNPs can also directly interfere with the cell entry mechanism, as demonstrated by Huang et al. (59) Similar to the SARS-CoV-2 S2 subunit shown in Figure 5a, the S2 protein of MERS-CoV contains heptad repeat 1 (HR1), heptad repeat 2 (HR2), and a fusion protein (FP). As illustrated in Figure 7a, after the FP inserts into the cell membrane, HR1 and HR2 bind to form a six-helix bundle (6-HB). The 6-HB pulls together the MERS-CoV envelope and host cell membrane, promoting fusion. Huang et al. identified a peptide, named pregnancy-induced hypertension (PIH), which could mimic the conformation of HR2. Thus, this peptide can interact with HR1 to block the formation of 6-HB, inhibiting the cell fusion process. When PIH was immobilized on the surface of gold nanorods (PIH–AuNRs), a 10-fold higher inhibitory activity was observed that could completely block cell fusion at the optimized concentration (see Figure 7c,d). The PIH–AuNRs also demonstrated excellent biocompatibility (see Figure 7b).
Figure 7
Figure 7. (a) Schematic diagram of the inhibition of MERS-CoV S2-subunit-mediated membrane fusion with an HR1 inhibitor (left); the HR1 inhibitor can inhibit HR1/HR2 complex (6-HB)-mediated membrane fusion and prevent MERS-CoV infection (right). (b) Body weights of mice in both the PIH–AuNR group and control group steadily increased, demonstrating excellent biosafety of PIH–AuNRs. (c) Quantification of cell fusion in the presence of PIH, AuNRs, and PIH–AuNRs. (d) Inhibitory effect of PIH–AuNRs on MERS-CoV S2-subunit-mediated cell fusion, indicating that PIH–AuNRs are more potent anti-MERS agents than the peptide PIH. Reproduced with permission from ref (59). Copyright 2019 American Chemical Society.
In addition to AuNPs, other NPs have also been shown to be effective at blocking viral entry while maintaining low toxicity. Among synthetic NPs, porous silicon NPs (SiNPs) are especially favored due to their extreme biocompatibility. SiNPs are biodegradable, since they gradually dissolve in water to form nontoxic silicic acid. (66) Osiminka et al. showed that SiNPs were able to act as scavengers of free virus particles and prevented them from infecting host cells. Binding of SiNPs with virions is universal for different enveloped viruses, making them potential agents against SARS-CoV-2 as well. (66) Mesoporous-SiO2 (mSiO2) NPs, when functionalized with various moieties, exhibit the ability to attach themselves to enveloped viruses via hydrophobic/hydrophilic interactions. Strong bonds between the functionalized mSiO2 NPs and the virus disturb the virus’s attachment to host cell receptors and reduce viral entry into the cells. (72) Other types of biocompatible NPs known for inhibiting cellular entry of viruses include selenium NPs (SeNPs). Selenium is biocompatible, being present in several selenoproteins that are crucial for biological processes, and exhibits antiviral effects at high concentrations. (91) The antiviral activity of SeNPs can be further amplified when these NPs are combined with the antiviral drug Arbidol (ARB), effectively blocking cell entry of influenza virus and reducing cell apoptosis. Cationic chitosan, a nontoxic polysaccharide, has also shown the ability to interact with the S protein of various human coronaviruses and block their interaction with the ACE2 receptor. (92) Raghuwanshi et al. utilized cationic chitosan NPs functionalized with targeted antibodies for efficient delivery of a vaccine to dendritic cells (DCs) via the intranasal route, but these NPs have potential for use as DC-targeting drugs for blocking viral entry as well. (93)
3.2. Nanoparticles That Block Viral Replication and Proliferation
For viral infection, therapeutics that inhibit the proliferation speed or infectivity of viruses are of paramount importance. These treatments will keep the virus level in the body low enough for the immune system to respond effectively and in a timely manner as the first line of defense as well as to limit the virus’s capability to resist treatment via genetic mutation. Due to multiple outbreaks, respiratory diseases caused by members of the coronavirus family have received much research attention over the past decade for the development of effective therapies. Various NPs have been investigated as antiviral agents for inhibition of viral proliferation.
The infectivity of the transmissible gastroenteritis virus (TGEV), a member of the coronavirus family, is significantly diminished in the presence of AgNPs and silver nanowires (AgNWs) at concentrations below the toxic level. (62) Silver nanostructures have also been demonstrated to decrease cell apoptosis induced by viral infection. Data have suggested that Ag nanomaterials regulate p38-MAPK-p53 mitochondrial signaling cascades by inhibiting TGEV-induced expression of the Pi-p38 protein. This regulation reduces cell apoptosis induced by TGEV infection.
PEDV is a commonly studied model virus of the coronavirus family due to its high similarity to other human-infecting coronaviruses and the economic impact caused by PEDV infection. Han and co-workers reported the suppression of PEDV infection by 3 orders of magnitude via treatment with glutathione-capped Ag2S nanoclusters (Ag2S NCs). (74) The study also pointed out that the mechanisms of inhibition of viral proliferation are based on the suppression of RNA synthesis, as shown in Figure 8. The authors further found that Ag2S NCs activated the generation of interferon (IFN)-stimulating genes (ISGs) and cytokine expression, which further inhibited viral infection.
Figure 8
Figure 8. Possible mechanisms of the antiviral activity of Ag2S NCs via inhibition of the synthesis of viral RNA and viral budding due to the production of ISGs and upregulation of proinflammatory cytokines. Reproduced with permission from ref (74). Copyright 2018 American Chemical Society.
In addition to members of the coronavirus group, there are various viruses with structures similar to that of SARS-CoV-2 with positive-sense ssRNA genetic material, an envelope of phospholipids, and proteins. Many of these viruses have even been used as models for coronavirus research in recent years, and the efficacy of nanoparticles on these viruses could be relevant to therapy development for SARS-CoV-2. As one of the most heavily studied viruses due to multiple global pandemics in the last 100 years, influenza A viruses with their frequent genetic mutation and increasing resistance to drugs have been the target for various NP-based therapeutic research efforts. A potentially effective therapeutic target of many influenza viruses is hemagglutinin (HA), a highly conserved surface protein possessing six disulfide bonds. Haam and co-workers used porous gold NPs (PoGNPs) to target the HA protein on various influenza viruses based on strong gold–thiol interactions. (58) The results demonstrated significant inhibition of viral infectivity in cells treated with PoGNPs, and the cell viability increased to 96.8%, compared to 33.9% of nontreated cells. The viral inhibition efficacy was confirmed on the H1N1, H3N2, and H9N2 viruses to demonstrate the universal effectiveness of the approach. The biocompatibility of PoGNPs was also evaluated by the WST-1 assay, showing 95% cell viability. Alghrair et al. reported that AgNPs and AuNPs functionalized with FluPep, a peptide that can effectively inhibit influenza A viruses (IAVs), showed greater antiviral activity than free FluPep. (94) Haag and co-workers used electron microscopy imaging to visually show that AuNPs functionalized with sialic-acid-terminated glycerol dendrons specifically targeted the viral HA protein to effectively inhibit viral proliferation. (55) Moreover, various NPs, such as oseltamivir-functionalized AgNPs, (63) AgNP/chitosan composites, (95) zanamivir-functionalized AgNPs, (64) zanamivir-functionalized SeNPs (through the p38 and JNK signaling pathways), (67) amantadine-functionalized SeNPs (through the ROS-mediated AKT signaling pathways), (68) ribavirin-functionalized SeNPs (via the caspase-3 apoptotic pathway), (69) oseltamivir-functionalized SeNPs, (70) PEGylated-ZnO NPs, (71) and anionic AuNPs, (56) have also been fabricated and investigated for inhibitory effects on and biocompatibility with H1N1, a current seasonal virus that caused two deadly global pandemics in 1918 and 2009.
In addition to influenza viruses, porcine reproductive and respiratory syndrome virus (PRRSV), a model virus often used for coronavirus research, has also been reported to be highly suppressed after exposure to AgNP-modified GO (GO–AgNPs) with 59.2% inhibitory efficiency. (96) GO–AgNP nanocomposite treatment also enhanced the production of IFN-α and ISGs, which can directly inhibit viral proliferation. In another study, Tong et al. reported the synthesis of glycyrrhizic-acid-based CDs (Gly-CDs) and their high inhibitory activity of up to 5 orders of viral titers through multisite inhibition of PRRSV. (77) The multisite viral inhibitory mechanisms of Gly-CDs include inhibition of viral invasion and replication, stimulation of IFN production in cells, and inhibition of viral-infection-induced ROS production, providing a promising alternative for coronavirus infection therapy as well as PRRSV infection therapy. This work also showed the remarkable ability of Gly-CDs to suppress PEDV and pseudorabies virus (PRV), suggesting a broad antiviral capability compared to previous work. (97) These results on model viruses might serve as guides for research and development on SARS-CoV-2.
The infection caused by Zika virus, a virus with a similar structure to coronaviruses and the cause of a widespread epidemic in South and North America in 2015, was suppressed by benzoxamine-monomer-derived CDs (BZM-CDs). (78) The data from a plaque uniform assay and transmission electron microscopy (TEM) showed that BZM-CDs could reduce viral infectivity via direct interaction with the viruses. The inhibitory ability of BZM-CDs was also demonstrated on Japanese encephalitis and dengue viruses, two other life-threatening viruses that also exhibit structural similarity to coronaviruses, as well as on nonenveloped viruses (e.g., adeno-associated virus (AAV), porcine parvovirus (PPV)), suggesting that the broad-spectrum potential of the NPs should be further investigated for SARS-CoV-2.
Alphaviruses, a genus of RNA viruses with a structure similar to that of coronaviruses, were strongly inhibited in Vero (B) cells by cellulose nanocrystals (CNCs) modified with tyrosine sulfate mimetic ligands, while no observable cytotoxicity in human cells was detected. (79) The incorporation of tyrosine sulfate mimetic ligands on CNCs led to increased viral inhibition compared to incorporation of the control CNCs. This discovery suggests potential applications of CNCs for the treatment of HIV and HPV. In addition, studies of NP-based antiviral treatment of viruses similar to SARS-CoV-2 were also reported for AgNPs with Chikungunya virus (CHIKV) and respiratory virus (RSV), (65,98) cAgNPs with RSV, (99) and SiNPs with RSV. (66)
In the coronavirus family, the outer envelope with the surface proteins is vitally important to the infection and proliferation of the virus. Various studies have reported the remarkable efficacy of NP-based inhibition of HIV by targeting the viral outer envelope using AgNPs, (100) AuNPs, (101−103) porous SiNPs, (66) and silica NPs. (72) Human-related enveloped viruses such as vesicular stomatitis virus (VSV), tacaribe virus, PRV, and HSV have also been shown to be significantly inhibited by silica NPs, (72) AgNPs, (104) CDs, (97) and modified AgNPs, (105−107) respectively. These NP-based antiviral therapies targeting the outer envelopes of enveloped viruses are very relevant to further studies on SARS-CoV-2.
3.3. Nanoparticles for Viral Inactivation and Viricidal Treatment
Instead of inhibiting the cell–virion interaction, genetic material replication, or release of newly formed virions, another strategy to halt viral infection is inactivation or destruction of the virus itself. In an elegant study led by Stellacci, AuNPs coated with 3-mercaptoethylsulfonate (MES) showed viral infection inhibition at a concentration corresponding to the EC90, but the viral infectivity was fully recovered upon dilution. This process is called reversible viral inhibition and is similar to the effect of heparin, a common virustatic material that targets virus–cell interactions. Interestingly, the authors found that when MES was substituted by a 2:1 mixture of undecanesulfonic acid (MUS) and 1-octanethiol (OT), the MUS:OT–AuNPs could induce irreversible viral inactivation of various human-infecting viruses, ranging from HSV, VSV, RSV, and dengue virus to HPV and lentivirus. (57) The MUS ligand has a long and flexible hydrophobic backbone terminated with sulfonic acid mimicking the heparin sulfate proteoglycan (HSPG), a common and highly conserved target of viral attachment ligands, allowing effective virus–NP binding. This strong binding force (∼190 pN) led to irreversible deformation of the virus, as shown in Figure 9. The strong viral–MUS:OT–AuNP binding was further confirmed by electron microscopy imaging and molecular dynamics simulation. Moreover, an in vivo test in mice and an ex vivo test in human cervicovaginal histocultures also demonstrated the viral inactivation activity of the MUS:OT–AuNPs, with no cytotoxicity observed. This strategy is intrinsically broad spectrum, allowing viricidal treatment of multiple viruses. The viruses used in the study were very similar to coronaviruses, suggesting the potential applicability of the method for SARS-CoV-2.
Figure 9
Figure 9. (a) Viricidal activity of AuNPs coated with MES or MUS. (b) Heparin, MES-coated AuNP, and MUS:OT-coated AuNP viral infectivity curves (blue) and viricidal assays at concentrations corresponding to the EC90 (black) and after dilution (red). (c) Viricidal activity of MUS:OT-coated AuNPs against HPV, RSV, VSV (indicated as LV), and dengue virus (DENV-2). (d) MUS:OT-coated AuNP-mediated inhibition of viral infectivity against HSV-2 versus time (min). Reproduced and adapted with permission from ref (57). Copyright 2017 Springer Nature.
In another study, Kong et al. showed that decoy virus receptor-functionalized nanodiscs, self-assembled discoidal phospholipid bilayers wrapped in amphipathic membrane scaffold proteins, can inactivate the H1N1 virus by selectively targeting the virion’s surface proteins to cause irreversible physical damage to the envelope. (81) The antiviral activity of the viral decoy molecule sialic acid was amplified after grafting onto the nanodiscs due to the enabling of multivalent interactions with viral target proteins. The data also showed that the presence of the functionalized nanodiscs led the virus to self-disrupt its envelope with its own fusion machinery. The strength of this method is the use of biocompatible NPs and viral decoy molecules, making it a compelling method for in vivo studies. Gao and co-workers recently showed the catalytic inactivation of iron oxide (Fe3O4) NPs targeting the viral envelopes on 12 different subtypes (H1–H12) of IAVs. (108) The ferromagnetic Fe3O4 NPs with an average diameter of 200 nm were named iron oxide nanozymes (IONzymes) due to their unique enzyme-like property, catalyzing peroxidase and catalase reactions. Consequently, IONzymes could strongly induce lipid peroxidation in the viral envelope and destroy the integrity of viral surface proteins, including HA, neuraminidase, and matrix protein I, leading to inactivation of the viruses. Additionally, the authors loaded the IONzymes on facemasks and observed good protection against multiple strains of IAVs, including H1N1, H5N1, and H7N9. The biocompatibility and simple synthesis of the IONzyme nanomaterial make it attractive for effective and safe early stage antiviral therapeutics. Thus, the IONzyme nanomaterials present a potentially powerful approach against SARS-CoV-2.
In addition to the works highlighted above, other studies also reported promising inactivation and viricidal effects of different NPs on many viruses that share structural similarities with SARS-CoV-2. Among those reports are the inhibition of dengue virus by photosensitizer-carrying upconversion NPs, which can convert low-energy photons to high-energy photons; (109) inhibition of the measles virus by AuNPs synthesized by using Allium sativa (garlic extract) as a reducing agent; (110) inhibition of hepatitis C virus by AuNP-based nanozymes; (111) inhibition of HSV by poly(hexamethylene biguanide) (PHMBG) or aziridine-terminated polyethylenimine-functionalized superparamagnetic iron oxide@silica core–shell NPs; (73) inhibition of IAVs by AgNP-decorated silica particles; (112) inhibition of H1N1 virus by didodecyldimethylammonium bromide-coated silica NPs, (113) HIV by AgNPs; (114) peptide triazole Env inhibitor-conjugated AuNPs; (103) and T-cell-mimicking NPs based on poly(dl-lactide-coglycolide) NP cores. (115)
3.4. Nanoparticles Combining Multiple Approaches for Treatment
In addition to NPs that employ one of the three methods mentioned above to treat viral infection, various works have also shown NPs that can attack viruses via a combination of approaches. Nanoparticles that can inhibit the viruses via multiple mechanisms offer more effective opportunities for reducing viral infection through synergetic effects. Recently, Szunerits and co-workers modified carbon QDs (CQDs) of different sizes in the range of 4.5–8 nm with various functional groups, including NH2, COO–, N3, triazole, R-B(OH)2, and PEG, for human coronavirus (HCoV) therapy. (75) Biocompatible QCDs functionalized with triazole, boronic acid, and amino groups showed significant inhibition of HCoV infection in a concentration-correlated manner. Mechanistic studies by the authors suggested that the particles not only interfere with the replication of HCoV but also inhibit the interaction of the surface S protein with the host cell and therefore interrupt the cell fusion of HCoV as shown in Figure 10. Rather than interacting with viral proteins, these CDs interfere with the cellular mechanism for S protein attachment and viral uptake. This work demonstrated highly promising antiviral agents based on biocompatible NPs, which should be further investigated for their activity against SARS-CoV-2, which is also an HCoV with the S protein as the main cell-infecting site.
Figure 10
Figure 10. (a) Effect of CQD on HCoV by inhibition of S protein–receptor interaction (top) and viral RNA genome replication (bottom). (b) Viral inhibition using CQDs-3, CQDs-5, and CQDs-6. Reproduced and adapted with permission from ref (75). Copyright 2019 American Chemical Society.
PRRSV, a model virus for coronavirus studies, has been shown to be directly inactivated and entry-blocked by glutathione-stabilized fluorescent gold nanoclusters (AuNCs). (116) Immunofluorescence assay, Western blot assay, plaque assay, and RT-qPCR assay data indicated that viral proliferation and protein expression were inhibited by AuNCs. The functionalized AuNCs in this study showed low biocompatibility and therefore may not be suitable for in vivo application. However, the coupling of AuNCs with other suitable biocompatible virus-targeting agents could lead to effective virus inactivation.
4. Nanoparticles as Immunogenic Agents for Vaccines
ARTICLE SECTIONS
The most effective way to fight a viral epidemic is through vaccination. The goal of vaccination is to initiate a strong immune response that leads to the development of lasting and protective immunity against the targeted pathogen. The components of the immune system can be broadly classified into two categories: innate (nonspecific) and adaptive (specific) immune systems. (117,118) The innate immune system comprises natural killer (NK) cells, DCs, macrophages, monocytes, and innate lymphoid cells. NK cells eliminate infected cells; macrophages secrete cytokines and chemokines that induce inflammation for local defense or to facilitate tissue repair; DCs act as sentinels, carrying pathogens to adaptive immune cells; monocytes replenish macrophages and DCs; and innate lymphoid cells integrate and amplify cytokines. The adaptive immune system comprises antibodies, B cells, antigen-presenting cells (APCs), T cells, and T-helper (Th) cells. Antibodies are immunoglobins (Igs: IgA, IgD, IgE, IgE, IgG, and IgM), which are the first line of defense, secreted by B cells residing in lymph nodes, after recognition of an antigen, while T-helper (Th) cells assist Ig class switching. IgG and IgA are the two major types of antibodies secreted for direct neutralization of pathogens. The most important T cells are CD4+ and CD8+ T cells, which are the central coordinators of the immune response. CD4+ T cells recognize antigen peptides presented on APCs, while activated CD8+ T cells induce the death of infected cells. Activated CD4+ T cells, called Th1 cells, also produce IFN-γ, which drives the presentation pathway, facilitating recognition, generation of antiviral antibodies by B cells, and killing and disposal of infected cells with the help of NK cells and macrophages. Th cells and macrophages also produce interleukins (ILs) and tumor necrosis factor-α (TNF-α), two important classes of cytokines for antiviral immune responses. (119,120)Table 3 lists the NPs that can be used to trigger innate and adaptive immune responses against coronavirus infections. The most common NP-based vaccines are virus-like particles (VLPs) comprised of viral proteins, while NPs have also been used as vehicles for targeted RNA delivery to components of the innate immune system. The various NP-based vaccine designs are discussed in detail in the following sections.
Table 3. Nanoparticles as Immunogenic Agents for Vaccines
| NPs | conjugate/adjuvant | size (nm) | virus | level of study | approach and result | key takeaways for COVID-19 | ref |
|---|---|---|---|---|---|---|---|
| AuNPs | SARS-CoV S protein | 40, 100 | SARS | in vivo; BALB/c mice | induce strong IgG response | viral proteins form corona around AuNPs | (121) |
| VLPs with AuNPs | avian IBV S protein | AuNPs: 100 VLPs: 139 | IBV | in vivo; BALB/c mice | VLPs with AuNPs induce strong antigen-specific cellular immunity, IgG, IgA responses and reduced symptoms | VLPs with AuNPs retain 200–250 spike proteins for 7 days. virus-like zeta potential, lymphatic antigen delivery 6-fold better with AuNPs | (122) |
| VLPs from MERS-CoV S protein (full) | alum, Matrix M1 | - | MERS | in vivo; BALB/c mice | VLPs with Matrix M1 adjuvant induce high anti-S titers | completely blocks MERS-CoV replication in lungs | (123) |
| VLPs from SARS-CoV& MERS-CoVSprotein (full) | alum, Matrix M1 | ∼25 | SARS, MERS | in vivo; BALB/c mice | high antibody titers against homologous virus. virus-specific vaccine | Matrix M1 a powerful adjuvant, better than alum | (9) |
| VLPs from MERS-CoVSprotein | Ad5/MERS, alum | VLPs: 35; with alum: 80 | MERS | in vivo; BALB/c mice | CD8+ T cell response; TNF-a, IL-2, GM-CSF, and IFN-c responses; higher with Ad5/MERS | balanced Th1/Th2 activation generates a longer-lasting antibody response | (11) |
| VLPs from proteins and HRC subunit of SARS-CoVSprotein | 25–30 | SARS | in vivo; BALB/c mice | nanometer size and epitope display generate neutralizing mice antisera | conformation-specific and repetitive display of epitopes fully protect mice, even in absence of any adjuvant | (124) | |
| VLPs from bacteriophage P22 | IAV HAs | ∼26 | SARS, Influenza A | in vivo; C57BL/6 mice | intratracheal. recognizable by TLR-2 receptor. protect from infection and weight loss | repetitive HA epitope acts as self-adjuvant, formation of iBALT, protect mice from lethal doses of SARS-CoV | (8) |
| VLPs using canine parvovirus | MERS-CoV RBD, poly(I:C) | ∼25 | MERS | in vivo; BALB/c mice | mixed Th1 and Th2 responses. 1:320 increase in antibody titers | parvovirus-like VLPs do not cause disease in humans, safe platform, significant enhancement with poly(I:C) adjuvant | (125) |
| chitosan NPs | SARS-CoV N protein | 210 ± 60 | SARS | in vivo; BALB/c mice | intranasal, intramuscular. dendritic cell targeting. strong CD4+ response. high levels of IgG, IgG1, IgG2a, IgG2b, IgA, IFN-γ | cationic chitosan easily bind to DNA, better delivery than naked DNA, N protein better for broad-spectrum vaccines, mucosal pathway mimic infection route and DC targeted delivery, induce stronger antibody response | (93) |
| heat shock protein cage NPs | 120 | SARS, H1N1, RSV | in vivo; C57BL/6, BALB/c, μMT, C3H/HeJ, B6.SJL-Ptprca, Pep3b/BoyAiTac mice | mucosal delivery, induce strong nasal antibodies. formation of iBALT structures of B cells, CD4+ T cells, dendritic cells, and CD8+ T cells. minimal weight loss | broad-spectrum respiratory vaccine, fully protect mice against lethal doses. iBALT structures cause no inflammatory damage to lungs | (126) | |
| PLGA | STING, MERS-CoV S protein, MF59 | ∼148 | MERS | in vivo; C57BL/6 mice | STING encapsulated in PLGA induce strong RBD-specific CD4+, CD8+, balanced Th1/Th2 response. IgG2a; IFN-β, TNF-α, IL6 generation | polymer NPs for antigen + adjuvant delivery and cellular release, preferentially target lymphatic system | (127) |
| CDs | 1.6 | PEDV | in vitro; Vero & PK-15 cells | induce IFNs and proinflammatory cytokines | CDs can trigger innate immune responses | (76) |
a
Abbreviations: GM-CSF: granulocyte–macrophage colony-stimulating factor, HA: hemagglutinin, iBALT: inducible bronchus-associated lymphoid tissue, PLGA: poly(lactic-co-glycolic acid), STING: stimulator of interferon genes.
4.1. Virus-Like Particles
The goal of vaccination is to deliver antigens that activate the immune system against the virus. There are various ways to generate effective vaccines. Currently, most vaccines are based on whole viruses, either live attenuated viruses or inactivated viruses. (128) However, live vaccines are unstable and difficult to deliver, and the potential for genetic reversion to a more virulent form is always a concern. On the other hand, inactivated vaccines induce a weaker immune response. In both cases, ensuring complete inactivation, the absence of any further infection, and full compliance with safety standards takes 12–18 months. This timeline is far from ideal when fighting extremely virulent diseases such as COVID-19. The alternative is to design subunit vaccines that can prime immune responses via delivery of a subset of the viral proteins. Since these vaccines have no potential for replication, subunit vaccines offer a much safer approach and can often be approved faster. Such vaccines can be enabled by using VLPs, which are protein-based NPs containing viral envelope proteins without the accompanying genetic material. Due to their particulate nature, VLPs can mimic whole viruses and are much more stable than soluble antigens. Several VLP vaccines have been licensed for clinical use against various pathogens, such as hepatitis B virus (HBV), HPV, Norwalk virus, HSV, and malaria. Early VLP designs possessed limited immunogenicity due to the absence of S epitopes on the surface of the VLPs. (129) Incorporating S epitopes in later designs yielded more immunogenic VLPs.
Coleman et al. recently developed MERS-CoV spike (S) protein NPs that can protect mice from MERS-CoV infection. (123) The spike (S) protein, primarily responsible for receptor binding and cell entry, also induces neutralizing antibodies, making the S protein an ideal target for the anti-MERS vaccine. This vaccine also stops MERS-CoV replication in the lungs. In a related study, the same research group used full-length MERS-CoV and SARS-CoV S proteins to generate ∼25 nm diameter VLPs consisting of multiple S protein molecules. (9) Inoculation with these VLPs leads to the generation of neutralizing antibodies in mice. In both of these studies, neutralizing antibody levels were significantly boosted when the VLPs were used with alum and Matrix M1 adjuvants (15-fold with alum and 68-fold with Matrix M1), as seen in Figure 11a. (9,123) Alum is an aluminum salt that acts as a mild irritant, stimulating inflammasome responses, while Matrix M1 is a saponin-based adjuvant manufactured by Novavax, AB. (9) Novavax is currently developing COVID-19 vaccines using VLPs with full-length glycoproteins adjuvanted with Matrix M1. (118,123,130) Jung et al. also used MERS-CoV spike protein NPs with alum to induce specific IgG antibodies in mice. (11) The spike protein NPs had a diameter of 35 nm, which increased to 80 nm when the NPs were formulated with alum. When used in conjunction with a recombinant adenovirus serotype 5 encoding the MERS-CoV spike gene (Ad5/MERS), Th1/Th2 activation was balanced, generating a longer-lasting antibody response. Figure 11b shows the effectivity of this VLP in MERS-infected mice. The self-assembly of MERS-CoV protein NPs can be further assisted by a ferritin template to ensure the display of target antigens on the surface. (131) Since the spike S protein of coronaviruses is the most important antigenic determinant for inducing neutralizing antibodies, repetitive display of these S protein epitopes on the surface of the VLPs stimulates a stronger immune response. Pimental et al. observed that even using a smaller segment of the S protein may be sufficient if the epitopes are concentrated on the surface. (124) Using template-based synthesis with coiled-coil proteins, the C-terminal heptad repeat region (HRC), and a small segment of the S protein, they generated VLPs (see Figure 11c) that were able to stimulate anti-SARS antibodies even in the absence of an adjuvant, attributed largely to its nanometer size, repetitive display of the epitope, and good mimicry of the epitope’s natural configuration. Similar results were also observed by Sharma et al. when they incorporated multiple copies of the HA protein on the surface of the VLPs; HA is a surface-exposed glycoprotein and is the most highly immunogenic target for IAV. Immunization of IAV-infected mice with HA-conjugated surface VLPs provided full protection from morbidity and mortality without the need for additional adjuvants. (8) Thus, we observed that VLPs based on the spike S protein of MERS-CoV and SARS-CoV were effective in stimulating a strong antibody response. The antibody response is enhanced in the presence of adjuvants or by concentrating multiple repeating units of the S protein on the surface of the VLPs.
Figure 11
Figure 11. (a) Neutralization titers of coronavirus-spike-vaccinated mice. Serum from mice vaccinated with the indicated mix of spike protein and adjuvant was analyzed for neutralization capability and geometric mean titer (GMT), as graphed for all groups (10 mice per group). Stars denote statistically significant differences (p < 0.05). Reproduced with permission from ref (9). Copyright 2014 Elsevier. (b) Titers of neutralizing serum antibody against MERS-CoV in immunized mice. The rate of virus reduction for each group was calculated by comparison with the number of plaques in the control group (with PBS). The red dotted line indicates a 50% reduction in the virus. The mean reduction ± standard deviation values are shown. Reproduced with permission from ref (11). Copyright 2018 Elsevier. (c) Synthetic scheme and computer models for the formation of coiled-coil template-based complete peptide nanoparticles using the HRC region of the S epitope. The inset shows the various segments of the SARS-CoV S protein. Reproduced with permission from ref (124). Copyright 2009 Wiley.
Wang et al. designed novel chimeric VLPs using a canine parvovirus structural protein with the receptor-binding domain (RBD) of MERS-CoV. (125) Parvovirus-like particles are very stable, highly immunogenic, and do not cause disease in humans, making them a safe expression platform, while the RBD unit of MERS-CoV is a major antigenic determinant for antibody induction. RBD-specific humoral antibody responses were detected in mice treated with these VLPs 2 weeks after injection and were significantly enhanced in the presence of a polyriboinosinic acid [poly(I:C)] adjuvant. The VLPs produced a Th1-based response with significant IL-2 secretion, while the VLPs with poly(I:C) adjuvant produced mixed Th1 and Th2 responses, producing IFN-γ, IL-2, and IL-4 responses. The IgG antibody titer in mice treated with VLPs along with the adjuvant showed a 320-fold increase in mouse sera. The poly(I:C) adjuvant is able to activate a relatively high number of DCs in lymph nodes to generate a robust immune response. Cross-virus VLP design was also studied by Carter et al. (132) SARS-CoV polyprotein 1a (pp1a) self-assembled into VLPs that were found to be effective against idiopathic pulmonary fibrosis (IPF) caused by Herpesvirus saimiri (HVS). These two studies show that VLPs developed using subunits from one virus can serve as effective vaccines against other viruses as well. ARTES Biotechnology has utilized duck hepatitis B small surface antigen to design an enveloped VLP (eVLP) technology called METAVAX to deliver SARS-CoV-2 spike S protein-loaded vaccines. ARTES Biotechnology is also utilizing another vaccine technology using capsid VLPs (cVLPs), called SplitCore, to develop vaccines using SARS-CoV-2 S antigens. Ufovax, a spin-off vaccine company from Scripps Research, is also developing COVID-19 vaccines using self-assembling protein VLPs (1c-SApNP technology). Similar COVID-19 vaccines with VLPs are also being developed by Medicago (plant-derived VLPs), iBio, Inc. (SARS-CoV-2 VLPs), ExpreS2ion (protein subunit VLPs), GeoVax Laboratories (GV-MVA-VLP), BIKEN (protein subunit VLPs), Saiba GmbH (RBD-based VLPs), Imophoron Ltd. (ADDomer), LakePharma (protein subunit NPs), and VBI Vaccine Inc. (enveloped VLPs); most of these vaccines are already in either in the preclinical or clinical trial phase. (130)
4.2. Chitosan, Protein Cage, and Polymer Nanoparticles for Targeted Vaccine Delivery
NPs have been widely explored for drug delivery applications due to their favorable size, photothermal and magnetic properties, controlled release, and easy functionalization, enabling targeted attachment to specific cell types. (133−137) Many researchers have also attempted to utilize these attributes for targeted vaccine delivery to cellular components of the immune system. DCs are special sentinel cells, a type of APCs. Various strategies employed for selective targeting of DCs have shown great potential in the design of low-dose vaccines. (138) Raghuwanshi et al. designed a vaccine targeting DCs using chitosan NPs as delivery vehicles. (93) Chitosan is a natural polysaccharide that binds strongly to nucleic acids due to its cationic charge, (139,140) which makes these NPs ideal nucleic acid delivery vehicles, further aided by their excellent biocompatible, biodegradable, and nontoxic nature. Raghuwanshi et al. formulated NPs by loading negatively charged plasmid DNA encoding nucleocapsid (N) protein as a SARS-CoV vaccine antigen on cationic biotinylated chitosan NPs. Compared to the S protein, the N protein is more highly conserved in coronaviruses, which offers the ability to design broad-spectrum effectiveness across various mutating strands of the Coronaviridae family. For example, compared to the S gene in SARS-CoV-2, which is divergent (>25%) when compared to all other previously described SARS-related coronaviruses, the other three structural proteins are more highly conserved than the spike protein and are necessary for general coronavirus function. (12)
Additionally, similar to SARS-CoV and MERS-CoV, SARS-CoV-2 also primarily attacks the respiratory system, causing acute respiratory distress and pulmonary damage. (10,12,141,142) For this reason, Raghuwanshi et al. specifically administered the N protein-loaded chitosan NP vaccine intranasally, targeting the mucosal pathway, mimicking the route of an actual viral infection, (93) which induces both humoral and cellular immune responses. Naked DNA is ineffective in crossing mucosal barriers and is rapidly degraded by nucleases, while chitosan NPs transiently open the tight junctions to allow increased transport across the nasal mucosa. As a result, significant N protein-specific IgG, IgG1, IgG2a, and IgG2b antibodies, as well as IFN-γ and Th1 cytokine responses, were stimulated. Compared to systemic vaccination, mucosal vaccination is often more effective against mucosal pathogens due to the ability of these pathogens to induce secretory nasal antibodies. (93,126) Wiley et al. designed a safe broad-spectrum vaccine against multiple coronaviruses using a protein cage NP (PCN) that targets mucosal cells. (126) The PCN does not contain any antigen-specific proteins but is derived from a small heat shock protein (sHsp 16.5) instead, which causes the formation of inducible bronchus-associated lymphoid tissue (iBALT). The iBALT strategy provides an alternative approach for broad-spectrum viral protection in the lungs. The PCN-induced iBALT structures contain B cells, CD4+ T cells, DCs, and CD8+ T cells. CD4+ and CD8+ T cells accumulated rapidly in the lungs of PCN-treated mice. These iBALT responses protected the mice from lethal doses of various respiratory viruses (H1N1, SARS, RSV). Protection against SARS-CoV was already apparent within 3 days after infection, implying that innate mechanisms are also modulated by this PCN treatment (see Figure 12b). Despite the strong antiviral response, no histological damage was observed in the alveolar architecture of the lungs, and eosinophilic influx into the lungs was reduced. Thus, this PCN vaccination targeting iBALT microstructures can nonspecifically enhance immune protection against a diversity of respiratory viruses and in the absence of pulmonary inflammation, thus effectively protecting the host (see Figure 12c).
Figure 12
Figure 12. (a) Schematic illustration of dendritic cells targeting chitosan nanoparticles loaded with N proteins. Reproduced with permission from ref (93). Copyright 2012 American Chemical Society. (b) Survival of iBALT-induced PCN- and PBS-treated mice following challenge with SARS-coronavirus. All PCN-treated mice (■) survived infection with SARS-CoV, whereas all of the PBS-treated control mice (Δ) were dead by day 4 postinfection. (c) PCN-treated mice (■) maintained their bodyweight following SARS-CoV infection, whereas PBS-treated control mice (Δ) lost significant amounts of body weight shortly after infection. Reproduced with permission from ref (126). Copyright 2009 Wiley et al.
For cell-specific targeted vaccination strategies, NPs with dimensions of ∼100 nm have been generally found to be good for cellular uptake by DCs via phagocytosis, since they resemble the natural targets for DCs, such as viruses or bacteria. (118) Several studies have found that the submicron size is optimal for mucosal cell uptake and that NPs less than 200 nm in size are more readily transported by draining lymph nodes. (140) NPs with sizes of 20–200 nm have long circulation times and become enriched in lymph nodes, leading to enhanced lymphatic transport, allowing direct access to lymphoid-node-resistant DCs. (118) This feature enhances antigen uptake and presentation to B cells, enhancing the humoral response, or to T cells, allowing immunomodulation. (118) Cationic NPs have been widely used to deliver small interfering RNA (siRNA) to the lungs for the treatment of various respiratory diseases over the years via intranasal and intratracheal routes. (143) To combat a rapidly spreading virus such as SARS-CoV-2, mRNA (mRNA)-based vaccines are promising candidates, since they can be scaled rapidly. Cationic lipid NPs encapsulating mRNA are being widely explored for the development of COVID-19 vaccines. (144) Lipid NPs (LNPs) can deliver mRNA to the cytoplasm, where the mRNA can undergo direct translation to the target protein; this process can then trigger APCs and activation of B cells and T cells. (144) A vaccine developed by Moderna in collaboration with NIAID, containing mRNA encapsulated inside lipid NPs, is currently in phase-2 human clinical trials. (130,145) Moderna’s previous MERS and SARS vaccines developed using a similar design had demonstrated 90% reduction in viral load. (145) In addition, vaccines by BioNTech/Pfizer/Fosun Pharma (LNP–mRNA) are also in phase-1/2 trials, while Translate Bio/Sanofi Pasteur (LNP–mRNA), CanSino Biologics/Precision NanoSystems (LNP–mRNA), Daiichi-Sankyo (LNP–mRNA), BioPharma (mRNA VLPs), and RNACure Biopharma (LNP-encapsulated mRNA VLPs) are also developing lipid NP-encapsulated mRNA vaccines, currently in preclinical trials. (130)
Another type of NP used to deliver genetic materials to the lungs via nasal instillation is calcium phosphate (CaP). (146) Since CaP is a naturally occurring substance in mammalian hard tissues, it is a safe and biocompatible biomedical carrier. Additionally, acting as a mucosal adjuvant, CaP can initiate an immune response stronger than that induced by aluminum salts and for longer durations. (129) CaP is often encapsulated with polymers such as poly(lactic-coglycolic acid) (PLGA) and polyethylenimine (PEI), to increase cellular uptake. (146) PEI is known for facilitating targeted delivery and stimulating immune responses in alveolar cells and macrophages, along with other polymeric derivatives of PLGA, such as poly(dl-lactide-coglycolide) (PLG) and polylactide (PLA). (129,146) Due to their biocompatibility and excellent safety profile, PLGA and PLA have already been approved by the FDA to be used in various drug delivery systems for humans. (80,140) Using a thin (sub-20 nm) shell of PLGA with a large aqueous core, Lin et al. made a hollow NP to entrap a soluble stimulator of IFN genes (STING) adjuvant (see Figure 13). (127) Due to the acid-sensitive PLGA hydrolysis, the NPs readily release the adjuvant upon cellular uptake, as seen in Figure 13. Localized at the endoplasmic reticulum, STING is a potent inducer of proinflammatory cytokines such as IFN-β, TNF-α, and IL-6. When combined with the MERS-CoV spike protein, the STING-PLGA NP size increases to ∼148 nm, which leads to a virus-like distribution of the NPs, synchronizing lymph node delivery of surface-coated antigens and interiorly loaded adjuvant. Further conjugation with the state-of-the-art influenza adjuvant MF59 (Addavax) induced significantly higher levels of antigen-specific antibodies due to balanced Th1 and Th2 responses. Higher antibody titers and longer-lasting responses due to a balanced Th1/Th2 response were also observed by Jung et al., as described previosuly. (11) The polymer-based NPs with STING and MF59 adjuvants were superior in their ability to mount humoral responses compared to free STING agonists or MF59 alone. This study strongly demonstrated the advantages of hollow polymeric NPs as vaccine delivery vehicles due to their biocompatibility, size consistency, colloidal stability, tunable adjuvant loading, pH-responsive release, and antigen functionalizability.
Figure 13
Figure 13. Characterization of adjuvant-loaded viromimetic nanoparticles. (a) Schematic showing the preparation of the viromimetic nanoparticle vaccine. Hollow PLGA nanoparticles with encapsulated adjuvant and surface maleimide linkers were prepared using a double-emulsion technique. Recombinant viral antigens were then conjugated to the surface of nanoparticles via a thiol–maleimide linkage. (b) Cryo-electron microscopy of cdGMP-loaded hollow nanoparticles. (c) Size distribution of nanoparticles determined by dynamic light scattering (DLS). (d) In vitro release profiles of cdGMP from PLGA hollow nanoparticles at pH 5 and 7. Reproduced with permission from ref (127). Copyright 2019 WILEY-VCH Verlag GmbH & Co., KGaA, Weinheim.
4.3. Quantum Dots and Gold Nanoparticles
QDs, with sizes much smaller than the aforementioned NPs, have also been utilized for designing vaccines against coronaviruses. Positively charged carbon QDs with dimensions of ∼1.6 nm, made from curcumin, were studied as vaccines against PEDV, a model coronavirus. (76) Although these CDs primarily blocked viral cell entry, they also induced the production of ISGs that suppress viral replication and budding. Ag2S nanocrystals (NCs), another type of QD, were also found to positively regulate ISGs and the expression of proinflammatory cytokines. (74) However, among inorganic NPs, the most commonly employed NPs in vaccine design are AuNPs. Sekimukai et al. discovered that AuNPs can act as both an antigen carrier for the SARS-CoV spike S protein and an adjuvant. (121) AuNPs bind to the S protein via electrostatic interactions, forming a protein corona around the AuNPs. Mice immunized with these NPs showed Th1 and Th2 responses; however, these responses were accompanied by allergic inflammation and eosinophilic infiltration. Chen et al. utilized AuNPs to formulate synthetic VLPs (sVLPs) by incubating 100 nm AuNPs in a solution containing the spike S protein of avian coronavirus infectious bronchitis virus (IBV), as shown in Figure 14. (122) Following removal of free protein, antigen-loaded AuNPs were recovered that resembled natural viral proteins, as seen in Figure 14. Protein corona formation increased the NP size to 139 nm, which remained stable over a 7 day period, with each particle retaining approximately 200–250 spike proteins. Compared to inoculation with free proteins, vaccination with these synthetic VLPs showed enhanced lymphatic antigen delivery (6-fold), stronger antibody titers, increased T cell response, and reduced symptoms (see Figure 14). Thus, there are multiple advantages to using AuNPs as next-generation vaccine delivery agents. (1) Inorganic NPs such as AuNPs have high surface energy, leading to spontaneous protein corona formation. (121) As a result, a smaller amount of antigen is required than VLPs to make antigen-exposing NPs of sizes comparable to those of coronaviruses, generating CD4+ T cell and B cell responses. (147) Easy functionalization of AuNPs allows the loading of various other nucleic acids as well. (2) With the NP acting as an adjuvant itself, additional adjuvants are not necessary. (121,147) (3) AuNPs used as antigen carriers also stimulate phagocytic activity of lymphoid cells, stimulate APCs, and induce the release of inflammatory mediators. (147) Localization of AuNPs to lymphatic tissues and cells is notable, as it mimics what occurs during a natural infection. AuNPs primarily enter cells via phagocytosis, stimulating macrophages, DCs, and lymphocytes. (147) Phagocytosis of NPs is determined by their size and shape. (147) AuNPs with dimensions of 40–100 nm are ideal for phagocytosis, while shape dependence follows the order ellipsoid > spheres > rods > cubes, although in some cases, rods are internalized better than spheres. (118,148,149) However, larger spherical virus-like AuNPs generate the strongest antibody responses. (4) AuNPs have good stability and low cytotoxicity. (88,148)
Figure 14
Figure 14. (a) Schematic depiction of the preparation of avian coronavirus sVLPs. sVLPs are prepared in optimized mixtures containing viral proteins and 100 nm gold nanoparticles via spontaneous protein corona formation. (b) Transmission electron microscopy of sVLPs (left) and native IBV virions (right) following immunogold staining against IBV spike proteins. Scale bars = 50 nm. (c) Size and zeta potential of AuNPs, sVLPs, and native IBV virions as analyzed by nanoparticle tracking analysis. Bars represent the mean ± s.d. (n = 3). (d) Vaccination, tissue sample collection, and virus challenge schedule in an avian model of coronavirus infection. (e) Virus-specific serum IgG titers observed in animals vaccinated with free proteins, a commercial whole inactivated virus (WIV) vaccine, and sVLPs. Lines and boxes represent the upper extreme; 25th, 50th, and 75th percentiles; and lower extreme (n = 6). (f) Virus-specific serum IgA titers in animals vaccinated with the different formulations. Lines and boxes represent the upper extreme; 25th, 50th, and 75th percentiles; and lower extreme (n = 6). Reproduced with permission from ref (122). Copyright 2016 Elsevier.
5. Summary and Perspectives
ARTICLE SECTIONS
5.1. Nanoparticles for Diagnostics
NPs have been applied to various kinds of virus detection methods. Metal NPs and QDs with unique optical properties have the advantages of enhanced sensitivity for optical biosensing. Meanwhile, MNPs are mainly applied to the virus extraction process due to their magnetic properties. Additionally, the nanohybrid structures combine the advantages of each type of NP to improve the efficiency of virus detection. Recently, NP-based virus detection has been reported as a promising technique to detect the recently discovered SARS-CoV-2, the virus that causes COVID-19. With further research and development, NPs will undoubtedly play an important role in improving not only coronavirus detection efficiency but also other biological pathogen diagnoses.
5.2. Nanoparticles for Therapeutics
Overall, the studies covered in this section show that various NPs can be used to design drugs aimed at disrupting the attachment of SARS-CoV-2 to the ACE2 receptor and blocking the cell entry process while themselves remaining largely nontoxic toward the host cells. Effective antiviral therapies, especially in the early stage of infection, are vitally important to halt viral proliferation long enough for the immune system to respond to the virus and limit cellular damage inflicted by viral invasion as well as to minimize genetic mutations caused by the high replication frequency of the virus, which might lead to therapeutic resistance. NPs with various structures, compositions, and conjugations have been fabricated and evaluated in multiple conditions as highly effective enhancements or alternatives to many existing antiviral therapeutics associated with increasing drug resistance. The antiviral performance, stability, and biocompatibility of these NPs have been rigorously investigated on different human-infecting viruses ranging from members of the coronavirus family to other viruses with close structural similarity to SARS-CoV-2 itself. Using novel antiviral approaches with flexible combinations, many NPs have also been demonstrated to be effective against a broad spectrum of viruses with minimal cytotoxicity, suggesting that these NPs are good research candidates for NP-based antiviral therapies to fight the COVID-19 pandemic.
5.3. Nanoparticles as Immunogenic Agents for Vaccines
Overall, the studies covered in this section offer valuable insight needed for the development of vaccines for COVID-19. The following four conclusions can be drawn: (1) Self-assembled VLPs, template-based and supported VLPs, and synthetic VLPs can all be systematically formulated in sizes and shapes that mimic those of original coronaviruses. These features help induce strong immune responses while avoiding exposure to the virulent genetic components of the virus itself. (2) Repetitive decoration of antigens on the surface of NP vaccines can enhance immune responses, even when using smaller subsets of the proteins; this effect can be further enhanced by matching the natural configuration of the epitopes. Vaccine development has typically exploited coronavirus S protein epitopes, but N protein epitopes can also be utilized to design broad-spectrum vaccines. (3) NPs offer the opportunity to combine antigen delivery abilities with adjuvant properties. (4) Vaccines targeted specifically toward mucosal cells, DCs, and lymph nodes generate stronger localized immune responses against respiratory viruses such as SARS-CoV-2. Nanosized particles (40–200 nm) are especially suitable for targeted delivery to mucosal and alveolar structures, mimicking natural infection routes and inducing direct immune responses in the worst affected tissues.
Thus, NPs are expected to play a major role in the fight against COVID-19. The optical and magnetic properties of various NPs can be utilized for building diagnostic test kits. The stark morphological and physicochemical similarities of SARS-CoV-2 with synthetic NPs also make NPs a powerful tool for intervention. NPs can be systematically functionalized with various proteins, polymers, and functional groups to perform specific inhibitory functions while also acting as excellent delivery vehicles. NPs offer possibilities for fast and safe vaccine development using subunit proteins instead of whole viruses. Additionally, NPs can also be utilized to make broad-spectrum respiratory drugs and vaccines that can protect us from seasonal viruses and prepare us for future pandemics as well.
Author Information
ARTICLE SECTIONS
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T. Randall Lee - Department of Chemistry and the Texas Center for Superconductivity, University of Houston, 4800 Calhoun Road, Houston, Texas 77204-5003, United States;
http://orcid.org/0000-0001-9584-8861;
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Riddhiman Medhi - Department of Chemistry and the Texas Center for Superconductivity, University of Houston, 4800 Calhoun Road, Houston, Texas 77204-5003, United States;http://orcid.org/0000-0002-2368-2468
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Pannaree Srinoi - Department of Chemistry and the Texas Center for Superconductivity, University of Houston, 4800 Calhoun Road, Houston, Texas 77204-5003, United States;http://orcid.org/0000-0003-4400-468X
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Nhat Ngo - Department of Chemistry and the Texas Center for Superconductivity, University of Houston, 4800 Calhoun Road, Houston, Texas 77204-5003, United States;http://orcid.org/0000-0001-5710-1601
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Hung-Vu Tran - Department of Chemistry and the Texas Center for Superconductivity, University of Houston, 4800 Calhoun Road, Houston, Texas 77204-5003, United States;http://orcid.org/0000-0001-8536-2737
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Acknowledgments
ARTICLE SECTIONS
We thank the Air Force Office of Scientific Research (AFOSR FA9550-18-1-0094), the Robert A. Welch Foundation (E-1320), the Texas Center for Superconductivity, and the University of Houston Advanced Manufacturing Institute for generously supporting this research.
References
ARTICLE SECTIONS
This article references 149 other publications.
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1Chan, J. F. -W.; Yuan, S.; Kok, K.-H.; To, K. K. -W.; Chu, H.; Yang, J.; Xing, F.; Liu, J.; Yip, C. C. -Y.; Poon, R. W. -S.; Tsoi, H.-W.; Lo, S. K. -F.; Chan, K.-H.; Poon, V. K. -M.; Chan, W.-M.; Ip, J. D.; Cai, J.-P.; Cheng, V. C. -C.; Chen, H.; Hui, C. K. -M.; Yuen, K.-Y. A Familial Cluster of Pneumonia Associated with the 2019 Novel Coronavirus Indicating Person-to-Person Transmission: A Study of a Family Cluster. Lancet 2020, 395, 514– 523, DOI: 10.1016/S0140-6736(20)30154-9Google Scholar1https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhs1Ojsro%253D&md5=a00abba6fd95be357f1b4a0152da93c0A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family clusterChan, Jasper Fuk-Woo; Yuan, Shuofeng; Kok, Kin-Hang; To, Kelvin Kai-Wang; Chu, Hin; Yang, Jin; Xing, Fanfan; Liu, Jieling; Yip, Cyril Chik-Yan; Poon, Rosana Wing-Shan; Tsoi, Hoi-Wah; Lo, Simon Kam-Fai; Chan, Kwok-Hung; Poon, Vincent Kwok-Man; Chan, Wan-Mui; Ip, Jonathan Daniel; Cai, Jian-Piao; Cheng, Vincent Chi-Chung; Chen, Honglin; Hui, Christopher Kim-Ming; Yuen, Kwok-YungLancet (2020), 395 (10223), 514-523CODEN: LANCAO; ISSN:0140-6736. (Elsevier Ltd.)An ongoing outbreak of pneumonia assocd. with a novel coronavirus was reported in Wuhan city, Hubei province, China. Affected patients were geog. linked with a local wet market as a potential source. No data on person-to-person or nosocomial transmission have been published to date. In this study, we report the epidemiol., clin., lab., radiol., and microbiol. findings of five patients in a family cluster who presented with unexplained pneumonia after returning to Shenzhen, Guangdong province, China, after a visit to Wuhan, and an addnl. family member who did not travel to Wuhan. Phylogenetic anal. of genetic sequences from these patients were done. From Jan 10, 2020, we enrolled a family of six patients who travelled to Wuhan from Shenzhen between Dec 29, 2019 and Jan 4, 2020. Of six family members who travelled to Wuhan, five were identified as infected with the novel coronavirus. Addnl., one family member, who did not travel to Wuhan, became infected with the virus after several days of contact with four of the family members. None of the family members had contacts with Wuhan markets or animals, although two had visited a Wuhan hospital. Five family members (aged 36-66 years) presented with fever, upper or lower respiratory tract symptoms, or diarrhea, or a combination of these 3-6 days after exposure. They presented to our hospital (The University of Hong Kong-Shenzhen Hospital, Shenzhen) 6-10 days after symptom onset. They and one asymptomatic child (aged 10 years) had radiol. ground-glass lung opacities. Older patients (aged >60 years) had more systemic symptoms, extensive radiol. ground-glass lung changes, lymphopenia, thrombocytopenia, and increased C-reactive protein and lactate dehydrogenase levels. The nasopharyngeal or throat swabs of these six patients were neg. for known respiratory microbes by point-of-care multiplex RT-PCR, but five patients (four adults and the child) were RT-PCR pos. for genes encoding the internal RNA-dependent RNA polymerase and surface Spike protein of this novel coronavirus, which were confirmed by Sanger sequencing. Phylogenetic anal. of these five patients' RT-PCR amplicons and two full genomes by next-generation sequencing showed that this is a novel coronavirus, which is closest to the bat severe acute respiratory syndrome (SARS)-related coronaviruses found in Chinese horseshoe bats. Our findings are consistent with person-to-person transmission of this novel coronavirus in hospital and family settings, and the reports of infected travelers in other geog. regions. The Shaw Foundation Hong Kong, Michael Seak-Kan Tong, Respiratory Viral Research Foundation Limited, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund Limited, Marina Man-Wai Lee, the Hong Kong Hainan Com. Assocn. South China Microbiol. Research Fund, Sanming Project of Medicine (Shenzhen), and High Level-Hospital Program (Guangdong Health Commission).
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2Huang, C.; Wang, Y.; Li, X.; Ren, L.; Zhao, J.; Hu, Y.; Zhang, L.; Fan, G.; Xu, J.; Gu, X.; Cheng, Z.; Yu, T.; Xia, J.; Wei, Y.; Wu, W.; Xie, X.; Yin, W.; Li, H.; Liu, M.; Xiao, Y.; Gao, H.; Guo, L.; Xie, J.; Wang, G.; Jiang, R.; Gao, Z.; Jin, Q.; Wang, J.; Cao, B. Clinical Features of Patients Infected with 2019 Novel Coronavirus in Wuhan, China. Lancet 2020, 395, 497– 506, DOI: 10.1016/S0140-6736(20)30183-5Google Scholar2https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhs1Kqu7c%253D&md5=b279b965c1054d99e60f673859c03b49Clinical features of patients infected with 2019 novel coronavirus in Wuhan, ChinaHuang, Chaolin; Wang, Yeming; Li, Xingwang; Ren, Lili; Zhao, Jianping; Hu, Yi; Zhang, Li; Fan, Guohui; Xu, Jiuyang; Gu, Xiaoying; Cheng, Zhenshun; Yu, Ting; Xia, Jiaan; Wei, Yuan; Wu, Wenjuan; Xie, Xuelei; Yin, Wen; Li, Hui; Liu, Min; Xiao, Yan; Gao, Hong; Guo, Li; Xie, Jungang; Wang, Guangfa; Jiang, Rongmeng; Gao, Zhancheng; Jin, Qi; Wang, Jianwei; Cao, BinLancet (2020), 395 (10223), 497-506CODEN: LANCAO; ISSN:0140-6736. (Elsevier Ltd.)A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiol., clin., lab., and radiol. characteristics and treatment and clin. outcomes of these patients. All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analyzed data on patients with lab.-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiol. and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. By Jan 2, 2020, 41 admitted hospital patients had been identified as having lab.-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0-58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum prodn. (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0-13·0]). 26 (63%) Of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was assocd. with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiol., duration of human transmission, and clin. spectrum of disease need fulfilment by future studies. Ministry of Science and Technol., Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technol. Commission.
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3Wrapp, D.; Wang, N.; Corbett, K. S.; Goldsmith, J. A.; Hsieh, C.-L.; Abiona, O.; Graham, B. S.; McLellan, J. S. Cryo-EM Structure of the 2019-Ncov Spike in the Prefusion Conformation. Science 2020, 367, 1260– 1263, DOI: 10.1126/science.abb2507Google Scholar3https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXkvFemt70%253D&md5=27d08cbb9a43d1da051a8a92a9f68aa5Cryo-EM structure of the 2019-nCoV spike in the prefusion conformationWrapp, Daniel; Wang, Nianshuang; Corbett, Kizzmekia S.; Goldsmith, Jory A.; Hsieh, Ching-Lin; Abiona, Olubukola; Graham, Barney S.; McLellan, Jason S.Science (Washington, DC, United States) (2020), 367 (6483), 1260-1263CODEN: SCIEAS; ISSN:1095-9203. (American Association for the Advancement of Science)The outbreak of a novel coronavirus (2019-nCoV) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure development, we detd. a 3.5-angstrom-resoln. cryo-electron microscopy structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also provide biophys. and structural evidence that the 2019-nCoV S protein binds angiotensin-converting enzyme 2 (ACE2) with higher affinity than does severe acute respiratory syndrome (SARS)-CoV S. Addnl., we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable the rapid development and evaluation of medical countermeasures to address the ongoing public health crisis.
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4Zhang, L.; Lin, D.; Sun, X.; Curth, U.; Drosten, C.; Sauerhering, L.; Becker, S.; Rox, K.; Hilgenfeld, R. Crystal Structure of SARS-CoV-2 Main Protease Provides a Basis for Design of Improved α-Ketoamide Inhibitors. Science 2020, 368, 409– 412, DOI: 10.1126/science.abb3405Google Scholar4https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXnslKrtL8%253D&md5=9ac417c20f54c3327f9de9088b512d52Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitorsZhang, Linlin; Lin, Daizong; Sun, Xinyuanyuan; Curth, Ute; Drosten, Christian; Sauerhering, Lucie; Becker, Stephan; Rox, Katharina; Hilgenfeld, RolfScience (Washington, DC, United States) (2020), 368 (6489), 409-412CODEN: SCIEAS; ISSN:1095-9203. (American Association for the Advancement of Science)The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is a global health emergency. An attractive drug target among coronaviruses is the main protease (Mpro, also called 3CLpro) because of its essential role in processing the polyproteins that are translated from the viral RNA. We report the x-ray structures of the unliganded SARS-CoV-2 Mpro and its complex with an α-ketoamide inhibitor. This was derived from a previously designed inhibitor but with the P3-P2 amide bond incorporated into a pyridone ring to enhance the half-life of the compd. in plasma. On the basis of the unliganded structure, we developed the lead compd. into a potent inhibitor of the SARS-CoV-2 Mpro. The pharmacokinetic characterization of the optimized inhibitor reveals a pronounced lung tropism and suitability for administration by the inhalative route.
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5Gandhi, M.; Yokoe, D. S.; Havlir, D. V. Asymptomatic Transmission, the Achilles’ Heel of Current Strategies to Control Covid-19. N. Engl. J. Med. 2020, 382, 2158– 2160, DOI: 10.1056/NEJMe2009758Google Scholar5https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtVGqsrfF&md5=9758bf5634365e6044e42b6c8b57b5b3Asymptomatic transmission, the Achilles' heel of current strategies to control Covid-19Gandhi, Monica; Yokoe, Deborah S.; Havlir, Diane V.New England Journal of Medicine (2020), 382 (22), 2158-2160CODEN: NEJMAG; ISSN:1533-4406. (Massachusetts Medical Society)A review. A brief editorial discussing the role of asymptomatic transmission in the spread and severity of the current SARS-CoV-2 pandemic. The authors contrast the differences between the current SARS-CoV-2 pandemic and the SARS-CoV-1 epidemic of 2003. High levels of SARS-CoV-2 virus are shed from the upper respiratory tract of patients, even before symptoms are obsd. In contrast, replication of SARS-CoV-1 occurs mainly in the lower respiratory tract, and viral shedding occurs later, when patients are symptomatic. Asymptomatic transmission of SARS-CoV-2 is the Achilles' heel of COVID-19 pandemic control through the public health strategies we have currently deployed. Because of this, testing of asymptomatic individuals, social distancing, and the general use of face masks in public spaces are the main tools to deal with this pandemic.
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6Rinaldi, A. Free, at Last! The Progress of New Disease Eradication Campaigns for Guinea Worm Disease and Polio, and the Prospect of Tackling Other Diseases. EMBO Rep. 2009, 10, 215– 221, DOI: 10.1038/embor.2009.19Google Scholar6https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXisVOrt7s%253D&md5=c058c35bdc62879001a85d7bf9b3fc35Free, at last! The progress of new disease eradication campaigns for Guinea worm disease and polio, and the prospect of tackling other diseasesRinaldi, AndreaEMBO Reports (2009), 10 (3), 215-221CODEN: ERMEAX; ISSN:1469-221X. (Nature Publishing Group)There is no expanded citation for this reference.
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7Sued, O.; Figueroa, M. I.; Cahn, P. Clinical Challenges in HIV/AIDS: Hints for Advancing Prevention and Patient Management Strategies. Adv. Drug Delivery Rev. 2016, 103, 5– 19, DOI: 10.1016/j.addr.2016.04.016Google Scholar7https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XntVOmsL4%253D&md5=1adcabc206ee3f3a698a674fd470a78bClinical challenges in HIV/AIDS: Hints for advancing prevention and patient management strategiesSued, Omar; Figueroa, Maria Ines; Cahn, PedroAdvanced Drug Delivery Reviews (2016), 103 (), 5-19CODEN: ADDREP; ISSN:0169-409X. (Elsevier B.V.)Acquired immune deficiency syndrome has been one of the most devastating epidemics of the last century. The current est. for people living with the HIV is 36.9 million. Today, despite availability of potent and safe drugs for effective treatment, lifelong therapy is required for preventing HIV re-emergence from a pool of latently infected cells. However, recent evidence show the importance to expand HIV testing, to offer antiretroviral treatment to all infected individuals, and to ensure retention through all the cascade of care. In addn., circumcision, pre-exposure prophylaxis, and other biomedical tools are now available for included in a comprehensive preventive package. Use of all the available tools might allow cutting the HIV transmission in 2030. In this article, we review the status of the epidemic, the latest advances in prevention and treatment, the concept of treatment as prevention and the challenges and opportunities for the HIV cure agenda.
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8Sharma, J.; Shepardson, K.; Johns, L. L.; Wellham, J.; Avera, J.; Schwarz, B.; Rynda-Apple, A.; Douglas, T. A Self-Adjuvanted, Modular, Antigenic VLP for Rapid Response to Influenza Virus Variability. ACS Appl. Mater. Interfaces 2020, 12, 18211– 18224, DOI: 10.1021/acsami.9b21776Google Scholar8https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXmt1erur8%253D&md5=1cc160e97a978a8dce1842636bc8ea17A Self-Adjuvanted, Modular, Antigenic VLP for Rapid Response to Influenza Virus VariabilitySharma, Jhanvi; Shepardson, Kelly; Johns, Laura L.; Wellham, Julia; Avera, John; Schwarz, Benjamin; Rynda-Apple, Agnieszka; Douglas, TrevorACS Applied Materials & Interfaces (2020), 12 (16), 18211-18224CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)The continuous evolution of influenza A virus (IAV) requires the influenza vaccine formulations to be updated annually to provide adequate protection. Recombinant protein-based vaccines provide safer, faster and a more scalable alternative to the conventional embryonated egg approach for developing vaccines. However, these vaccines are typically poorer in immunogenicity than the vaccines contg. inactivated or attenuated influenza viruses and require administration of a large antigen dosage together with potent adjuvants. Presentation of protein-antigens on the surface of virus-like particles (VLP) provides an attractive strategy to rapidly induce stronger antigen-specific immune responses. Here we have examd. the immunogenic potential and protective efficacy of P22 VLPs conjugated with multiple copies of the globular head domain of the hemagglutinin (HA) protein from the PR8 strain of IAV in a murine model of influenza pathogenesis. Using a covalent attachment strategy (SpyTag/SpyCatcher) we conjugated the HA globular head, which was recombinantly expressed in a genetically modified E. coli strain and found to refold as a monomer, to pre-assembled P22 VLPs. Immunization of mice with this P22-HAhead conjugate provided full protection from morbidity and mortality following infection with a homologous IAV strain. Moreover, the P22-HAhead conjugate also elicited an accelerated and enhanced HA head specific IgG response, which was significantly higher than the sol. HA head, or the admixt. of P22 and HA head without the need for adjuvants. Thus, our results show that the HA head can be easily prepd. by in vitro refolding in a modified E. coli strain, maintaining its intact structure, and enabling the induction of a strong immune response when conjugated to P22 VLPs, even when presented as a monomer. These results also demonstrate that the P22 VLPs can be rapidly modified in a modular fashion resulting in an effective vaccine construct that can generate protective immunity without the need for addnl. adjuvants.
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9Coleman, C. M.; Liu, Y. V.; Mu, H.; Taylor, J. K.; Massare, M.; Flyer, D. C.; Glenn, G. M.; Smith, G. E.; Frieman, M. B. Purified Coronavirus Spike Protein Nanoparticles Induce Coronavirus Neutralizing Antibodies in Mice. Vaccine 2014, 32, 3169– 3174, DOI: 10.1016/j.vaccine.2014.04.016Google Scholar9https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXnsVWltbc%253D&md5=ae9d0bdd54af7796725c5f7c4755e4c9Purified coronavirus spike protein nanoparticles induce coronavirus neutralizing antibodies in miceColeman, Christopher M.; Liu, Ye V.; Mu, Haiyan; Taylor, Justin K.; Massare, Michael; Flyer, David C.; Glenn, Gregory M.; Smith, Gale E.; Frieman, Matthew B.Vaccine (2014), 32 (26), 3169-3174CODEN: VACCDE; ISSN:0264-410X. (Elsevier Ltd.)Development of vaccination strategies for emerging pathogens are particularly challenging because of the sudden nature of their emergence and the long process needed for traditional vaccine development. Therefore, there is a need for development of a rapid method of vaccine development that can respond to emerging pathogens in a short time frame. The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in late 2012 demonstrate the importance of coronaviruses as emerging pathogens. The spike glycoproteins of coronaviruses reside on the surface of the virion and are responsible for virus entry. The spike glycoprotein is the major immunodominant antigen of coronaviruses and has proven to be an excellent target for vaccine designs that seek to block coronavirus entry and promote antibody targeting of infected cells. Vaccination strategies for coronaviruses have involved live attenuated virus, recombinant viruses, non-replicative virus-like particles expressing coronavirus proteins or DNA plasmids expressing coronavirus genes. None of these strategies has progressed to an approved human coronavirus vaccine in the ten years since SARS-CoV emerged. Here we describe a novel method for generating MERS-CoV and SARS-CoV full-length spike nanoparticles, which in combination with adjuvants are able to produce high titer antibodies in mice.
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10Schindewolf, C.; Menachery, V. D. Middle East Respiratory Syndrome Vaccine Candidates: Cautious Optimism. Viruses 2019, 11, 74, DOI: 10.3390/v11010074Google Scholar10https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtlOrtLnL&md5=117ad302d878297978c7e81605ce694aMiddle East respiratory syndrome vaccine candidates: cautious optimismSchindewolf, Craig; Menachery, Vineet D.Viruses (2019), 11 (1), 74CODEN: VIRUBR; ISSN:1999-4915. (MDPI AG)A review. Efforts towards developing a vaccine for Middle East respiratory syndrome coronavirus (MERS-CoV) have yielded promising results. Utilizing a variety of platforms, several vaccine approaches have shown efficacy in animal models and begun to enter clin. trials. In this review, we summarize the current progress towards a MERS-CoV vaccine and highlight potential roadblocks identified from previous attempts to generate coronavirus vaccines.
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11Jung, S.-Y.; Kang, K. W.; Lee, E.-Y.; Seo, D.-W.; Kim, H.-L.; Kim, H.; Kwon, T.; Park, H.-L.; Kim, H.; Lee, S.-M.; Nam, J.-H. Heterologous Prime–Boost Vaccination with Adenoviral Vector and Protein Nanoparticles Induces Both Th1 and Th2 Responses against Middle East Respiratory Syndrome Coronavirus. Vaccine 2018, 36, 3468– 3476, DOI: 10.1016/j.vaccine.2018.04.082Google Scholar11https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXptVCqtrk%253D&md5=10552fd92b8dd1c5d847219fc1edf27fHeterologous prime-boost vaccination with adenoviral vector and protein nanoparticles induces both Th1 and Th2 responses against Middle East respiratory syndrome coronavirusJung, Seo-Yeon; Kang, Kyung Won; Lee, Eun-Young; Seo, Dong-Won; Kim, Hong-Lim; Kim, Hak; Kwon, TaeWoo; Park, Hye-Lim; Kim, Hun; Lee, Sang-Myeong; Nam, Jae-HwanVaccine (2018), 36 (24), 3468-3476CODEN: VACCDE; ISSN:0264-410X. (Elsevier Ltd.)In this study, we developed two types of MERS-CoV vaccines: a recombinant adenovirus serotype 5 encoding the MERS-CoV spike gene (Ad5/MERS) and spike protein nanoparticles formulated with aluminum (alum) adjuvant. Next, we tested a heterologous prime-boost vaccine strategy, which compared priming with Ad5/MERS and boosting with spike protein nanoparticles and vice versa, with homologous prime-boost vaccination comprising priming and boosting with either spike protein nanoparticles or Ad5/MERS. Although both types of vaccine could induce specific IgG against MERS-CoV, neutralizing antibodies against MERS-CoV were induced only by heterologous prime-boost immunization and homologous immunization with spike protein nanoparticles. Heterologous prime-boost vaccination regimens including Ad5/MERS elicited simultaneous Th1 and Th2 responses, but homologous prime-boost regimens did not. Thus, heterologous prime-boost may induce longer-lasting immune responses against MERS-CoV because of an appropriate balance of Th1/Th2 responses. However, both heterologous prime-boost and homologous spike protein nanoparticles vaccinations could provide protection from MERS-CoV challenge in mice. Our results demonstrate that heterologous immunization by priming with Ad5/MERS and boosting with spike protein nanoparticles could be an efficient prophylactic strategy against MERS-CoV infection.
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12Udugama, B.; Kadhiresan, P.; Kozlowski, H. N.; Malekjahani, A.; Osborne, M.; Li, V. Y. C.; Chen, H.; Mubareka, S.; Gubbay, J. B.; Chan, W. C. W. Diagnosing Covid-19: The Disease and Tools for Detection. ACS Nano 2020, 14, 3822– 3835, DOI: 10.1021/acsnano.0c02624Google Scholar12https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXlvFChtrk%253D&md5=0e9ea61666e72862e7587ceb281c5fe4Diagnosing COVID-19: The Disease and Tools for DetectionUdugama, Buddhisha; Kadhiresan, Pranav; Kozlowski, Hannah N.; Malekjahani, Ayden; Osborne, Matthew; Li, Vanessa Y. C.; Chen, Hongmin; Mubareka, Samira; Gubbay, Jonathan B.; Chan, Warren C. W.ACS Nano (2020), 14 (4), 3822-3835CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)A review. COVID-19 has spread globally since its discovery in Hubei province, China in Dec. 2019. A combination of computed tomog. imaging, whole genome sequencing, and electron microscopy were initially used to screen and identify SARS-CoV-2, the viral etiol. of COVID-19. The aim of this review article is to inform the audience of diagnostic and surveillance technologies for SARS-CoV-2 and their performance characteristics. We describe point-of-care diagnostics that are on the horizon and encourage academics to advance their technologies beyond conception. Developing plug-and-play diagnostics to manage the SARS-CoV-2 outbreak would be useful in preventing future epidemics.
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13Yan, R.; Zhang, Y.; Li, Y.; Xia, L.; Guo, Y.; Zhou, Q. Structural Basis for the Recognition of SARS-CoV-2 by Full-Length Human ACE2. Science 2020, 367, 1444– 1448, DOI: 10.1126/science.abb2762Google Scholar13https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXlslymsLo%253D&md5=ff4dfdfc646ea878cfb325019160e94aStructural basis for the recognition of SARS-CoV-2 by full-length human ACE2Yan, Renhong; Zhang, Yuanyuan; Li, Yaning; Xia, Lu; Guo, Yingying; Zhou, QiangScience (Washington, DC, United States) (2020), 367 (6485), 1444-1448CODEN: SCIEAS; ISSN:1095-9203. (American Association for the Advancement of Science)Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for severe acute respiratory syndrome coronavirus (SARS-CoV) and the new coronavirus (SARS-CoV-2) that is causing the serious coronavirus disease 2019 (COVID-19) epidemic. Here, we present cryo-electron microscopy structures of full-length human ACE2 in the presence of the neutral amino acid transporter B0AT1 with or without the receptor binding domain (RBD) of the surface spike glycoprotein (S protein) of SARS-CoV-2, both at an overall resoln. of 2.9 angstroms, with a local resoln. of 3.5 angstroms at the ACE2-RBD interface. The ACE2-B0AT1 complex is assembled as a dimer of heterodimers, with the collectrin-like domain of ACE2 mediating homodimerization. The RBD is recognized by the extracellular peptidase domain of ACE2 mainly through polar residues. These findings provide important insights into the mol. basis for coronavirus recognition and infection.
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14Chan, W. C. W. Nano Research for Covid-19. ACS Nano 2020, 14, 3719– 3720, DOI: 10.1021/acsnano.0c02540Google Scholar14https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXlvFeqt7s%253D&md5=11dd55b6b01c0b0ce2b175e2517cbe21Nano Research for COVID-19Chan, Warren C. W.ACS Nano (2020), 14 (4), 3719-3720CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)A review. In the fight against COVID-19, research and technol. development and deployment are our best weapons. Nano-technol. tools can be adapted to detect, to treat, and to prevent this disease. Our community has a chance to accelerate the translation of our developments and deploy nanotechnol. advances as frontline tools.
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15Farka, Z.; Juřík, T.; Kovář, D.; Trnková, L.; Skládal, P. Nanoparticle-Based Immunochemical Biosensors and Assays: Recent Advances and Challenges. Chem. Rev. 2017, 117, 9973– 10042, DOI: 10.1021/acs.chemrev.7b00037Google Scholar15https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXht1eku7bI&md5=061b2561dfd603764c0250ac22c6e7d5Nanoparticle-Based Immunochemical Biosensors and Assays: Recent Advances and ChallengesFarka, Zdenek; Jurik, Tomas; Kovar, David; Trnkova, Libuse; Skladal, PetrChemical Reviews (Washington, DC, United States) (2017), 117 (15), 9973-10042CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review. The authors review the progress achieved during the recent five years in immunochem. biosensors (immunosensors) combined with nanoparticles for enhanced sensitivity. The initial part introduces antibodies as classic recognition elements. The optical sensing part describes fluorescent, luminescent, and surface plasmon resonance systems. Amperometry, voltammetry, and impedance spectroscopy represent electrochem. transducers; electrochemiluminescence with photoelec. conversion constitute widely used combined methods. The transducing options function together with suitable nanoparticles: metallic and metal oxides including magnetic ones, carbon-based nanotubes, graphene variants and luminescent carbon dots, nanocrystals as quantum dots, and photon up-converting particles. These sources merged together provide extreme variability of existing nanoimmunosensing options. Finally, applications in clin. anal. are summarized: markers, tumor cells, and pharmaceuticals; the detection of pathogenic microorganisms, toxic agents, and pesticides in the environmental field and food products.
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16Patra, J. K.; Das, G.; Fraceto, L. F.; Campos, E. V. R.; Rodriguez-Torres, M. d. P.; Acosta-Torres, L. S.; Diaz-Torres, L. A.; Grillo, R.; Swamy, M. K.; Sharma, S.; Habtemariam, S.; Shin, H.-S. Nano Based Drug Delivery Systems: Recent Developments and Future Prospects. J. Nanobiotechnol. 2018, 16, 71, DOI: 10.1186/s12951-018-0392-8Google Scholar16https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXjt1OisL4%253D&md5=a097a21379cd48333d81dffd7c57122fNano based drug delivery systems: recent developments and future prospectsPatra, Jayanta Kumar; Das, Gitishree; Fraceto, Leonardo Fernandes; Campos, Estefania Vangelie Ramos; Rodriguez-Torres, Maria Del Pilar; Acosta-Torres, Laura Susana; Diaz-Torres, Luis Armando; Grillo, Renato; Swamy, Mallappa Kumara; Sharma, Shivesh; Habtemariam, Solomon; Shin, Han-SeungJournal of Nanobiotechnology (2018), 16 (), 71/1-71/33CODEN: JNOAAO; ISSN:1477-3155. (BioMed Central Ltd.)A review. Nanomedicine and nano delivery systems are a relatively new but rapidly developing science where materials in the nanoscale range are employed to serve as means of diagnostic tools or to deliver therapeutic agents to specific targeted sites in a controlled manner. Nanotechnol. offers multiple benefits in treating chronic human diseases by site-specific, and target-oriented delivery of precise medicines. Recently, there are a no. of outstanding applications of the nanomedicine (chemotherapeutic agents, biol. agents, immunotherapeutic agents etc.) in the treatment of various diseases. The current review, presents an updated summary of recent advances in the field of nanomedicines and nano based drug delivery systems through comprehensive scrutiny of the discovery and application of nanomaterials in improving both the efficacy of novel and old drugs (e.g., natural products) and selective diagnosis through disease marker mols. The opportunities and challenges of nanomedicines in drug delivery from synthetic/natural sources to their clin. applications are also discussed. In addn., we have included information regarding the trends and perspectives in nanomedicine area.
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17Han, X.; Xu, K.; Taratula, O.; Farsad, K. Applications of Nanoparticles in Biomedical Imaging. Nanoscale 2019, 11, 799– 819, DOI: 10.1039/C8NR07769JGoogle Scholar17https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXisFyntbjP&md5=745795b26400f75c3ac09cf12bb15367Applications of nanoparticles in biomedical imagingHan, Xiangjun; Xu, Ke; Taratula, Olena; Farsad, KhashayarNanoscale (2019), 11 (3), 799-819CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)An urgent need for early detection and diagnosis of diseases continuously pushes the advancements of imaging modalities and contrast agents. Current challenges remain for fast and detailed imaging of tissue microstructures and lesion characterization that could be achieved via development of nontoxic contrast agents with longer circulation time. Nanoparticle technol. offers this possibility. Here, we review nanoparticle-based contrast agents employed in most common biomedical imaging modalities, including fluorescence imaging, MRI, CT, US, PET and SPECT, addressing their structure related features, advantages and limitations. Furthermore, their applications in each imaging modality are also reviewed using commonly studied examples. Future research will investigate multifunctional nanoplatforms to address safety, efficacy and theranostic capabilities. Nanoparticles as imaging contrast agents have promise to greatly benefit clin. practice.
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18Canaparo, R.; Foglietta, F.; Giuntini, F.; Della Pepa, C.; Dosio, F.; Serpe, L. Recent Developments in Antibacterial Therapy: Focus on Stimuli-Responsive Drug-Delivery Systems and Therapeutic Nanoparticles. Molecules 2019, 24, 1991, DOI: 10.3390/molecules24101991Google Scholar18https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtlemsbvF&md5=f073f7c2edf7816e82e3a707684a7f39Recent developments in antibacterial therapy: focus on stimuli-responsive drug-delivery systems and therapeutic nanoparticlesCanaparo, Roberto; Foglietta, Federica; Giuntini, Francesca; Della Pepa, Carlo; Dosio, Franco; Serpe, LoredanaMolecules (2019), 24 (10), 1991CODEN: MOLEFW; ISSN:1420-3049. (MDPI AG)A review. Conventional drugs used for antibacterial therapy display several limitations. This is not due to antibiotics being ineffective, but rather due to their low bioavailability, limited penetration to sites of infection and the rise of drug-resistant bacteria. Although new delivery systems (e.g., nanoparticles) that are loaded with antibacterial drugs have been designed to overcome these limitations, therapeutic efficacy does not seem to have improved. Against this backdrop, stimuli-responsive antibiotic-loaded nanoparticles and materials with antimicrobial properties (nanoantibiotics) present the ability to enhance therapeutic efficacy, while also reducing drug resistance and side effects. These stimuli can either be exogenous (e.g., light, ultrasound) or endogenous (e.g., pH, variation in redox gradient, enzymes). This promising therapeutic approach relies on advances in materials science and increased knowledge of microorganism growth and biofilm formation. This review provides an overview in the field of antibacterial drug-delivery systems and nanoantibiotics that benefit from a response to specific triggers, and also presents a no. of future prospects.
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19Chen, L.; Liang, J. An Overview of Functional Nanoparticles as Novel Emerging Antiviral Therapeutic Agents. Mater. Sci. Eng., C 2020, 112, 110924, DOI: 10.1016/j.msec.2020.110924Google Scholar19https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXnt1WgsLc%253D&md5=ea6cd71a6a0aefb400c1af8331f8c05eAn overview of functional nanoparticles as novel emerging antiviral therapeutic agentsChen, Lu; Liang, JiangongMaterials Science & Engineering, C: Materials for Biological Applications (2020), 112 (), 110924CODEN: MSCEEE; ISSN:0928-4931. (Elsevier B.V.)A review. Research on highly effective antiviral drugs is essential for preventing the spread of infections and reducing losses. Recently, many functional nanoparticles have been shown to possess remarkable antiviral ability, such as quantum dots, gold and silver nanoparticles, nanoclusters, carbon dots, graphene oxide, silicon materials, polymers and dendrimers. Despite their difference in antiviral mechanism and inhibition efficacy, these functional nanoparticles-based structures have unique features as potential antiviral candidates. In this topical review, we highlight the antiviral efficacy and mechanism of these nanoparticles. Specifically, we introduce various methods for analyzing the viricidal activity of functional nanoparticles and the latest advances in antiviral functional nanoparticles. Furthermore, we systematically describe the advantages and disadvantages of these functional nanoparticles in viricidal applications. Finally, we discuss the challenges and prospects of antiviral nanostructures. This topic review covers 132 papers and will enrich our knowledge about the antiviral efficacy and mechanism of various functional nanoparticles.
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20Park, J.-E.; Kim, K.; Jung, Y.; Kim, J.-H.; Nam, J.-M. Metal Nanoparticles for Virus Detection. ChemNanoMat 2016, 2, 927– 936, DOI: 10.1002/cnma.201600165Google Scholar20https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xhs1CltrvE&md5=af4c982ee1e5180948d3e6902f17a3ccMetal Nanoparticles for Virus DetectionPark, Jeong-Eun; Kim, Keunsuk; Jung, Yoonjae; Kim, Jae-Ho; Nam, Jwa-MinChemNanoMat (2016), 2 (10), 927-936CODEN: CHEMSB; ISSN:2199-692X. (Wiley-VCH Verlag GmbH & Co. KGaA)Viruses are small agents that can infect living creatures and cause harmful diseases. Rapid, sensitive virus detection would be beneficial for public health, and recent studies have shown that nanoparticles may have applications in virus detection. In particular, the unique properties of metal nanoparticles, originating from localized surface plasmons, allow for detection of virus through various methods. Addnl., the high surface-to-vol. ratio and ease of surface modification of these nanoparticles provide advantages for bio-applications. In this Focus Review, we describe currently available and recent advances in virus detection methods with metal nanoparticles. First, we outline several features of traditional virus detection methods and provide a brief explanation of metal nanoparticles. Then, we discuss soln.-based or substrate-based virus detection according to the main operating phase of the detection elements. Finally, we evaluate the use of clin. samples for virus detection with metal nanoparticles.
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21Corman, V. M.; Landt, O.; Kaiser, M.; Molenkamp, R.; Meijer, A.; Chu, D. K.; Bleicker, T.; Brünink, S.; Schneider, J.; Schmidt, M. L.; Mulders, D. G.; Haagmans, B. L.; van der Veer, B.; van den Brink, S.; Wijsman, L.; Goderski, G.; Romette, J.-L.; Ellis, J.; Zambon, M.; Peiris, M.; Goossens, H.; Reusken, C.; Koopmans, M. P.; Drosten, C. Detection of 2019 Novel Coronavirus (2019-nCoV) by Real-Time RT-PCR. Euro Surveill. 2020, 25, 2000045, DOI: 10.2807/1560-7917.ES.2020.25.3.2000045Google ScholarThere is no corresponding record for this reference.
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22Shen, M.; Zhou, Y.; Ye, J.; Abdullah Al-Maskri, A. A.; Kang, Y.; Zeng, S.; Cai, S. Recent Advances and Perspectives of Nucleic Acid Detection for Coronavirus. J. Pharm. Anal. 2020, 10, 97– 101, DOI: 10.1016/j.jpha.2020.02.010Google Scholar22https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB38zlsVGgug%253D%253D&md5=345f4c6314a6a890a0b3b365df819d6bRecent advances and perspectives of nucleic acid detection for coronavirusShen Minzhe; Zhou Ying; Ye Jiawei; Abdullah Al-Maskri Abdu Ahmed; Kang Yu; Zeng Su; Cai ShengJournal of pharmaceutical analysis (2020), 10 (2), 97-101 ISSN:.The recent pneumonia outbreak caused by a novel coronavirus (SARS-CoV-2) is posing a great threat to global public health. Therefore, rapid and accurate identification of pathogenic viruses plays a vital role in selecting appropriate treatments, saving people's lives and preventing epidemics. It is important to establish a quick standard diagnostic test for the detection of the infectious disease (COVID-19) to prevent subsequent secondary spread. Polymerase chain reaction (PCR) is regarded as a gold standard test for the molecular diagnosis of viral and bacterial infections with high sensitivity and specificity. Isothermal nucleic acid amplification is considered to be a highly promising candidate method due to its fundamental advantage in quick procedure time at constant temperature without thermocycler operation. A variety of improved or new approaches also have been developed. This review summarizes the currently available detection methods for coronavirus nucleic acid. It is anticipated that this will assist researchers and clinicians in developing better techniques for timely and effective detection of coronavirus infection.
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23Emery, S. L.; Erdman, D. D.; Bowen, M. D.; Newton, B. R.; Winchell, J. M.; Meyer, R. F.; Tong, S.; Cook, B. T.; Holloway, B. P.; McCaustland, K. A.; Rota, P. A.; Bankamp, B.; Lowe, L. E.; Ksiazek, T. G.; Bellini, W. J.; Anderson, L. J. Real-Time Reverse Transcription-Polymerase Chain Reaction Assay for SARS-Associated Coronavirus. Emerging Infect. Dis. 2004, 10, 311– 316, DOI: 10.3201/eid1002.030759Google Scholar23https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXitVSjt7Y%253D&md5=4b670d95bd413a49fd3e2a76f41c85ecReal-time reverse transcription-polymerase chain reaction assay for SARS-associated coronavirusEmery, Shannon L.; Erdman, Dean D.; Bowen, Michael D.; Newton, Bruce R.; Winchell, Jonas M.; Meyer, Richard F.; Tong, Suxiang; Cook, Byron T.; Holloway, Brian P.; McCaustland, Karen A.; Rota, Paul A.; Bankamp, Bettina; Lowe, Luis E.; Ksiazek, Tom G.; Bellini, William J.; Anderson, Larry J.Emerging Infectious Diseases (2004), 10 (2), 311-316CODEN: EIDIFA; ISSN:1080-6040. (National Center for Infectious Diseases, Centers for Disease Control and Prevention)A real-time reverse transcription-polymerase chain reaction (RT-PCR) assay was developed to rapidly detect the severe acute respiratory syndrome-assocd. coronavirus (SARS-CoV). The assay, based on multiple primer and probe sets located in different regions of the SARS-CoV genome, could discriminate SARS-CoV from other human and animal coronaviruses with a potential detection limit of <10 genomic copies per reaction. The real-time RT-PCR assay was more sensitive than a conventional RT-PCR assay or culture isolation and proved suitable to detect SARS-CoV in clin. specimens. Application of this assay will aid in diagnosing SARS-CoV infection.
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24Zhang, Y.; Qu, S.; Xu, L. Progress in the Study of Virus Detection Methods: The Possibility of Alternative Methods to Validate Virus Inactivation. Biotechnol. Bioeng. 2019, 116, 2095– 2102, DOI: 10.1002/bit.27003Google Scholar24https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtVGgsb%252FN&md5=7151503fe2cf3942d85fd0ecfbd402e7Progress in the study of virus detection methods: The possibility of alternative methods to validate virus inactivationZhang, Yu; Qu, Shuxin; Xu, LimingBiotechnology and Bioengineering (2019), 116 (8), 2095-2102CODEN: BIBIAU; ISSN:0006-3592. (John Wiley & Sons, Inc.)Virus inactivation validation studies have been widely applied in the risk assessment of biogenic material-based medical products, such as biol. products, animal tissue-derived biomaterials, and allogeneic biomaterials, to decrease the risk of virus transmission. Traditional virus detection methods in an inactivation validation study utilize cell culture as a tool to quantify the infectious virus by observing cytopathic effects (CPEs) after virus inactivation. However, this is susceptible to subjective factors because CPEs must be obsd. by experts under a microscope during virus titrn. In addn., this method is costly and time- and labor-consuming. Mol. biol. technologies such as quant. polymerase chain reaction (qPCR) have been widely used for virus detection but cannot distinguish infectious and noninfectious viruses. Therefore, qPCR cannot be directly applied to virus inactivation validation studies. In this paper, methods to detect viruses and progress in the challenge of differentiating infectious and noninfectious viruses with the combination of pretreatment and qPCR techniques such as the integrated cell culture-qPCR (ICC-qPCR) method are reviewed. In addn., the advantages and disadvantages of each new method, as well as its prospect in virus inactivation validation studies, are discussed.
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25Fukushi, S.; Fukuma, A.; Kurosu, T.; Watanabe, S.; Shimojima, M.; Shirato, K.; Iwata-Yoshikawa, N.; Nagata, N.; Ohnishi, K.; Ato, M.; Melaku, S. K.; Sentsui, H.; Saijo, M. Characterization of Novel Monoclonal Antibodies against the MERS-Coronavirus Spike Protein and Their Application in Species-Independent Antibody Detection by Competitive Elisa. J. Virol. Methods 2018, 251, 22– 29, DOI: 10.1016/j.jviromet.2017.10.008Google Scholar25https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhs1elur3F&md5=cc5ae2c729927e50904fb962e209c8f8Characterization of novel monoclonal antibodies against the MERS-coronavirus spike protein and their application in species-independent antibody detection by competitive ELISAFukushi, Shuetsu; Fukuma, Aiko; Kurosu, Takeshi; Watanabe, Shumpei; Shimojima, Masayuki; Shirato, Kazuya; Iwata-Yoshikawa, Naoko; Nagata, Noriyo; Ohnishi, Kazuo; Ato, Manabu; Melaku, Simenew Keskes; Sentsui, Hiroshi; Saijo, MasayukiJournal of Virological Methods (2018), 251 (), 22-29CODEN: JVMEDH; ISSN:0166-0934. (Elsevier B.V.)Since discovering the Middle East respiratory syndrome coronavirus (MERS-CoV) as a causative agent of severe respiratory illness in the Middle East in 2012, serol. testing has been conducted to assess antibody responses in patients and to investigate the zoonotic reservoir of the virus. Although the virus neutralization test is the gold std. assay for MERS diagnosis and for investigating the zoonotic reservoir, it uses live virus and so must be performed in high containment labs. Competitive ELISA (cELISA), in which a labeled monoclonal antibody (MAb) competes with test serum antibodies for target epitopes, may be a suitable alternative because it detects antibodies in a species-independent manner. In this study, novel MAbs against the spike protein of MERS-CoV were produced and characterized. One of these MAbs was used to develop a cELISA. The cELISA detected MERS-CoV-specific antibodies in sera from MERS-CoV-infected rats and rabbits immunized with the spike protein of MERS-CoV. The MAb-based cELISA was validated using sera from Ethiopian dromedary camels. Relative to the neutralization test, the cELISA detected MERS-CoV-specific antibodies in 66 Ethiopian dromedary camels with a sensitivity and specificity of 98% and 100%, resp. The cELISA and neutralization test results correlated well (Pearson's correlation coeffs. = 0.71-0.76, depending on the cELISA serum diln.). This cELISA may be useful for MERS epidemiol. investigations on MERS-CoV infection.
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26Mokhtarzadeh, A.; Eivazzadeh-Keihan, R.; Pashazadeh, P.; Hejazi, M.; Gharaatifar, N.; Hasanzadeh, M.; Baradaran, B.; de la Guardia, M. Nanomaterial-Based Biosensors for Detection of Pathogenic Virus. TrAC, Trends Anal. Chem. 2017, 97, 445– 457, DOI: 10.1016/j.trac.2017.10.005Google Scholar26https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhslagtbnE&md5=37de1c8ce7bc63421d640769e8676fafNanomaterial-based biosensors for detection of pathogenic virusMokhtarzadeh, Ahad; Eivazzadeh-Keihan, Reza; Pashazadeh, Paria; Hejazi, Maryam; Gharaatifar, Nasrin; Hasanzadeh, Mohammad; Baradaran, Behzad; de la Guardia, MiguelTrAC, Trends in Analytical Chemistry (2017), 97 (), 445-457CODEN: TTAEDJ; ISSN:0165-9936. (Elsevier B.V.)Viruses are real menace to human safety that cause devastating viral disease. The high prevalence of these diseases is due to improper detecting tools. Therefore, there is a remarkable demand to identify viruses in a fast, selective and accurate way. Several biosensors have been designed and commercialized for detection of pathogenic viruses. However, they present many challenges. Nanotechnol. overcomes these challenges and performs direct detection of mol. targets in real time. In this overview, studies concerning nanotechnol.-based biosensors for pathogenic virus detection have been summarized, paying special attention to biosensors based on graphene oxide, silica, carbon nanotubes, gold, silver, zinc oxide and magnetic nanoparticles, which could pave the way to detect viral diseases and provide healthy life for infected patients.
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27Li, H.; Rothberg, L. Colorimetric Detection of DNA Sequences Based on Electrostatic Interactions with Unmodified Gold Nanoparticles. Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 14036– 14039, DOI: 10.1073/pnas.0406115101Google Scholar27https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXosVylsrY%253D&md5=c63574b39b9b5b82007779183959a55bColorimetric detection of DNA sequences based on electrostatic interactions with unmodified gold nanoparticlesLi, Huixiang; Rothberg, LewisProceedings of the National Academy of Sciences of the United States of America (2004), 101 (39), 14036-14039CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)We find that single- and double-stranded oligonucleotides have different propensities to adsorb on gold nanoparticles in colloidal soln. We use this observation to design a hybridization assay based on color changes assocd. with gold aggregation. Because the underlying adsorption mechanism is electrostatic, no covalent functionalization of the gold, the probe, or the target DNA is required. Hybridization conditions can be optimized because it is completely sepd. from the detection step. The assay is complete within 5 min, and < 100 fmol of target produces color changes observable without instrumentation. Single-base-pair mismatches are easily detected.
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28Kim, H.; Park, M.; Hwang, J.; Kim, J. H.; Chung, D.-R.; Lee, K.-s.; Kang, M. Development of Label-Free Colorimetric Assay for MERS-CoV Using Gold Nanoparticles. ACS Sens. 2019, 4, 1306– 1312, DOI: 10.1021/acssensors.9b00175Google Scholar28https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXovVKmsL0%253D&md5=8b0c7c510447ec91d809317e915ffddaDevelopment of Label-Free Colorimetric Assay for MERS-CoV Using Gold NanoparticlesKim, Hanbi; Park, Minseon; Hwang, Joonki; Kim, Jin Hwa; Chung, Doo-Ryeon; Lee, Kyu-sung; Kang, MinheeACS Sensors (2019), 4 (5), 1306-1312CODEN: ASCEFJ; ISSN:2379-3694. (American Chemical Society)Worldwide outbreaks of infectious diseases necessitate the development of rapid and accurate diagnostic methods. Colorimetric assays are a representative tool to simply identify the target mols. in specimens through color changes of an indicator (e.g., nanosized metallic particle, and dye mols.). The detection method is used to confirm the presence of biomarkers visually and measure absorbance of the colored compds. at a specific wavelength. In this study, we propose a colorimetric assay based on an extended form of double-stranded DNA (dsDNA) self-assembly shielded gold nanoparticles (AuNPs) under pos. electrolyte (e.g., 0.1 M MgCl2) for detection of Middle East respiratory syndrome coronavirus (MERS-CoV). This platform is able to verify the existence of viral mols. through a localized surface plasmon resonance (LSPR) shift and color changes of AuNPs in the UV-vis wavelength range. We designed a pair of thiol-modified probes at either the 5' end or 3' end to organize complementary base pairs with upstream of the E protein gene (upE) and open reading frames (ORF) 1a on MERS-CoV. The dsDNA of the target and probes forms a disulfide-induced long self-assembled complex, which protects AuNPs from salt-induced aggregation and transition of optical properties. This colorimetric assay could discriminate down to 1 pmol/μL of 30 bp MERS-CoV and further be adapted for convenient on-site detection of other infectious diseases, esp. in resource-limited settings.
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29Huang, P.; Wang, H.; Cao, Z.; Jin, H.; Chi, H.; Zhao, J.; Yu, B.; Yan, F.; Hu, X.; Wu, F.; Jiao, C.; Hou, P.; Xu, S.; Zhao, Y.; Feng, N.; Wang, J.; Sun, W.; Wang, T.; Gao, Y.; Yang, S.; Xia, X. A Rapid and Specific Assay for the Detection of MERS-CoV. Front. Microbiol. 2018, 9, 1101, DOI: 10.3389/fmicb.2018.01101Google Scholar29https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1Mbms12itg%253D%253D&md5=ffdd4aeb8606a2047bda6e5a10536e6aA Rapid and Specific Assay for the Detection of MERS-CoVHuang Pei; Hu Xingxing; Xu Shengnan; Wang Jianzhong; Huang Pei; Wang Hualei; Cao Zengguo; Jin Hongli; Chi Hang; Yan Feihu; Hu Xingxing; Wu Fangfang; Jiao Cuicui; Hou Pengfei; Xu Shengnan; Zhao Yongkun; Feng Na; Sun Weiyang; Wang Tiecheng; Gao Yuwei; Yang Songtao; Xia Xianzhu; Wang Hualei; Cao Zengguo; Jin Hongli; Hou Pengfei; Wang Hualei; Zhao Yongkun; Feng Na; Sun Weiyang; Wang Tiecheng; Gao Yuwei; Yang Songtao; Xia Xianzhu; Zhao Jincun; Zhao Jincun; Yu BeibeiFrontiers in microbiology (2018), 9 (), 1101 ISSN:1664-302X.Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel human coronavirus that can cause human respiratory disease. The development of a detection method for this virus that can lead to rapid and accurate diagnosis would be significant. In this study, we established a nucleic acid visualization technique that combines the reverse transcription loop-mediated isothermal amplification technique and a vertical flow visualization strip (RT-LAMP-VF) to detect the N gene of MERS-CoV. The RT-LAMP-VF assay was performed in a constant temperature water bath for 30 min, and the result was visible by the naked eye within 5 min. The RT-LAMP-VF assay was capable of detecting 2 × 10(1) copies/μl of synthesized RNA transcript and 1 × 10(1) copies/μl of MERS-CoV RNA. The method exhibits no cross-reactivities with multiple CoVs including SARS-related (SARSr)-CoV, HKU4, HKU1, OC43 and 229E, and thus exhibits high specificity. Compared to the real-time RT-PCR (rRT-PCR) method recommended by the World Health Organization (WHO), the RT-LAMP-VF assay is easy to handle, does not require expensive equipment and can rapidly complete detection within 35 min.
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30Moitra, P.; Alafeef, M.; Dighe, K.; Frieman, M. B.; Pan, D. Selective Naked-Eye Detection of SARS-CoV-2 Mediated by N Gene Targeted Antisense Oligonucleotide Capped Plasmonic Nanoparticles. ACS Nano 2020, 14, 7617– 7627, DOI: 10.1021/acsnano.0c03822Google Scholar30https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXpvVGktLc%253D&md5=6edff96bd5fecfeac6bb14b777f4c066Selective Naked-Eye Detection of SARS-CoV-2 Mediated by N Gene Targeted Antisense Oligonucleotide Capped Plasmonic NanoparticlesMoitra, Parikshit; Alafeef, Maha; Dighe, Ketan; Frieman, Matthew B.; Pan, DipanjanACS Nano (2020), 14 (6), 7617-7627CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)The current outbreak of the pandemic coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) demands its rapid, convenient, and large-scale diagnosis to downregulate its spread within as well as across the communities. But the reliability, reproducibility, and selectivity of majority of such diagnostic tests fail when they are tested either to a viral load at its early representation or to a viral gene mutated during its current spread. In this regard, a selective "naked-eye" detection of SARS-CoV-2 is highly desirable, which can be tested without accessing any advanced instrumental techniques. We herein report the development of a colorimetric assay based on gold nanoparticles (AuNPs), when capped with suitably designed thiol-modified antisense oligonucleotides (ASOs) specific for N-gene (nucleocapsid phosphoprotein) of SARS-CoV-2, could be used for diagnosing pos. COVID-19 cases within 10 min from the isolated RNA samples. The thiol-modified ASO-capped AuNPs agglomerate selectively in the presence of its target RNA sequence of SARS-CoV-2 and demonstrate a change in its surface plasmon resonance. Further, the addn. of RNaseH cleaves the RNA strand from the RNA-DNA hybrid leading to a visually detectable ppt. from the soln. mediated by the addnl. agglomeration among the AuNPs. The selectivity of the assay has been monitored in the presence of MERS-CoV viral RNA with a limit of detection of 0.18 ng/μL of RNA having SARS-CoV-2 viral load. Thus, the current study reports a selective and visual "naked-eye" detection of COVID-19 causative virus, SARS-CoV-2, without the requirement of any sophisticated instrumental techniques.
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31Layqah, L. A.; Eissa, S. An Electrochemical Immunosensor for the Corona Virus Associated with the Middle East Respiratory Syndrome Using an Array of Gold Nanoparticle-Modified Carbon Electrodes. Microchim. Acta 2019, 186, 224, DOI: 10.1007/s00604-019-3345-5Google ScholarThere is no corresponding record for this reference.
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32Lee, Y.; Kang, B.-H.; Kang, M.; Chung, D. R.; Yi, G.-S.; Lee, L. P.; Jeong, K.-H. Nanoplasmonic on-Chip PCR for Rapid Precision Molecular Diagnostics. ACS Appl. Mater. Interfaces 2020, 12, 12533– 12540, DOI: 10.1021/acsami.9b23591Google Scholar32https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXjvVGltr4%253D&md5=8c15061f8e85afa6a82e86b47cb40866Nanoplasmonic on-Chip PCR for rapid precision molecular diagnosticsLee, Youngseop; Kang, Byoung-Hoon; Kang, Minhee; Chung, Doo Ryeon; Yi, Gwan-Su; Lee, Luke P.; Jeong, Ki-HunACS Applied Materials & Interfaces (2020), 12 (11), 12533-12540CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Emerging mol. diagnosis requires ultrafast polymerase chain reaction (PCR) on chip for rapid precise detection of infectious diseases in the point-of-care test. Here, we report nanoplasmonic on-chip PCR for rapid precision mol. diagnostics. The nanoplasmonic pillar arrays (NPA) comprise gold nanoislands on the top and sidewall of large-scale glass nanopillar arrays. The nanoplasmonic pillars enhance light absorption of a white light-emitting diode (LED) over the whole visible range due to strong electromagnetic hotspots between the nanoislands. As a result, they effectively induce photothermal heating for ultrafast PCR thermal cycling. The temp. profile of NPA exhibits 30 cycles between 98 and 60°C for a total of 3 min and 30 s during the cyclic excitation of white LED light. The exptl. results also demonstrate the rapid DNA amplification of both 0.1 ng μL-1 of λ-DNA in 20 thermal cycles and 0.1 ng μL-1 of complementary DNA of Middle East respiratory syndrome coronavirus in 30 thermal cycles using a conventional PCR vol. of 15μL. This nanoplasmonic PCR technique provides a new opportunity for rapid precision mol. diagnostics.
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33Teengam, P.; Siangproh, W.; Tuantranont, A.; Vilaivan, T.; Chailapakul, O.; Henry, C. S. Multiplex Paper-Based Colorimetric DNA Sensor Using Pyrrolidinyl Peptide Nucleic Acid-Induced AgNPs Aggregation for Detecting MERS-CoV, MTB, and HPV Oligonucleotides. Anal. Chem. 2017, 89, 5428– 5435, DOI: 10.1021/acs.analchem.7b00255Google Scholar33https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXlvVGkt7Y%253D&md5=804791a1596c35f834173a36be8eefc1Multiplex Paper-Based Colorimetric DNA Sensor Using Pyrrolidinyl Peptide Nucleic Acid-Induced AgNPs Aggregation for Detecting MERS-CoV, MTB, and HPV OligonucleotidesTeengam, Prinjaporn; Siangproh, Weena; Tuantranont, Adisorn; Vilaivan, Tirayut; Chailapakul, Orawon; Henry, Charles S.Analytical Chemistry (Washington, DC, United States) (2017), 89 (10), 5428-5435CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)The development of simple fluorescent and colorimetric assays that enable point-of-care DNA and RNA detection has been a topic of significant research because of the utility of such assays in resource limited settings. The most common motifs utilize hybridization to a complementary detection strand coupled with a sensitive reporter mol. Here, a paper-based colorimetric assay for DNA detection based on pyrrolidinyl peptide nucleic acid (acpcPNA)-induced nanoparticle aggregation is reported as an alternative to traditional colorimetric approaches. PNA probes are an attractive alternative to DNA and RNA probes because they are chem. and biol. stable, easily synthesized, and hybridize efficiently with the complementary DNA strands. The acpcPNA probe contains a single pos. charge from the lysine at C-terminus and causes aggregation of citrate anion-stabilized silver nanoparticles (AgNPs) in the absence of complementary DNA. In the presence of target DNA, formation of the anionic DNA-acpcPNA duplex results in dispersion of the AgNPs as a result of electrostatic repulsion, giving rise to a detectable color change. Factors affecting the sensitivity and selectivity of this assay were investigated, including ionic strength, AgNP concn., PNA concn., and DNA strand mismatches. The method was used for screening of synthetic Middle East respiratory syndrome coronavirus (MERS-Co-V), mycobacterium tuberculosis (MTB) and human papillomavirus (HPV)DNA based on a colorimetric paper-based anal. device developed using the aforementioned principle. The oligonucleotide targets were detected by measuring the color change of AgNPs, giving detection limits of 1.53 nM (MERS-Co-V), 1.27 nM (MTB) and 1.03 nM (HPV). The acpcPNA probe exhibited high selectivity for the complementary oligonucleotides over single-base-mismatch, two-base-mismatch and noncomplementary DNA targets. The proposed paper-based colorimetric DNA sensor has potential to be an alternative approach for simple, rapid, sensitive and selective DNA detection.
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34Gong, P.; He, X.; Wang, K.; Tan, W.; Xie, W.; Wu, P.; Li, H. Combination of Functionalized Nanoparticles and Polymerase Chain Reaction-Based Method for SARS-CoV Gene Detection. J. Nanosci. Nanotechnol. 2008, 8, 293– 300, DOI: 10.1166/jnn.2008.18130Google Scholar34https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXnsVamuro%253D&md5=50c4b12d716b46a58c9bbde0c8c54b9aCombination of functionalized nanoparticles and polymerase chain reaction-based method for SARS-CoV gene detectionGong, Ping; He, Xiaoxiao; Wang, Kemin; Tan, Weihong; Xie, Wengang; Wu, Ping; Li, HuiminJournal of Nanoscience and Nanotechnology (2008), 8 (1), 293-300CODEN: JNNOAR; ISSN:1533-4880. (American Scientific Publishers)Rapid and sensitive detection of SARS assocd. coronavirus is crit. for early diagnosis and control of severe acute respiratory syndrome. This study describes a method for the detection of SARS assocd. coronavirus gene by the combination of functionalized nanoparticles and PCR-based assay. In this method, the target cDNA of SARS assocd. coronavirus was firstly captured and enriched from the mixt. of target cDNA and non-target cDNA by the use of the functionalized silica coated superparamagnetic nanoparticles. Addnl., the enriched target cDNA were amplified through a general symmetry PCR and then was selectively isolated from the double strands PCR products by applying the silica coated superparamagnetic nanoparticles again. Finally, we detected the amplified target cDNA by employing the functionalized silica coated fluorescent nanoparticles as signaling probes with a sandwich hybridization format. The results show that the target cDNA can be assayed successfully with a detection limit of 2.0 × 103 copies and the nonspecific amplification could be inhibited. In addn., the detection procedure is rapid and can be completed in less than 6 h. Our results suggest that this approach will provide promising prospects for other pathogens detection.
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35Zhao, Z.; Cui, H.; Song, W.; Ru, X.; Zhou, W.; Yu, X. A Simple Magnetic Nanoparticles-Based Viral RNA Extraction Method for Efficient Detection of SARS-CoV-2. BioRxiv 2020.Google ScholarThere is no corresponding record for this reference.
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36Roh, C.; Jo, S. K. Quantitative and Sensitive Detection of SARS Coronavirus Nucleocapsid Protein Using Quantum Dots-Conjugated RNA Aptamer on Chip. J. Chem. Technol. Biotechnol. 2011, 86, 1475– 1479, DOI: 10.1002/jctb.2721Google Scholar36https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhsVCnur%252FP&md5=9668cddb8cf8245fc558f83f3b44e426Quantitative and sensitive detection of SARS coronavirus nucleocapsid protein using quantum dots-conjugated RNA aptamer on chipRoh, Changhyun; Jo, Sung KeeJournal of Chemical Technology and Biotechnology (2011), 86 (12), 1475-1479CODEN: JCTBED; ISSN:0268-2575. (John Wiley & Sons Ltd.)Globally, severe acute respiratory syndrome coronavirus (SARS-CoV) is a newly emerging virus that causes SARS with high mortality rate in infected people. The nucleocapsid (N) protein of the severe acute respiratory syndrome (SARS)-assocd. coronavirus (SARS-CoV) is an important antigen for the early diagnosis of SARS and the detection of diseases. Here, a new quantum dots (QDs)-conjugated RNA aptamer with high sensitivity and rapidity is proposed for the detection of SARS-CoV N protein using an on chip system. A QDs-conjugated RNA aptamer can specifically hybridize on the immobilized SARS-CoV N protein on the surface of a glass chip. Detection is based on the optical signal variation of a QDs-supported RNA aptamer interacting on an immobilized protein chip. Using an optical QDs-based RNA aptamer chip, SARS N protein was detected at concns. as low as 0.1 pg mL-1. It was demonstrated that the QDs-conjugated RNA aptamer could interact on a designed chip specifically and sensitively. This device could form a QDs-conjugated biosensor prototype chip for SARS-CoV N protein diagnosis. The proposed visual SARS-CoV N protein detection technique may avoid the limitations of other reported methods because of its high sensitivity, good specificity, ease of use, and the ability to perform one-spot monitoring.
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37Ahmed, S. R.; Nagy, É.; Neethirajan, S. Self-Assembled Star-Shaped Chiroplasmonic Gold Nanoparticles for an Ultrasensitive Chiro-Immunosensor for Viruses. RSC Adv. 2017, 7, 40849– 40857, DOI: 10.1039/C7RA07175BGoogle Scholar37https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhsVers7zN&md5=1a4acbe1b3f14d5e1df0e41dcb264838Self-assembled star-shaped chiroplasmonic gold nanoparticles for an ultrasensitive chiro-immunosensor for virusesAhmed, Syed Rahin; Nagy, Eva; Neethirajan, SureshRSC Advances (2017), 7 (65), 40849-40857CODEN: RSCACL; ISSN:2046-2069. (Royal Society of Chemistry)Near field optics and optical tunneling light-matter interactions in the superstructure of chiral nanostructures and semiconductor quantum dots exhibit strong optical rotation activity that may open a new window for chiral-based bioanalyte detection. Herein we report an ultrasensitive, chiro-immunosensor using a superstructure of chiral gold nanohybrids (CAu NPs) and quantum dots (QDs). Self-assembly techniques were employed to create asym. plasmonic chiral nanostructures to extend the spectral range of the CD (CD) response to obtain superior plasmonic resonant coupling with the QD excited state; this may help to achieve lower limit of detection (LOD) values. As a result, the designed probe could detect avian influenza A (H5N1) viral concns. at the picomolar level, a significant improvement in sensitivity in comparison to a non-assembled CAu NP-based chiro-assay. The practicability of the proposed sensing system was successfully demonstrated on several virus cultures, including avian influenza A (H4N6) virus, fowl adenovirus and coronavirus in blood samples. The results of our study highlight that exciton-plasmon interactions change the chirality, and the use of self-assembled nanostructures is an efficient strategy for enhancing the sensitivity of plasmonic nanosensors.
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38Ahmed, S. R.; Kang, S. W.; Oh, S.; Lee, J.; Neethirajan, S. Chiral Zirconium Quantum Dots: A New Class of Nanocrystals for Optical Detection of Coronavirus. Heliyon 2018, 4, e00766, DOI: 10.1016/j.heliyon.2018.e00766Google ScholarThere is no corresponding record for this reference.
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39Fong, K. E.; Yung, L. -Y. L. Localized Surface Plasmon Resonance: A Unique Property of Plasmonic Nanoparticles for Nucleic Acid Detection. Nanoscale 2013, 5, 12043– 12071, DOI: 10.1039/c3nr02257aGoogle Scholar39https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhvVejurfI&md5=e47a2ed4060bd96422cbbad858226deeLocalized surface plasmon resonance: a unique property of plasmonic nanoparticles for nucleic acid detectionFong, Kah Ee; Yung, Lin-Yue LanryNanoscale (2013), 5 (24), 12043-12071CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)A review. Localized surface plasmon resonance (LSPR) of noble metal nanoparticles (a.k.a. plasmonic nanoparticles) opens up a new horizon for advanced biomol. sensing. However, an effective and practical sensing system still requires meticulous design to achieve good sensitivity and distinctive selectivity for routine use and high-throughput detection. In particular, the detection of DNA and RNA is crucial in biomedical research and clin. diagnostics. This review describes the fundamental aspects of LSPR and provides an overall account of how it is exploited to assist in nucleic acid sensing. The detection efficiency of each LSPR-based approach is assessed with respect to the assay design, the selection of plasmonic nanoparticles, and the choice of nucleic acid probes which influence the duplex hybridization. Judicious comparison is made among various LSPR-based approaches in terms of the assaying time, the sensitivity or lowest sensing concn. (i.e. limit of detection or LOD), and the single-base mismatch (SBM) selectivity.
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40Unser, S.; Bruzas, I.; He, J.; Sagle, L. Localized Surface Plasmon Resonance Biosensing: Current Challenges and Approaches. Sensors 2015, 15, 15684– 15716, DOI: 10.3390/s150715684Google Scholar40https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC28%252FgslGhtg%253D%253D&md5=32c09c56423b729c1928124f8300131fLocalized Surface Plasmon Resonance Biosensing: Current Challenges and ApproachesUnser Sarah; Bruzas Ian; He Jie; Sagle LauraSensors (Basel, Switzerland) (2015), 15 (7), 15684-716 ISSN:.Localized surface plasmon resonance (LSPR) has emerged as a leader among label-free biosensing techniques in that it offers sensitive, robust, and facile detection. Traditional LSPR-based biosensing utilizes the sensitivity of the plasmon frequency to changes in local index of refraction at the nanoparticle surface. Although surface plasmon resonance technologies are now widely used to measure biomolecular interactions, several challenges remain. In this article, we have categorized these challenges into four categories: improving sensitivity and limit of detection, selectivity in complex biological solutions, sensitive detection of membrane-associated species, and the adaptation of sensing elements for point-of-care diagnostic devices. The first section of this article will involve a conceptual discussion of surface plasmon resonance and the factors affecting changes in optical signal detected. The following sections will discuss applications of LSPR biosensing with an emphasis on recent advances and approaches to overcome the four limitations mentioned above. First, improvements in limit of detection through various amplification strategies will be highlighted. The second section will involve advances to improve selectivity in complex media through self-assembled monolayers, "plasmon ruler" devices involving plasmonic coupling, and shape complementarity on the nanoparticle surface. The following section will describe various LSPR platforms designed for the sensitive detection of membrane-associated species. Finally, recent advances towards multiplexed and microfluidic LSPR-based devices for inexpensive, rapid, point-of-care diagnostics will be discussed.
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41Srinoi, P.; Chen, Y.-T.; Vittur, V.; Marquez, M. D.; Lee, T. R. Bimetallic Nanoparticles: Enhanced Magnetic and Optical Properties for Emerging Biological Applications. Appl. Sci. 2018, 8, 1106, DOI: 10.3390/app8071106Google Scholar41https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhs1OgurnL&md5=258dcac5900eaf8f3bc9bd44e2a13855Bimetallic nanoparticles: enhanced magnetic and optical properties for emerging biological applicationsSrinoi, Pannaree; Chen, Yi-Ting; Vittur, Varadee; Marquez, Maria D.; Lee, T. RandallApplied Sciences (2018), 8 (7), 1106/1-1106/32CODEN: ASPCC7; ISSN:2076-3417. (MDPI AG)Metal nanoparticles are extensively studied due to their unique chem. and phys. properties, which differ from the properties of their resp. bulk materials. Likewise, the properties of heterogeneous bimetallic structures are far more attractive than those of single-component nanoparticles. For example, the incorporation of a second metal into a nanoparticle structure influences and can potentially enhance the optical/plasmonic and magnetic properties of the material. This review focuses on the enhanced optical/plasmonic and magnetic properties offered by bimetallic nanoparticles and their corresponding impact on biol. applications. In this review, we summarize the predominant structures of bimetallic nanoparticles, outline their synthesis methods, and highlight their use in biol. applications, both diagnostic and therapeutic, which are dictated by their various optical/plasmonic and magnetic properties.
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42Draz, M. S.; Shafiee, H. Applications of Gold Nanoparticles in Virus Detection. Theranostics 2018, 8, 1985– 2017, DOI: 10.7150/thno.23856Google Scholar42https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXit1Srtb7O&md5=75ecce9d6b9e1b25661750fcfe1251a9Applications of gold nanoparticles in virus detectionDraz, Mohamed Shehata; Shafiee, HadiTheranostics (2018), 8 (7), 1985-2017CODEN: THERDS; ISSN:1838-7640. (Ivyspring International Publisher)A review. Viruses are the smallest known microbes, yet they cause the most significant losses in human health. Most of the time, the best-known cure for viruses is the innate immunol. defense system of the host; otherwise, the initial prevention of viral infection is the only alternative. Therefore, diagnosis is the primary strategy toward the overarching goal of virus control and elimination. The introduction of a new class of nanoscale materials with multiple unique properties and functions has sparked a series of breakthrough applications. Gold nanoparticles (AuNPs) are widely reported to guide an impressive resurgence in biomedical and diagnostic applications. Here, we the applications of AuNPs in virus testing and detection. The developed AuNP-based detection techniques are reported for various groups of clin. relevant viruses with a special focus on the applied types of bio-AuNP hybrid structures, virus detection targets, and assay modalities and formats. We pay particular attention to highlighting the functional role and activity of each core Au nanostructure and the resultant detection improvements in terms of sensitivity, detection range, and time. In addn., we provide a general summary of the contributions of AuNPs to the mainstream methods of virus detection, tech. measures, and recommendations required in guidance toward com. in-field applications.
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43Dykman, L. A.; Khlebtsov, N. G. Gold Nanoparticles in Biology and Medicine: Recent Advances and Prospects. Acta Naturae 2011, 3, 34– 55, DOI: 10.32607/20758251-2011-3-2-34-55Google Scholar43https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC38nns12htQ%253D%253D&md5=51943c1089c3d109b251a85db98a067eGold nanoparticles in biology and medicine: recent advances and prospectsDykman L A; Khlebtsov N GActa naturae (2011), 3 (2), 34-55 ISSN:2075-8251.Functionalized gold nanoparticles with controlled geometrical and optical properties are the subject of intensive studies and biomedical applications, including genomics, biosensorics, immunoassays, clinical chemistry, laser phototherapy of cancer cells and tumors, the targeted delivery of drugs, DNA and antigens, optical bioimaging and the monitoring of cells and tissues with the use of state-of-the-art detection systems. This work will provide an overview of the recent advances and current challenges facing the biomedical application of gold nanoparticles of various sizes, shapes, and structures. The review is focused on the application of gold nanoparticle conjugates in biomedical diagnostics and analytics, photothermal and photodynamic therapies, as a carrier for delivering target molecules, and on the immunological and toxicological properties. Keeping in mind the huge volume and high speed of the data update rate, 2/3 of our reference list (certainly restricted to 250 Refs.) includes publications encompassing the past 5 years.
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44Khan, M. S.; Vishakante, G. D.; Siddaramaiah, H. Gold Nanoparticles: A Paradigm Shift in Biomedical Applications. Adv. Colloid Interface Sci. 2013, 199–200, 44– 58, DOI: 10.1016/j.cis.2013.06.003Google Scholar44https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtFamurjI&md5=aeb544809e0b8a37e30744614716c72cGold nanoparticles: A paradigm shift in biomedical applicationsKhan, Mohammed S.; Vishakante, Gowda D.; Siddaramaiah HAdvances in Colloid and Interface Science (2013), 199-200 (), 44-58CODEN: ACISB9; ISSN:0001-8686. (Elsevier B.V.)A review. In the medical field, majority of the active ingredients exists in the form of solid particle (90% of all medicines). Nanotechnol. had grabbed the attention of many scientists working in different aspects and gave them a vivid imagination in order to utilize the nanotechnol. in an innovative way according to their needs. One of the major applications of nanotechnol. is drug delivery through nanoparticles which is on boom for the researchers and gives a challenging environment for the researchers. Among them upcoming challenge is the use of inorg. nanoparticles for the drug delivery and related aspects. There is growing interests in usage of inorg. nanoparticles in medicine due to their size, and unique phys. properties that make them different from other nanoparticulate systems. This review will lay special emphasis on the uniqueness of inorg. nanoparticles esp. gold nanoparticles as a drug delivery vehicle and moreover will present a wide spread scenario of gold nanoparticles that has been used for treatment of life threatening diseases like cancer.
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45Ghosh, S. K.; Pal, T. Interparticle Coupling Effect on the Surface Plasmon Resonance of Gold Nanoparticles: From Theory to Applications. Chem. Rev. 2007, 107, 4797– 4862, DOI: 10.1021/cr0680282Google Scholar45https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXht1yrt7zK&md5=9ce7a095da187d983856f61cec8e9618Interparticle Coupling Effect on the Surface Plasmon Resonance of Gold Nanoparticles: From Theory to ApplicationsGhosh, Sujit Kumar; Pal, TarasankarChemical Reviews (Washington, DC, United States) (2007), 107 (11), 4797-4862CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review. This article presents the varieties in synthetic strategies and characterization of nanoscale gold particles assembled into an aggregate structure.
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46Qiu, G.; Gai, Z.; Tao, Y.; Schmitt, J.; Kullak-Ublick, G. A.; Wang, J. Dual-Functional Plasmonic Photothermal Biosensors for Highly Accurate Severe Acute Respiratory Syndrome Coronavirus 2 Detection. ACS Nano 2020, 14, 5268– 5277, DOI: 10.1021/acsnano.0c02439Google Scholar46https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXmvVCksr8%253D&md5=49fd6f805d926ee5e95a72763d574e4cDual-Functional Plasmonic Photothermal Biosensors for Highly Accurate Severe Acute Respiratory Syndrome Coronavirus 2 DetectionQiu, Guangyu; Gai, Zhibo; Tao, Yile; Schmitt, Jean; Kullak-Ublick, Gerd A.; Wang, JingACS Nano (2020), 14 (5), 5268-5277CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)The ongoing outbreak of the novel coronavirus disease (COVID-19) has spread globally and poses a threat to public health in more than 200 countries. Reliable lab. diagnosis of the disease has been one of the foremost priorities for promoting public health interventions. The routinely used reverse transcription polymerase chain reaction (RT-PCR) is currently the ref. method for COVID-19 diagnosis. However, it also reported a no. of false-pos. or -neg. cases, esp. in the early stages of the novel virus outbreak. In this work, a dual-functional plasmonic biosensor combining the plasmonic photothermal (PPT) effect and localized surface plasmon resonance (LSPR) sensing transduction provides an alternative and promising soln. for the clin. COVID-19 diagnosis. The two-dimensional gold nanoislands (AuNIs) functionalized with complementary DNA receptors can perform a sensitive detection of the selected sequences from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through nucleic acid hybridization. For better sensing performance, the thermoplasmonic heat is generated on the same AuNIs chip when illuminated at their plasmonic resonance frequency. The localized PPT heat is capable to elevate the in situ hybridization temp. and facilitate the accurate discrimination of two similar gene sequences. Our dual-functional LSPR biosensor exhibits a high sensitivity toward the selected SARS-CoV-2 sequences with a lower detection limit down to the concn. of 0.22 pM and allows precise detection of the specific target in a multigene mixt. This study gains insight into the thermoplasmonic enhancement and its applicability in the nucleic acid tests and viral disease diagnosis.
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47Ma, C.; Li, C.; Wang, F.; Ma, N.; Li, X.; Li, Z.; Deng, Y.; Wang, Z.; Xi, Z.; Tang, Y.; He, N. Magnetic Nanoparticles-Based Extraction and Verification of Nucleic Acids from Different Sources. J. Biomed. Nanotechnol. 2013, 9, 703– 709, DOI: 10.1166/jbn.2013.1566Google Scholar47https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXltlGqsLg%253D&md5=6b92896860978ae34dde64b9789f42bdMagnetic nanoparticles-based extraction and verification of nucleic acids from different sourcesMa, Chao; Li, Chuanyan; Wang, Fang; Ma, Ningning; Li, Xiaolong; Li, Zhiyang; Deng, Yan; Wang, Zhifei; Xi, Zhijiang; Tang, Yongjun; He, NongyueJournal of Biomedical Nanotechnology (2013), 9 (4), 703-709CODEN: JBNOAB; ISSN:1550-7033. (American Scientific Publishers)In many mol. biol. and genetic technol. studies, the amt. of available DNA can be one of the important criteria for selecting the samples from different sources. Compared with those genomic DNA methods using org. solvents or other traditional com. kits, the method based on magnetic nanoparticles (MNPs) and adsorption technol. has many remarkable advantages like being time-saving and cost effective without the laborious centrifugation or pptn. steps, and more importantly it has the great potential and esp. suitable for automated DNA extn. and up-scaling. In this paper, the extn. efficiency of genomic nucleic acids based on magnetic nanoparticles from four different sources including bacteria, yeast, human blood and virus samples are compared and verified. After measurement and verification of the extd. genomic nucleic acids, it was shown that all these genomic nucleic acids extd. using the MNPs method can be of high yield and be available for next mol. biol. steps.
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48Borlido, L.; Azevedo, A. M.; Roque, A. C.; Aires-Barros, M. R. Magnetic Separations in Biotechnology. Biotechnol. Adv. 2013, 31, 1374– 1385, DOI: 10.1016/j.biotechadv.2013.05.009Google Scholar48https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtVWlsr%252FI&md5=c103af906cf437b04ce71ade5c66c223Magnetic separations in biotechnologyBorlido, L.; Azevedo, A. M.; Roque, A. C. A.; Aires-Barros, M. R.Biotechnology Advances (2013), 31 (8), 1374-1385CODEN: BIADDD; ISSN:0734-9750. (Elsevier)A review. Magnetic sepns. are probably one of the most versatile sepn. processes in biotechnol. as they are able to purify cells, viruses, proteins and nucleic acids directly from crude samples. The fast and gentle process in combination with its easy scale-up and automation provide unique advantages over other sepn. techniques. In the midst of this process are the magnetic adsorbents tailored for the envisioned target and whose complex synthesis spans over multiple fields of science. In this context, this article reviews both the synthesis and tailoring of magnetic adsorbents for biosepns. as well as their ultimate application.
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49Chen, Y. T.; Kolhatkar, A. G.; Zenasni, O.; Xu, S.; Lee, T. R. Biosensing Using Magnetic Particle Detection Techniques. Sensors 2017, 17, 2300, DOI: 10.3390/s17102300Google Scholar49https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXkt1Cns78%253D&md5=419ac0252c46f6e9e64b1dcdf00717c5Biosensing using magnetic particle detection techniquesChen, Yi-Ting; Kolhatkar, Arati G.; Zenasni, Oussama; Xu, Shoujun; Lee, T. RandallSensors (2017), 17 (10), 2300/1-2300/36CODEN: SENSC9; ISSN:1424-8220. (MDPI AG)Magnetic particles are widely used as signal labels in a variety of biol. sensing applications, such as mol. detection and related strategies that rely on ligand-receptor binding. In this review, we explore the fundamental concepts involved in designing magnetic particles for biosensing applications and the techniques used to detect them. First, we briefly describe the magnetic properties that are important for bio-sensing applications and highlight the assocd. key parameters (such as the starting materials, size, functionalization methods, and bio-conjugation strategies). Subsequently, we focus on magnetic sensing applications that utilize several types of magnetic detection techniques: spintronic sensors, NMR (NMR) sensors, superconducting quantum interference devices (SQUIDs), sensors based on the at. magnetometer (AM), and others. From the studies reported, we note that the size of the MPs is one of the most important factors in choosing a sensing technique.
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50Rocha-Santos, T. A. P. Sensors and Biosensors Based on Magnetic Nanoparticles. TrAC, Trends Anal. Chem. 2014, 62, 28– 36, DOI: 10.1016/j.trac.2014.06.016Google Scholar50https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsVWqs7zO&md5=4e017d8a8f1dd35543423e40cb49b306Sensors and biosensors based on magnetic nanoparticlesRocha-Santos, Teresa A. P.TrAC, Trends in Analytical Chemistry (2014), 62 (), 28-36CODEN: TTAEDJ; ISSN:0165-9936. (Elsevier B. V.)Magnetic nanoparticles (MNPs) have attracted a growing interest in the development and fabrication of sensors and biosensors for several applications. MNPs can be integrated into the transducer materials and/or be dispersed in the sample followed by their attraction by an external magnetic field onto the active detection surface of the (bio)sensor. This review describes and discusses the recent applications of MNPs in sensors and biosensors, taking into consideration their anal. figures of merit. This work also addresses the future trends and perspectives of sensors and biosensors based on MNPs.
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51Lee, A. H. F.; Gessert, S. F.; Chen, Y.; Sergeev, N. V.; Haghiri, B. Preparation of Iron Oxide Silica Particles for Zika Viral RNA Extraction. Heliyon 2018, 4, e00572, DOI: 10.1016/j.heliyon.2018.e00572Google ScholarThere is no corresponding record for this reference.
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52Wang, J.; Ali, Z.; Si, J.; Wang, N.; He, N.; Li, Z. Simultaneous Extraction of DNA and RNA from Hepatocellular Carcinoma (Hep G2) Based on Silica-Coated Magnetic Nanoparticles. J. Nanosci. Nanotechnol. 2017, 17, 802– 806, DOI: 10.1166/jnn.2017.12442Google Scholar52https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtVCntLrN&md5=29144f4703bd9195d147b23a1fdd252aSimultaneous extraction of DNA and RNA from hepatocellular carcinoma (Hep G2) based on silica-coated magnetic nanoparticlesWang, Jiuhai; Ali, Zeeshan; Si, Jin; Wang, Nianyue; He, Nongyue; Li, ZhiyangJournal of Nanoscience and Nanotechnology (2017), 17 (1), 802-806CODEN: JNNOAR; ISSN:1533-4880. (American Scientific Publishers)Nucleic acid (NA) extn. from cancer cells is an essential step in mol. oncol. testing. The conventional NA extn. protocols, based on several ultracentrifugation steps, suffer from time-consuming and complex manipulation. Here, a magnetic nanoparticle (MNP) based method for simultaneous extn. of DNA and RNA from cancer cells is described. This MNP based technique has received great attention and significant interest due to its convenient manipulation, low cost and ease for automation. Different factors including lysis buffer, ethanol, MNPs and washing buffers which may affect the yield of nucleic acid were optimized. The av. yield of DNA and RNA obtained from 1 mL Hep G2 (∼106 cells) ranged from 9.7 to 14.7 μg with A260/A280 values between 1.68 and 2.01. The isolated DNA and RNA, using this method, were suitable for downstream activities such as PCR and RT-PCR.
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53Zhang, H.; Xu, T.; Li, C.-W.; Yang, M. A Microfluidic Device with Microbead Array for Sensitive Virus Detection and Genotyping Using Quantum Dots as Fluorescence Labels. Biosens. Bioelectron. 2010, 25, 2402– 2407, DOI: 10.1016/j.bios.2010.02.032Google Scholar53https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXmslOjs7w%253D&md5=33d47aea793823a8ddc38db264ef8e50A microfluidic device with microbead array for sensitive virus detection and genotyping using quantum dots as fluorescence labelsZhang, He; Xu, Tao; Li, Cheuk-Wing; Yang, MengsuBiosensors & Bioelectronics (2010), 25 (11), 2402-2407CODEN: BBIOE4; ISSN:0956-5663. (Elsevier B.V.)In this study, a novel microfluidic device with microbead array was developed and sensitive genotyping of HBV was demonstrated using quantum dot as labels. This device was assembled by using two PDMS slabs featured with different microstructures and channel depths for the construction of a functional region comprising a chamber array and a single sampling microchannel. Since the chamber array and its sampling channel are of different channel depths and are bonded face-to-face, weir structures are generated to confine the microbeads which could be addressed using the microfluidic channel. Highly sensitive virus DNA detection was achieved by the enhanced mass transport in the microfluidics and the rapid reaction dynamics of suspension microbead array. The device could detect 1000 copies/mL of HBV virus in clin. serum samples using in vitro transcribed RNA as the target mols. Based on DNA hybridization with quantum dots labels, on-chip virus genotyping was also demonstrated with high discrimination specificity and sensitivity (4 pM, S/N >3) using synthesized HBV DNA probes. This microfluidic device combines the rapid binding kinetics of homogeneous assays of microbead array, the liq. handling capability of microfluidics, and the fluorescence detection sensitivity of quantum dots to provide a platform for high sensitivity virus DNA anal. with small reagent consumption, short assay time and parallel detection.
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54Wang, T.; Zheng, Z.; Zhang, X.-E.; Wang, H. Quantum Dot-Fluorescence In Situ Hybridisation for Ectromelia Virus Detection Based on Biotin–Streptavidin Interactions. Talanta 2016, 158, 179– 184, DOI: 10.1016/j.talanta.2016.04.052Google Scholar54https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XoslyktLg%253D&md5=7ead7412aa12e47ba598cb9c2be1e4e5Quantum dot-fluorescence in situ hybridization for Ectromelia virus detection based on biotin-streptavidin interactionsWang, Ting; Zheng, Zhenhua; Zhang, Xian-En; Wang, HanzhongTalanta (2016), 158 (), 179-184CODEN: TLNTA2; ISSN:0039-9140. (Elsevier B.V.)Ectromelia virus (ECTV) is an pathogen that can lead to a lethal, acute toxic disease known as mouse-pox in mice. Prevention and control of ECTV infection requires the establishment of a rapid and sensitive diagnostic system for detecting the virus. In the present study, we developed a method of quantum-dot-fluorescence based in situ hybridization for detecting ECTV genome DNA. Using biotin-dUTP to replace dTTP, biotin was incorporated into a DNA probe during polymerase chain reaction. High sensitivity and specificity of ECTV DNA detection were displayed by fluorescent quantum dots based on biotin-streptavidin interactions. ECTV DNA was then detected by streptavidin-conjugated quantum dots that bound the biotin-labeled probe. Results indicated that the established method can visualize ECTV genomic DNA in both infected cells and mouse tissues. To our knowledge, this is the first study reporting quantum-dot-fluorescence based in situ hybridization for the detection of viral nucleic acids, providing a ref. for the identification and detection of other viruses.
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55Papp, I.; Sieben, C.; Ludwig, K.; Roskamp, M.; Böttcher, C.; Schlecht, S.; Herrmann, A.; Haag, R. Inhibition of Influenza Virus Infection by Multivalent Sialic-Acid-Functionalized Gold Nanoparticles. Small 2010, 6, 2900– 2906, DOI: 10.1002/smll.201001349Google Scholar55https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhsFGgsL7F&md5=c6aa4a528310d64f87acd885e16c3692Inhibition of Influenza Virus Infection by Multivalent Sialic-Acid-Functionalized Gold NanoparticlesPapp, Ilona; Sieben, Christian; Ludwig, Kai; Roskamp, Meike; Boettcher, Christoph; Schlecht, Sabine; Herrmann, Andreas; Haag, RainerSmall (2010), 6 (24), 2900-2906CODEN: SMALBC; ISSN:1613-6810. (Wiley-VCH Verlag GmbH & Co. KGaA)An efficient synthesis of sialic-acid-terminated glycerol dendron to chem. functionalize 2 nm and 14 nm gold nanoparticles (AuNPs) is described. These nanoparticles are highly stable and show high activity towards the inhibition of influenza virus infection. As the binding of the viral fusion protein hemagglutinin to the host cell surface is mediated by sialic acid receptors, a multivalent interaction with sialic-acid-functionalized AuNPs is expected to competitively inhibit viral infection. Electron microscopy techniques and biochem. anal. show a high binding affinity of the 14 nm AuNPs to hemagglutinin on the virus surface and, less efficiently, to isolated hemagglutinin. The functionalized AuNPs are nontoxic to the cells under the conditions studied. This approach allows a new type of mol.-imaging activity-correlation and is of particular relevance for further application in alternative antiviral therapy.
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56Sametband, M.; Shukla, S.; Meningher, T.; Hirsh, S.; Mendelson, E.; Sarid, R.; Gedanken, A.; Mandelboim, M. Effective Multi-Strain Inhibition of Influenza Virus by Anionic Gold Nanoparticles. MedChemComm 2011, 2, 421– 423, DOI: 10.1039/c0md00229aGoogle Scholar56https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXls1Khtrk%253D&md5=2caa7a1ef8db801d9e31b76f9927f01aEffective multi-strain inhibition of influenza virus by anionic gold nanoparticlesSametband, Matias; Shukla, Sourabh; Meningher, Tal; Hirsh, Shira; Mendelson, Ella; Sarid, Ronit; Gedanken, Aharon; Mandelboim, MichalMedChemComm (2011), 2 (5), 421-423CODEN: MCCEAY; ISSN:2040-2503. (Royal Society of Chemistry)The fight against highly contagious influenza infection is often hampered by the appearance of drug resistant strains and the inadequacy of vaccines targeted only against specific variants. The authors report a novel route to inhibit influenza using anionic gold nanoparticles, which show effective inhibition properties against several influenza strains. The inhibition of influenza, achieved through gold nanoparticles with different anionic groups, suggested that blocking of viral attachment to cell surface could be the primary mechanism of inhibition, although viral fusion inhibition could not be excluded. At the same time, variation in the degree of inhibition with the anionic groups indicated that the antiviral activity of the nanoparticles is not merely governed by the charge d. but the functional group itself has a role to play.
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57Cagno, V.; Andreozzi, P.; D’Alicarnasso, M.; Jacob Silva, P.; Mueller, M.; Galloux, M.; Le Goffic, R.; Jones, S. T.; Vallino, M.; Hodek, J.; Weber, J.; Sen, S.; Janeček, E.-R.; Bekdemir, A.; Sanavio, B.; Martinelli, C.; Donalisio, M.; Rameix Welti, M.-A.; Eleouet, J.-F.; Han, Y.; Kaiser, L.; Vukovic, L.; Tapparel, C.; Král, P.; Krol, S.; Lembo, D.; Stellacci, F. Broad-Spectrum Non-Toxic Antiviral Nanoparticles with a Virucidal Inhibition Mechanism. Nat. Mater. 2018, 17, 195– 203, DOI: 10.1038/nmat5053Google Scholar57https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhvF2lsbzN&md5=d66943a3a85ef5f924e1dd09fc308b59Broad-spectrum non-toxic antiviral nanoparticles with a virucidal inhibition mechanismCagno, Valeria; Andreozzi, Patrizia; D'Alicarnasso, Marco; Silva, Paulo Jacob; Mueller, Marie; Galloux, Marie; Le Goffic, Ronan; Jones, Samuel T.; Vallino, Marta; Hodek, Jan; Weber, Jan; Sen, Soumyo; Janecek, Emma-Rose; Bekdemir, Ahmet; Sanavio, Barbara; Martinelli, Chiara; Donalisio, Manuela; Rameix Welti, Marie-Anne; Eleouet, Jean-Francois; Han, Yanxiao; Kaiser, Laurent; Vukovic, Lela; Tapparel, Caroline; Kral, Petr; Krol, Silke; Lembo, David; Stellacci, FrancescoNature Materials (2018), 17 (2), 195-203CODEN: NMAACR; ISSN:1476-1122. (Nature Research)Viral infections kill millions yearly. Available antiviral drugs are virus-specific and active against a limited panel of human pathogens. There are broad-spectrum substances that prevent the first step of virus-cell interaction by mimicking heparan sulfate proteoglycans (HSPG), the highly conserved target of viral attachment ligands (VALs). The reversible binding mechanism prevents their use as a drug, because, upon diln., the inhibition is lost. Known VALs are made of closely packed repeating units, but the aforementioned substances are able to bind only a few of them. We designed antiviral nanoparticles with long and flexible linkers mimicking HSPG, allowing for effective viral assocn. with a binding that we simulate to be strong and multivalent to the VAL repeating units, generating forces (∼190 pN) that eventually lead to irreversible viral deformation. Virucidal assays, electron microscopy images, and mol. dynamics simulations support the proposed mechanism. These particles show no cytotoxicity, and in vitro nanomolar irreversible activity against herpes simplex virus (HSV), human papilloma virus, respiratory syncytial virus (RSV), dengue and lenti virus. They are active ex vivo in human cervicovaginal histocultures infected by HSV-2 and in vivo in mice infected with RSV.
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58Kim, J.; Yeom, M.; Lee, T.; Kim, H.-O.; Na, W.; Kang, A.; Lim, J.-W.; Park, G.; Park, C.; Song, D.; Haam, S. Porous Gold Nanoparticles for Attenuating Infectivity of Influenza a Virus. J. Nanobiotechnol. 2020, 18, 54, DOI: 10.1186/s12951-020-00611-8Google Scholar58https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXlvFGhu7c%253D&md5=8ecafadf59d12e990f4090ba2f87820bPorous gold nanoparticles for attenuating infectivity of influenza A virusKim, Jinyoung; Yeom, Minjoo; Lee, Taeksu; Kim, Hyun-Ouk; Na, Woonsung; Kang, Aram; Lim, Jong-Woo; Park, Geunseon; Park, Chaewon; Song, Daesub; Haam, SeungjooJournal of Nanobiotechnology (2020), 18 (1), 54CODEN: JNOAAO; ISSN:1477-3155. (BioMed Central Ltd.)Abstr.: Background: Influenza viruses (IVs) have become increasingly resistant to antiviral drugs that target neuraminidase and matrix protein 2 due to gene mutations that alter their drug-binding target protein regions. Consequently, almost all recent IV pandemics have exhibited resistance to com. antiviral vaccines. To overcome this challenge, an antiviral target is needed that is effective regardless of genetic mutations. Main body: In particular, hemagglutinin (HA), a highly conserved surface protein across many IV strains, could be an effective antiviral target as it mediates binding of IVs with host cell receptors, which is crucial for membrane fusion. HA has 6 disulfide bonds that can easily bind with the surfaces of gold nanoparticles. Herein, we fabricated porous gold nanoparticles (PoGNPs) via a surfactant-free emulsion method that exhibited strong affinity for disulfide bonds due to gold-thiol interactions, and provided extensive surface area for these interactions. A remarkable decrease in viral infectivity was demonstrated by increased cell viability results after exposing MDCK cells to various IV strains (H1N1, H3N2, and H9N2) treated with PoGNP. Most of all, the viability of MDCK cells infected with all IV strains increased to 96.8% after PoGNP treatment of the viruses compared to 33.9% cell viability with non-treated viruses. Intracellular viral RNA quantification by real-time RT-PCR also confirmed that PoGNP successfully inhibited viral membrane fusion by blocking the viral entry process through conformational deformation of HA. Conclusion: We believe that the technique described herein can be further developed for PoGNP-utilized antiviral protection as well as metal nanoparticle-based therapy to treat viral infection. Addnl., facile detection of IAV can be achieved by developing PoGNP as a multiplatform for detection of the virus.
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59Huang, X.; Li, M.; Xu, Y.; Zhang, J.; Meng, X.; An, X.; Sun, L.; Guo, L.; Shan, X.; Ge, J.; Chen, J.; Luo, Y.; Wu, H.; Zhang, Y.; Jiang, Q.; Ning, X. Novel Gold Nanorod-Based HR1 Peptide Inhibitor for Middle East Respiratory Syndrome Coronavirus. ACS Appl. Mater. Interfaces 2019, 11, 19799– 19807, DOI: 10.1021/acsami.9b04240Google Scholar59https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXpvVClsro%253D&md5=59aff1b3a8c12706e2f45245c23f59deNovel Gold Nanorod-Based HR1 Peptide Inhibitor for Middle East Respiratory Syndrome CoronavirusHuang, Xinyu; Li, Meng; Xu, Yurui; Zhang, Jikang; Meng, Xia; An, Xueying; Sun, Lei; Guo, Leilei; Shan, Xue; Ge, Junliang; Chen, Jiao; Luo, Yadong; Wu, Heming; Zhang, Yu; Jiang, Qing; Ning, XinghaiACS Applied Materials & Interfaces (2019), 11 (22), 19799-19807CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Middle East respiratory syndrome coronavirus (MERS-CoV) causes a severe acute respiratory syndrome-like illness with high pathogenicity and mortality due to the lack of effective therapeutics. Currently, only few antiviral agents are available for the treatment of MERS, but their effects have been greatly impaired by low antiviral activity, poor metabolic stability, and serious adverse effects. Therefore, the development of effective treatment for MERS is urgently needed. In this study, a series of heptad repeat 1 (HR1) peptide inhibitors have been developed to inhibit HR1/HR2-mediated membrane fusion between MERS-CoV and host cells, which is the major pathway of MERS-CoV-induced host infections. Particularly, peptide pregnancy-induced hypertension (PIH) exhibits potent inhibitory activity with IC50 of 1.171 μM, and its inhibitory effects can be further increased to 10-fold by forming a gold nanorod complex (PIH-AuNRs). In addn., PIH-AuNRs display enhanced metabolic stability and biocompatibility in vitro and in vivo and, therefore, effectively prevent MERS-CoV-assocd. membrane fusion. In summary, PIH-AuNRs represent a novel class of antiviral agents and have a great potential in treating MERS in the clinic.
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60Yang, X. X.; Li, C. M.; Huang, C. Z. Curcumin Modified Silver Nanoparticles for Highly Efficient Inhibition of Respiratory Syncytial Virus Infection. Nanoscale 2016, 8, 3040– 3048, DOI: 10.1039/C5NR07918GGoogle Scholar60https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XislKnsw%253D%253D&md5=8a288a70879432df568881c84b1d6046Curcumin modified silver nanoparticles for highly efficient inhibition of respiratory syncytial virus infectionYang, Xiao Xi; Li, Chun Mei; Huang, Cheng ZhiNanoscale (2016), 8 (5), 3040-3048CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)Interactions between nanoparticles and viruses have attracted increasing attention due to the antiviral activity of nanoparticles and the resulting possibility to be employed as biomedical interventions. In this contribution, we developed a very simple route to prep. uniform and stable silver nanoparticles (AgNPs) with antiviral properties by using curcumin, which is a member of the ginger family isolated from rhizomes of the perennial herb Curcuma longa and has a wide range of biol. activities like antioxidant, antifungal, antibacterial and anti-inflammatory effects, and acts as reducing and capping agents in this synthetic route. The tissue culture infectious dose (TCID50) assay showed that the curcumin modified silver nanoparticles (cAgNPs) have a highly efficient inhibition effect against respiratory syncytial virus (RSV) infection, giving a decrease of viral titers about two orders of magnitude at the concn. of cAgNPs under which no toxicity was found to the host cells. Mechanism investigations showed that cAgNPs could prevent RSV from infecting the host cells by inactivating the virus directly, indicating that cAgNPs are a novel promising efficient virucide for RSV.
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61Chen, Y.-N.; Hsueh, Y.-H.; Hsieh, C.- T.; Tzou, D.-Y.; Chang, P.-L. Antiviral Activity of Graphene–Silver Nanocomposites against Non-Enveloped and Enveloped Viruses. Int. J. Environ. Res. Public Health 2016, 13, 430, DOI: 10.3390/ijerph13040430Google Scholar61https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXivVWhs7Y%253D&md5=3a1be06dc09934ca4a8593d834e5bf57Antiviral activity of graphene-silver nanocomposites against non-enveloped and enveloped virusesChen, Yi-Ning; Hsueh, Yi-Huang; Hsieh, Chien-Te; Tzou, Dong-Ying; Chang, Pai-LingInternational Journal of Environmental Research and Public Health (2016), 13 (4), 430/1-430/12CODEN: IJERGQ; ISSN:1660-4601. (MDPI AG)The discovery of novel antiviral materials is important because many infectious diseases are caused by viruses. Silver nanoparticles have demonstrated strong antiviral activity, and graphene is a potential antimicrobial material due to its large surface area, high carrier mobility, and biocompatibility. No studies on the antiviral activity of nanomaterials on non-enveloped viruses have been reported. To investigate the antiviral activity of graphene oxide (GO) sheets and GO sheets with silver particles (GO-Ag) against enveloped and non-enveloped viruses, feline coronavirus (FCoV) with an envelope and infectious bursal disease virus (IBDV) without an envelope were chosen. The morphol. and sizes of GO and GO-Ag were characterized by transmission, SEM, and X-ray diffraction. A virus inhibition assay was used to identify the antiviral activity of GO and GO-Ag. Go-Ag inhibited 25% of infection by FCoV and 23% by IBDV, whereas GO only inhibited 16% of infection by FCoV but showed no antiviral activity against the infection by IBDV. Further application of GO and GO-Ag can be considered for personal protection equipment to decrease the transmission of viruses.
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62Lv, X.; Wang, P.; Bai, R.; Cong, Y.; Suo, S.; Ren, X.; Chen, C. Inhibitory Effect of Silver Nanomaterials on Transmissible Virus-Induced Host Cell Infections. Biomaterials 2014, 35, 4195– 4203, DOI: 10.1016/j.biomaterials.2014.01.054Google Scholar62https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXitFOqt7s%253D&md5=4c8e2c3bc5e136c8cacd397da707e900Inhibitory effect of silver nanomaterials on transmissible virus-induced host cell infectionsLv, Xiaonan; Wang, Peng; Bai, Ru; Cong, Yingying; Suo, Siqingaowa; Ren, Xiaofeng; Chen, ChunyingBiomaterials (2014), 35 (13), 4195-4203CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)Coronaviruses belong to the family Coronaviridae, which primarily cause infection of the upper respiratory and gastrointestinal tract of hosts. Transmissible gastroenteritis virus (TGEV) is an economically significant coronavirus that can cause severe diarrhea in pigs. Silver nanomaterials (Ag NMs) have attracted great interests in recent years due to their excellent anti-microorganism properties. Herein, four representative Ag NMs including spherical Ag nanoparticles (Ag NPs, NM-300), two kinds of silver nanowires (XFJ011) and silver colloids (XFJ04) were selected to study their inhibitory effect on TGEV-induced host cell infection in vitro. Ag NPs were uniformly distributed, with particle sizes less than 20 nm by characterization of environmental scanning electron microscope and transmission electron microscope. Two types of silver nanowires were 60 nm and 400 nm in diam., resp. The av. diam. of the silver colloids was approx. 10 nm. TGEV infection induced the occurring of apoptosis in swine testicle (ST) cells, down-regulated the expression of Bcl-2, up-regulated the expression of Bax, altered mitochondrial membrane potential, activated p38 MAPK signal pathway, and increased expression of p53 as evidenced by immunofluorescence assays, real-time PCR, flow cytometry and Western blot. Under non-toxic concns., Ag NPs and silver nanowires significantly diminished the infectivity of TGEV in ST cells. Moreover, further results showed that Ag NPs and silver nanowires decreased the no. of apoptotic cells induced by TGEV through regulating p38/mitochondria-caspase-3 signaling pathway. Our data indicate that Ag NMs are effective in prevention of TGEV-mediated cell infection as a virucidal agent or as an inhibitor of viral entry and the present findings may provide new insights into antiviral therapy of coronaviruses.
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63Li, Y.; Lin, Z.; Zhao, M.; Xu, T.; Wang, C.; Hua, L.; Wang, H.; Xia, H.; Zhu, B. Silver Nanoparticle Based Codelivery of Oseltamivir to Inhibit the Activity of the H1N1 Influenza Virus through ROS-Mediated Signaling Pathways. ACS Appl. Mater. Interfaces 2016, 8, 24385– 24393, DOI: 10.1021/acsami.6b06613Google Scholar63https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhsVCmsb7O&md5=83513b12fe12d52dcf72a9129e8f9dc0Silver Nanoparticle Based Codelivery of Oseltamivir to Inhibit the Activity of the H1N1 Influenza Virus through ROS-Mediated Signaling PathwaysLi, Yinghua; Lin, Zhengfang; Zhao, Mingqi; Xu, Tiantian; Wang, Changbing; Hua, Liang; Wang, Hanzhong; Xia, Huimin; Zhu, BingACS Applied Materials & Interfaces (2016), 8 (37), 24385-24393CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)As the therapeutic agent for antiviral applications, the clin. use of oseltamivir is limited with the appearance of drug-resistant viruses. It is important to explore novel anti-influenza drugs. The antiviral activity of silver nanoparticles (AgNPs) has attracted increasing attention in recent years and was a possibility to be employed as a biomedical intervention. Herein, we describe the synthesis of surface decoration of AgNPs by using oseltamivir (OTV) with antiviral properties and inhibition of drug resistance. Compared to silver and oseltamivir, oseltamivir-modified AgNPs (Ag@OTV) have remarkable inhibition against H1N1 infection, and less toxicity was found for MDCK cells by controlled-potential electrolysis (CPE), MTT, and transmission electron microscopy (TEM). Furthermore, Ag@OTV inhibited the activity of neuraminidase (NA) and hemagglutinin (HA) and then prevented the attachment of the H1N1 influenza virus to host cells. The investigations of the mechanism revealed that Ag@OTV could block H1N1 from infecting MDCK cells and prevent DNA fragmentation, chromatin condensation, and the activity of caspase-3. Ag@OTV remarkably inhibited the accumulation of reactive oxygen species (ROS) by the H1N1 virus and activation of AKT and p53 phosphorylation. Silver nanoparticle based codelivery of oseltamivir inhibits the activity of the H1N1 influenza virus through ROS-mediated signaling pathways. These findings demonstrate that Ag@OTV is a novel promising efficient virucide for H1N1.
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64Lin, Z.; Li, Y.; Guo, M.; Xu, T.; Wang, C.; Zhao, M.; Wang, H.; Chen, T.; Zhu, B. The Inhibition of H1N1 Influenza Virus-Induced Apoptosis by Silver Nanoparticles Functionalized with Zanamivir. RSC Adv. 2017, 7, 742– 750, DOI: 10.1039/C6RA25010FGoogle Scholar64https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtFGqtQ%253D%253D&md5=ebe5676ff40cc5fd2b1affb532bc0461The inhibition of H1N1 influenza virus-induced apoptosis by silver nanoparticles functionalized with zanamivirLin, Zhengfang; Li, Yinghua; Guo, Min; Xu, Tiantian; Wang, Changbing; Zhao, Mingqi; Wang, Hanzhong; Chen, Tianfeng; Zhu, BingRSC Advances (2017), 7 (2), 742-750CODEN: RSCACL; ISSN:2046-2069. (Royal Society of Chemistry)As one of the most effective drugs for influenza virus infection, clin. application of zanamivir is restricted with the emergence of resistant influenza virus. It is crucial to manuf. novel pharmaceuticals against influenza virus infection. In recent years silver nanoparticles (AgNPs) have attracted wide attention in the antiviral field. In this study, we demonstrated surface decoration of AgNPs using zanamivir (ZNV) with antiviral properties. AgNPs co-delivery of the zanamivir nanosystem was designed to reverse influenza virus resistance. In brief, zanamivir modified AgNPs (Ag@ZNV) inhibited the neuraminidase activity of the H1N1 virus. Moreover, cytopathic effect showed that Ag@ZNV remarkably resisted H1N1 virus-induced apoptosis of MDCK cells, involving DNA fragmentation, chromatin condensation and caspase-3 activation. Ag@ZNV effectively reduced the accumulation of reactive oxygen species (ROS) induced by H1N1 virus and activation of both p38 and p53 signaling pathways. Taken together, our study indicates that Ag@ZNV is a novel promising pharmaceutical against H1N1 influenza virus infection.
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65Morris, D.; Ansar, M.; Speshock, J.; Ivanciuc, T.; Qu, Y.; Casola, A.; Garofalo, R. Antiviral and Immunomodulatory Activity of Silver Nanoparticles in Experimental RSV Infection. Viruses 2019, 11, 732, DOI: 10.3390/v11080732Google Scholar65https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXisVOgu7bO&md5=a86c312d757577abef2166f0ec25d98eAntiviral and immunomodulatory activity of silver nanoparticles in experimental RSV infectionMorris, Dorothea; Ansar, Maria; Speshock, Janice; Ivanciuc, Teodora; Qu, Yue; Casola, Antonella; Garofalo, Roberto P.Viruses (2019), 11 (8), 732CODEN: VIRUBR; ISSN:1999-4915. (MDPI AG)Wild birds play an important role as reservoir hosts and vectors for zoonotic arboviruses and foster their spread. Usutu virus (USUV) has been circulating endemically in Germany since 2011, while West Nile virus (WNV) was first diagnosed in several bird species and horses in 2018. In 2017 and 2018, we screened 1709 live wild and zoo birds with real-time polymerase chain reaction and serol. assays. Moreover, organ samples from bird carcasses submitted in 2017 were investigated. Overall, 57 blood samples of the live birds (2017 and 2018), and 100 organ samples of dead birds (2017) were pos. for USUV-RNA, while no WNV-RNA-pos. sample was found. Phylogenetic anal. revealed the first detection of USUV lineage Europe 2 in Germany and the spread of USUV lineages Europe 3 and Africa 3 towards Northern Germany. USUV antibody prevalence rates were high in Eastern Germany in both years. On the contrary, in Northern Germany, high seroprevalence rates were first detected in 2018, with the first emergence of USUV in this region. Interestingly, high WNV-specific neutralizing antibody titers were obsd. in resident and short-distance migratory birds in Eastern Germany in 2018, indicating the first signs of a local WNV circulation.
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66Osminkina, L. A.; Timoshenko, V. Y.; Shilovsky, I. P.; Kornilaeva, G. V.; Shevchenko, S. N.; Gongalsky, M. B.; Tamarov, K. P.; Abramchuk, S. S.; Nikiforov, V. N.; Khaitov, M. R.; Karamov, E. V. Porous Silicon Nanoparticles as Scavengers of Hazardous Viruses. J. Nanopart. Res. 2014, 16, 2430, DOI: 10.1007/s11051-014-2430-2Google ScholarThere is no corresponding record for this reference.
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67Lin, Z.; Li, Y.; Guo, M.; Xiao, M.; Wang, C.; Zhao, M.; Xu, T.; Xia, Y.; Zhu, B. Inhibition of H1N1 Influenza Virus by Selenium Nanoparticles Loaded with Zanamivir through P38 and Jnk Signaling Pathways. RSC Adv. 2017, 7, 35290– 35296, DOI: 10.1039/C7RA06477BGoogle Scholar67https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtFOlsLfL&md5=00f058686a48fa9dcc1271b7f477cfb7Inhibition of H1N1 influenza virus by selenium nanoparticles loaded with zanamivir through p38 and JNK signaling pathwaysLin, Zhengfang; Li, Yinghua; Guo, Min; Xiao, Misi; Wang, Changbing; Zhao, Mingqi; Xu, Tiantian; Xia, Yu; Zhu, BingRSC Advances (2017), 7 (56), 35290-35296CODEN: RSCACL; ISSN:2046-2069. (Royal Society of Chemistry)Zanamivir is an effective drug for influenza virus infection, but strong mol. polarity and aq. soly. limit its clin. application. In recent years, selenium nanoparticles (SeNPs) have attracted attention in the biol. field. In this study, surface decoration of SeNPs using zanamivir (ZNV) with antiviral properties was demonstrated. SeNPs co-delivery of a zanamivir nanosystem was designed to reverse influenza virus infection. In breif, the MTT assay, cytopathic effect and nucleic acid level of the virus suggested that zanamivir modified SeNPs (Se@ZNV) resisted proliferation of H1N1 virus and MDCK cells achieved higher viability after treatment with this compd. Besides, both activation and expression of caspase-3 induced during H1N1 virus infection were depressed when treated with Se@ZNV. Furthermore, phosphorylation of p38 and JNK were down-regulated by Se@ZNV. Taken together, our study indicates that Se@ZNV is a novel promising pharmaceutical against H1N1 influenza virus infection.
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68Li, Y.; Lin, Z.; Guo, M.; Zhao, M.; Xia, Y.; Wang, C.; Xu, T.; Zhu, B. Inhibition of H1N1 Influenza Virus-Induced Apoptosis by Functionalized Selenium Nanoparticles with Amantadine through ROS-Mediated AKT Signaling Pathways. Int. J. Nanomed. 2018, 13, 2005– 2016, DOI: 10.2147/IJN.S155994Google Scholar68https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXit1GltbrK&md5=43468dbd3ff9129de5293748586e6a67Inhibition of H1N1 influenza virus-induced apoptosis by functionalized selenium nanoparticles with amantadine through ROS-mediated AKT signaling pathwaysLi, Yinghua; Lin, Zhengfang; Guo, Min; Zhao, Mingqi; Xia, Yu; Wang, Changbing; Xu, TiantianInternational Journal of Nanomedicine (2018), 13 (), 2005-2016CODEN: IJNNHQ; ISSN:1178-2013. (Dove Medical Press Ltd.)Introduction: As a therapeutic antiviral agent, the clin. application of amantadine (AM) is limited by the emergence of drug-resistant viruses. To overcome the drug-resistant viruses and meet the growing demand of clin. diagnosis, the use of biol. nanoparticles (NPs) has increased in order to develop novel anti-influenza drugs. The antiviral activity of selenium NPs with low toxicity and excellent activities has attracted increasing attention for biomedical intervention in recent years. Methods and results: In the present study, surface decoration of selenium NPs by AM (Se@AM) was designed to reverse drug resistance caused by influenza virus infection. Se@AM with less toxicity remarkably inhibited the ability of H1N1 influenza to infect host cells through suppression of the neuraminidase activity. Moreover, Se@AM could prevent H1N1 from infecting Madin Darby Canine Kidney cell line and causing cell apoptosis supported by DNA fragmentation and chromatin condensation. Furthermore, Se@AM obviously inhibited the generation of reactive oxygen species and activation of phosphorylation of AKT. Conclusion: These results demonstrate that Se@AM is a potentially efficient antiviral pharmaceutical agent for H1N1 influenza virus.
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69Lin, Z.; Li, Y.; Gong, G.; Xia, Y.; Wang, C.; Chen, Y.; Hua, L.; Zhong, J.; Tang, Y.; Liu, X.; Zhu, B. Restriction of H1N1 Influenza Virus Infection by Selenium Nanoparticles Loaded with Ribavirin Via Resisting Caspase-3 Apoptotic Pathway. Int. J. Nanomed. 2018, 13, 5787– 5797, DOI: 10.2147/IJN.S177658Google Scholar69https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtVems73E&md5=9ab999fccdfe182db4118c262583b0a4Restriction of H1N1 influenza virus infection by selenium nanoparticles loaded with ribavirin via resisting caspase-3 apoptotic pathwayLin, Zhengfang; Li, Yinghua; Gong, Guifang; Xia, Yu; Wang, Changbing; Chen, Yi; Hua, Liang; Zhong, Jiayu; Tang, Ying; Liu, Xiaomin; Zhu, BingInternational Journal of Nanomedicine (2018), 13 (), 5787-5797CODEN: IJNNHQ; ISSN:1178-2013. (Dove Medical Press Ltd.)Ribavirin (RBV) is a broad-spectrum antiviral drug. Selenium nanoparticles (SeNPs) attract much attention in the biomedical field and are used as carriers of drugs in current research studies. In this study, SeNPs were decorated by RBV, and the novel nanoparticle system was well characterized. Madin-Darby Canine Kidney cells were infected with H1N1 influenza virus before treatment with RBV, SeNPs, and SeNPs loaded with RBV (Se@RBV). MTT assay showed that Se@RBV nanoparticles protect cells during H1N1 infection in vitro. Se@RBV depressed virus titer in the culture supernatant. Intracellular localization detection revealed that Se@RBV accumulated in lysosome and escaped to cytoplasm as time elapsed. Furthermore, activation of caspase-3 was resisted by Se@RBV. Expressions of proteins related to caspase-3, including cleaved poly-ADP-ribose polymerase, caspase-8, and Bax, were downregulated evidently after treatment with Se@RBV compared with the untreated infection group. In addn., phosphorylations of phosphorylated 38 (p38), JNK, and phosphorylated 53 (p53) were inhibited as well. In vivo expts. indicated that Se@RBV was found to prevent lung injury in H1N1-infected mice through hematoxylin and eosin staining. Tunel test of lung tissues present that DNA damage reached a high level but reduced substantially when treated with Se@RBV. Immunohistochem. test revealed an identical result with the in vitro expt. that activations of caspase-3 and proteins on the apoptosis pathway were restrained by Se@RBV treatment. Taken together, this study elaborates that Se@RBV is a novel promising agent against H1N1 influenza virus infection.
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70Li, Y.; Lin, Z.; Guo, M.; Xia, Y.; Zhao, M.; Wang, C.; Xu, T.; Chen, T.; Zhu, B. Inhibitory Activity of Selenium Nanoparticles Functionalized with Oseltamivir on H1N1 Influenza Virus. Int. J. Nanomed. 2017, 12, 5733– 5743, DOI: 10.2147/IJN.S140939Google Scholar70https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXitV2gtrzL&md5=cf69da91ddf57bcaedcf1139179f7f54Inhibitory activity of selenium nanoparticles functionalized with oseltamivir on H1N1 influenza virusLi, Yinghua; Lin, Zhengfang; Guo, Min; Xia, Yu; Zhao, Mingqi; Wang, Changbing; Xu, Tiantian; Chen, Tianfeng; Zhu, BingInternational Journal of Nanomedicine (2017), 12 (), 5733-5743CODEN: IJNNHQ; ISSN:1178-2013. (Dove Medical Press Ltd.)As an effective antiviral agent, the clin. application of oseltamivir (OTV) is limited by the appearance of drug-resistant viruses. Due to their low toxicity and excellent activity, the antiviral capabilities of selenium nanoparticles (SeNPs) has attracted increasing attention in recent years. To overcome the limitation of drug resistance, the use of modified NPs with biologics to explore novel anti-influenza drugs is developing rapidly. In this study, OTV surface-modified SeNPs with superior antiviral properties and restriction on drug resistance were synthesized. OTV decoration of SeNPs (Se@OTV) obviously inhibited H1N1 infection and had less toxicity. Se@OTV interfered with the H1N1 influenza virus to host cells through inhibiting the activity of hemagglutinin and neuraminidase. The mechanism was that Se@OTV was able to prevent H1N1 from infecting MDCK cells and block chromatin condensation and DNA fragmentation. Furthermore, Se@OTV inhibited the generation of reactive oxygen species and activation of p53 phosphorylation and Akt. These results demonstrate that Se@OTV is a promising efficient antiviral pharmaceutical for H1N1.
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71Ghaffari, H.; Tavakoli, A.; Moradi, A.; Tabarraei, A.; Bokharaei-Salim, F.; Zahmatkeshan, M.; Farahmand, M.; Javanmard, D.; Kiani, S. J.; Esghaei, M.; Pirhajati-Mahabadi, V.; Monavari, S. H.; Ataei-Pirkooh, A. Inhibition of H1N1 Influenza Virus Infection by Zinc Oxide Nanoparticles: Another Emerging Application of Nanomedicine. J. Biomed. Sci. 2019, 26, 70, DOI: 10.1186/s12929-019-0563-4Google Scholar71https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3Mrmslemsg%253D%253D&md5=84b81c1eb7a85ec581774b9c524767f1Inhibition of H1N1 influenza virus infection by zinc oxide nanoparticles: another emerging application of nanomedicineGhaffari Hadi; Tavakoli Ahmad; Bokharaei-Salim Farah; Javanmard Davod; Kiani Seyed Jalal; Esghaei Maryam; Monavari Seyed Hamidreza; Ataei-Pirkooh Angila; Moradi Abdolvahab; Tabarraei Alijan; Zahmatkeshan Masoumeh; Pirhajati-Mahabadi Vahid; Zahmatkeshan Masoumeh; Farahmand Mohammad; Pirhajati-Mahabadi VahidJournal of biomedical science (2019), 26 (1), 70 ISSN:.BACKGROUND: Currently available anti-influenza drugs are often associated with limitations such as toxicity and the appearance of drug-resistant strains. Therefore, there is a pressing need for the development of novel, safe and more efficient antiviral agents. In this study, we evaluated the antiviral activity of zinc oxide nanoparticles (ZnO-NPs) and PEGylated zinc oxide nanoparticles against H1N1 influenza virus. METHODS: The nanoparticles were characterized using the inductively coupled plasma mass spectrometry, x-ray diffraction analysis, and electron microscopy. MTT assay was applied to assess the cytotoxicity of the nanoparticles, and anti-influenza activity was determined by TCID50 and quantitative Real-Time PCR assays. To study the inhibitory impact of nanoparticles on the expression of viral antigens, an indirect immunofluorescence assay was also performed. RESULTS: Post-exposure of influenza virus with PEGylated ZnO-NPs and bare ZnO-NPs at the highest non-toxic concentrations could be led to 2.8 and 1.2 log10 TCID50 reduction in virus titer when compared to the virus control, respectively (P < 0.0001). At the highest non-toxic concentrations, the PEGylated and unPEGylated ZnO-NPs led to inhibition rates of 94.6 and 52.2%, respectively, which were calculated based on the viral loads. There was a substantial decrease in fluorescence emission intensity in viral-infected cell treated with PEGylated ZnO-NPs compared to the positive control. CONCLUSIONS: Taken together, our study indicated that PEGylated ZnO-NPs could be a novel, effective, and promising antiviral agent against H1N1 influenza virus infection, and future studies can be designed to explore the exact antiviral mechanism of these nanoparticles.
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72De Souza e Silva, J. M.; Hanchuk, T. D. M.; Santos, M. I.; Kobarg, J.; Bajgelman, M. C.; Cardoso, M. B. Viral Inhibition Mechanism Mediated by Surface-Modified Silica Nanoparticles. ACS Appl. Mater. Interfaces 2016, 8, 16564– 16572, DOI: 10.1021/acsami.6b03342Google Scholar72https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2s%252FosFKgtA%253D%253D&md5=86f7653675a75531f2f1445363822261Viral Inhibition Mechanism Mediated by Surface-Modified Silica Nanoparticlesde Souza E Silva Juliana Martins; Santos Murilo Izidoro; Cardoso Mateus Borba; de Souza E Silva Juliana Martins; Hanchuk Talita Diniz Melo; Kobarg Jorg; Bajgelman Marcio Chaim; Hanchuk Talita Diniz Melo; Kobarg JorgACS applied materials & interfaces (2016), 8 (26), 16564-72 ISSN:.Vaccines and therapies are not available for several diseases caused by viruses, thus viral infections result in morbidity and mortality of millions of people every year. Nanoparticles are considered to be potentially effective in inhibiting viral infections. However, critical issues related to their use include their toxicity and their mechanisms of antiviral action, which are not yet completely elucidated. To tackle these problems, we synthesized silica nanoparticles with distinct surface properties and evaluated their biocompatibility and antiviral efficacy. We show that nanoparticles exhibited no significant toxicity to mammalian cells, while declines up to 50% in the viral transduction ability of two distinct recombinant viruses were observed. We designed experiments to address the mechanism of antiviral action of our nanoparticles and found that their hydrophobic/hydrophilic characters play a crucial role. Our results reveal that the use of functionalized silica particles is a promising approach for controlling viral infection and offer promising strategies for viral control.
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73Bromberg, L.; Bromberg, D. J.; Hatton, T. A.; Bandín, I.; Concheiro, A.; Alvarez-Lorenzo, C. Antiviral Properties of Polymeric Aziridine- and Biguanide-Modified Core–Shell Magnetic Nanoparticles. Langmuir 2012, 28, 4548– 4558, DOI: 10.1021/la205127xGoogle Scholar73https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhvFahu7g%253D&md5=92c1bdcfdf990cb72de6860dbf4b6cbcAntiviral Properties of Polymeric Aziridine- and Biguanide-Modified Core-Shell Magnetic NanoparticlesBromberg, Lev; Bromberg, Daniel J.; Hatton, T. Alan; Bandin, Isabel; Concheiro, Angel; Alvarez-Lorenzo, CarmenLangmuir (2012), 28 (9), 4548-4558CODEN: LANGD5; ISSN:0743-7463. (American Chemical Society)Polycationic superparamagnetic nanoparticles (∼150-250 nm) were evaluated as virucidal agents. The particles possess a core-shell structure, with cores consisting of magnetite clusters and shells of functional silica covalently bound to poly(hexamethylene biguanide) (PHMBG), polyethyleneimine (PEI), or PEI terminated with aziridine moieties. Aziridine was conjugated to the PEI shell through cationic ring-opening polymn. The nanometric core-shell particles functionalized with biguanide or aziridine moieties are able to bind and inactivate bacteriophage MS2, herpes simplex virus HSV-1, nonenveloped infectious pancreatic necrosis virus (IPNV), and enveloped viral hemorrhagic septicemia virus (VHSV). The virus-particle complexes can be efficiently removed from the aq. milieu by simple magnetocollection.
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74Du, T.; Liang, J.; Dong, N.; Lu, J.; Fu, Y.; Fang, L.; Xiao, S.; Han, H. Glutathione-Capped Ag2S Nanoclusters Inhibit Coronavirus Proliferation through Blockage of Viral RNA Synthesis and Budding. ACS Appl. Mater. Interfaces 2018, 10, 4369– 4378, DOI: 10.1021/acsami.7b13811Google Scholar74https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhtVaqsr0%253D&md5=b1f91d4da40a3d3dcd74cf16d47d9bb1Glutathione-Capped Ag2S Nanoclusters Inhibit Coronavirus Proliferation through Blockage of Viral RNA Synthesis and BuddingDu, Ting; Liang, Jiangong; Dong, Nan; Lu, Jian; Fu, Yiying; Fang, Liurong; Xiao, Shaobo; Han, HeyouACS Applied Materials & Interfaces (2018), 10 (5), 4369-4378CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Development of novel antiviral reagents is of great importance for the control of virus spread. Here, Ag2S nanoclusters (NCs) were proved for the first time to possess highly efficient antiviral activity by using porcine epidemic diarrhea virus (PEDV) as a model of coronavirus. Analyses of virus titers showed that Ag2S NCs significantly suppressed the infection of PEDV by about 3 orders of magnitude at the noncytotoxic concn. at 12 h postinfection, which was further confirmed by the expression of viral proteins. Mechanism investigations indicated that Ag2S NCs treatment inhibits the synthesis of viral neg.-strand RNA and viral budding. Ag2S NCs treatment was also found to pos. regulate the generation of IFN-stimulating genes (ISGs) and the expression of proinflammation cytokines, which might prevent PEDV infection. This study suggest the novel underlying of Ag2S NCs as a promising therapeutic drug for coronavirus.
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75Łoczechin, A.; Séron, K.; Barras, A.; Giovanelli, E.; Belouzard, S.; Chen, Y.-T.; Metzler-Nolte, N.; Boukherroub, R.; Dubuisson, J.; Szunerits, S. Functional Carbon Quantum Dots as Medical Countermeasures to Human Coronavirus. ACS Appl. Mater. Interfaces 2019, 11, 42964– 42974, DOI: 10.1021/acsami.9b15032Google Scholar75https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhvF2ktbvL&md5=fd3d64b54ff8f279bf87bb928983e07eFunctional Carbon Quantum Dots as Medical Countermeasures to Human CoronavirusLoczechin, Aleksandra; Seron, Karin; Barras, Alexandre; Giovanelli, Emerson; Belouzard, Sandrine; Chen, Yen-Ting; Metzler-Nolte, Nils; Boukherroub, Rabah; Dubuisson, Jean; Szunerits, SabineACS Applied Materials & Interfaces (2019), 11 (46), 42964-42974CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Therapeutic options for the highly pathogenic human coronavirus (HCoV) infections are urgently needed. Anti-coronavirus therapy is however challenging, as coronaviruses are biol. diverse and rapidly mutating. The antiviral activity of seven different carbon quantum dots (CQDs) for the treatment of human coronavirus HCoV-229E infections was studied. The first generation of antiviral CQDs was derived by hydrothermal carbonization from ethylenediamine/citric acid as carbon precursors and post-modified with boronic acid ligands. These nanostructures showed a concn. dependent virus inactivation with an estd. EC50 of 52 ± 8μg mL-1. CQDs derived from 4-aminophenylboronic acid without any further modification resulted in the second-generation of anti-HCoV nanomaterials with an EC50 lowered to 5.2 ± 0.7μg mL-1. The underlying mechanism of action of these CQDs revealed to be inhibition of HCoV-229E entry that could be due to interaction of the functional groups of the CQDs with HCoV-229E entry receptors; surprisingly, an equally large inhibition activity was obsd. at the viral replication step.
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76Ting, D.; Dong, N.; Fang, L.; Lu, J.; Bi, J.; Xiao, S.; Han, H. Multisite Inhibitors for Enteric Coronavirus: Antiviral Cationic Carbon Dots Based on Curcumin. ACS Appl. Nano Mater. 2018, 1, 5451– 5459, DOI: 10.1021/acsanm.8b00779Google ScholarThere is no corresponding record for this reference.
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77Tong, T.; Hu, H.; Zhou, J.; Deng, S.; Zhang, X.; Tang, W.; Fang, L.; Xiao, S.; Liang, J. Glycyrrhizic-Acid-Based Carbon Dots with High Antiviral Activity by Multisite Inhibition Mechanisms. Small 2020, 16, 1906206, DOI: 10.1002/smll.201906206Google Scholar77https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXjt12rsLY%253D&md5=9dedd5a9f24d0af04d2fecc19d07deb1Glycyrrhizic-Acid-Based Carbon Dots with High Antiviral Activity by Multisite Inhibition MechanismsTong, Ting; Hu, Hongwei; Zhou, Junwei; Deng, Shuangfei; Zhang, Xiaotong; Tang, Wantao; Fang, Liurong; Xiao, Shaobo; Liang, JiangongSmall (2020), 16 (13), 1906206CODEN: SMALBC; ISSN:1613-6810. (Wiley-VCH Verlag GmbH & Co. KGaA)With the gradual usage of carbon dots (CDs) in the area of antiviral research, attempts have been stepped up to develop new antiviral CDs with high biocompatibility and antiviral effects. In this study, a kind of highly biocompatible CDs (Gly-CDs) is synthesized from active ingredient (glycyrrhizic acid) of Chinese herbal medicine by a hydrothermal method. Using the porcine reproductive and respiratory syndrome virus (PRRSV) as a model, it is found that the Gly-CDs inhibit PRRSV proliferation by up to 5 orders of viral titers. Detailed investigations reveal that Gly-CDs can inhibit PRRSV invasion and replication, stimulate antiviral innate immune responses, and inhibit the accumulation of intracellular reactive oxygen species (ROS) caused by PRRSV infection. Proteomics anal. demonstrates that Gly-CDs can stimulate cells to regulate the expression of some host restriction factors, including DDX53 and NOS3, which are directly related to PRRSV proliferation. Moreover, it is found that Gly-CDs also remarkably suppress the propagation of other viruses, such as pseudorabies virus (PRV) and porcine epidemic diarrhea virus (PEDV), suggesting the broad antiviral activity of Gly-CDs. The integrated results demonstrate that Gly-CDs possess extraordinary antiviral activity with multisite inhibition mechanisms, providing a promising candidate for alternative therapy for PRRSV infection.
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78Huang, S.; Gu, J.; Ye, J.; Fang, B.; Wan, S.; Wang, C.; Ashraf, U.; Li, Q.; Wang, X.; Shao, L.; Song, Y.; Zheng, X.; Cao, F.; Cao, S. Benzoxazine Monomer Derived Carbon Dots as a Broad-Spectrum Agent to Block Viral Infectivity. J. Colloid Interface Sci. 2019, 542, 198– 206, DOI: 10.1016/j.jcis.2019.02.010Google Scholar78https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXislOgs7Y%253D&md5=7c9871dbbe6c29af794aa35101000c71Benzoxazine monomer derived carbon dots as a broad-spectrum agent to block viral infectivityHuang, Shaomei; Gu, Jiangjiang; Ye, Jing; Fang, Bin; Wan, Shengfeng; Wang, Caoyu; Ashraf, Usama; Li, Qi; Wang, Xugang; Shao, Lin; Song, Yunfeng; Zheng, Xinsheng; Cao, Feifei; Cao, ShengboJournal of Colloid and Interface Science (2019), 542 (), 198-206CODEN: JCISA5; ISSN:0021-9797. (Elsevier B.V.)Multiple viruses can cause infection and death of millions annually. Of these, flaviviruses are found to be highly prevalent in recent years with no distinctive antiviral therapies. Therefore, there is a desperate need for broad-spectrum antiviral drugs that can be active against a large no. of existing and emerging viruses. Herein, we prepd. a kind of benzoxazine monomer derived carbon dots (BZM-CDs) and demonstrated their infection-blocking ability against life-threatening flaviviruses (Japanese encephalitis, Zika, and dengue viruses) and non-enveloped viruses (porcine parvovirus and adenovirus-assocd. virus). It was found that BZM-CDs could directly bind to the surface of the virion, and eventually the first step of virus-cell interaction was impeded. The developed nanoparticles are active against both flaviviruses and non-enveloped viruses in vitro. Thus, the application of BZM-CDs may constitute an intriguing broad-spectrum approach to rein in viral infections.
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79Zoppe, J. O.; Ruottinen, V.; Ruotsalainen, J.; Rönkkö, S.; Johansson, L.-S.; Hinkkanen, A.; Järvinen, K.; Seppälä, J. Synthesis of Cellulose Nanocrystals Carrying Tyrosine Sulfate Mimetic Ligands and Inhibition of Alphavirus Infection. Biomacromolecules 2014, 15, 1534– 1542, DOI: 10.1021/bm500229dGoogle Scholar79https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXktlSqs7o%253D&md5=5d947eb13327f3e7e8af8db90f6fac24Synthesis of Cellulose Nanocrystals Carrying Tyrosine Sulfate Mimetic Ligands and Inhibition of Alphavirus InfectionZoppe, Justin O.; Ruottinen, Ville; Ruotsalainen, Janne; Ronkko, Seppo; Johansson, Leena-Sisko; Hinkkanen, Ari; Jarvinen, Kristiina; Seppala, JukkaBiomacromolecules (2014), 15 (4), 1534-1542CODEN: BOMAF6; ISSN:1525-7797. (American Chemical Society)We present two facile approaches for introducing multivalent displays of tyrosine sulfate mimetic ligands on the surface of cellulose nanocrystals (CNCs) for application as viral inhibitors. We tested the efficacy of cellulose nanocrystals, prepd. either from cotton fibers or Whatman filter paper, to inhibit alphavirus infectivity in Vero (B) cells. Cellulose nanocrystals were produced by sulfuric acid hydrolysis leading to nanocrystal surfaces decorated with anionic sulfate groups. When the fluorescent marker expressing Semliki Forest virus vector, VA7-EGFP, was incubated with CNCs, strong inhibition of virus infectivity was achieved, up to 100 and 88% for cotton and Whatman CNCs, resp. When surface sulfate groups of CNCs were exchanged for tyrosine sulfate mimetic groups (i.e. Ph sulfonates), improved viral inhibition was attained. Our observations suggest that the conjugation of target-specific functionalities to CNC surfaces provides a means to control their antiviral activity. Multivalent CNCs did not cause observable in vitro cytotoxicity to Vero (B) cells or human corneal epithelial (HCE-T) cells, even within the 100% virus-inhibitory concns. Based on the similar chem. of known polyanionic inhibitors, our results suggest the potential application of CNCs as inhibitors of other viruses, such as human immunodeficiency virus (HIV) and herpes simplex viruses.
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80Lima, T. L. C.; Feitosa, R. D. C.; Dos Santos-Silva, E.; Dos Santos-Silva, A. M.; Siqueira, E. M. D. S.; Machado, P. R. L.; Cornélio, A. M.; Do Egito, E. S. T.; Fernandes-Pedrosa, M. D. F.; Farias, K. J. S.; Da Silva-Júnior, A. A. Improving Encapsulation of Hydrophilic Chloroquine Diphosphate into Biodegradable Nanoparticles: A Promising Approach against Herpes Virus Simplex-1 Infection. Pharmaceutics 2018, 10, 255, DOI: 10.3390/pharmaceutics10040255Google Scholar80https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXitFWktLnI&md5=f20bc5723458023af61f77f41575557fImproving encapsulation of hydrophilic chloroquine diphosphate into biodegradable nanoparticles: a promising approach against herpes virus simplex-1 infectionLima, Tabata Loise Cunha; de Carvalho Feitosa, Renata; dos Santos-Silva, Emanuell; dos Santos-Silva, Alaine Maria; da Silva Siqueira, Emerson Michell; Machado, Paula Renata Lima; Cornelio, Alianda Maira; do Egito, Eryvaldo Socrates Tabosa; de Freitas Fernandes-Pedrosa, Matheus; Farias, Kleber Juvenal Silva; da Silva-Junior, Arnobio AntonioPharmaceutics (2018), 10 (4), 255CODEN: PHARK5; ISSN:1999-4923. (MDPI AG)Chloroquine diphosphate (CQ) is a hydrophilic drug with low entrapment efficiency in hydrophobic nanoparticles (NP). Herpes simplex virus type 1 (HSV-1) is an enveloped double-stranded DNA virus worldwide known as a common human pathogen. This study aims to develop chloroquine-loaded poly(lactic acid) (PLA) nanoparticles (CQ-NP) to improve the chloroquine anti- HSV-1 efficacy. CQ-NP were successfully prepd. using a modified emulsification-solvent evapn. method. Physicochem. properties of the NP were monitored using dynamic light scattering, at. force microscopy, drug loading efficiency, and drug release studies. Spherical nanoparticles were produced with modal diam. of <300 nm, zeta potential of -20 mv and encapsulation efficiency of 64.1%. In vitro assays of CQ-NP performed in Vero E6 cells, using the MTT-assay, revealed different cytotoxicity levels. Blank nanoparticles (B-NP) were biocompatible. Finally, the antiviral activity tested by the plaque redn. assay revealed greater efficacy for CQ-NP compared to CQ at concns. equal to or lower than 20 μg mL-1 (p < 0.001). On the other hand, the B-NP had no antiviral activity. The CQ-NP has shown feasible properties and great potential to improve the antiviral activity of drugs.
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81Kong, B.; Moon, S.; Kim, Y.; Heo, P.; Jung, Y.; Yu, S.-H.; Chung, J.; Ban, C.; Kim, Y. H.; Kim, P.; Hwang, B. J.; Chung, W.-J.; Shin, Y.-K.; Seong, B. L.; Kweon, D.-H. Virucidal Nano-Perforator of Viral Membrane Trapping Viral Rnas in the Endosome. Nat. Commun. 2019, 10, 185, DOI: 10.1038/s41467-018-08138-1Google Scholar81https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3cjhsVWisQ%253D%253D&md5=1c175360d72ec1b439569abcb71d1708Virucidal nano-perforator of viral membrane trapping viral RNAs in the endosomeKong Byoungjae; Moon Seokoh; Kim Yuna; Heo Paul; Jung Younghun; Yu Seok-Hyeon; Chung Jinhyo; Ban Choongjin; Chung Woo-Jae; Kweon Dae-Hyuk; Kim Yong Ho; Kweon Dae-Hyuk; Kim Paul; Hwang Beom Jeung; Seong Baik Lin; Shin Yeon-KyunNature communications (2019), 10 (1), 185 ISSN:.Membrane-disrupting agents that selectively target virus versus host membranes could potentially inhibit a broad-spectrum of enveloped viruses, but currently such antivirals are lacking. Here, we develop a nanodisc incorporated with a decoy virus receptor that inhibits virus infection. Mechanistically, nanodiscs carrying the viral receptor sialic acid bind to influenza virions and are co-endocytosed into host cells. At low pH in the endosome, the nanodiscs rupture the viral envelope, trapping viral RNAs inside the endolysosome for enzymatic decomposition. In contrast, liposomes containing a decoy receptor show weak antiviral activity due to the lack of membrane disruption. The nanodiscs inhibit influenza virus infection and reduce morbidity and mortality in a mouse model. Our results suggest a new class of antivirals applicable to other enveloped viruses that cause irreversible physical damage specifically to virus envelope by viruses' own fusion machine. In conclusion, the lipid nanostructure provides another dimension for antiviral activity of decoy molecules.
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82Hoffmann, M.; Kleine-Weber, H.; Schroeder, S.; Krüger, N.; Herrler, T.; Erichsen, S.; Schiergens, T. S.; Herrler, G.; Wu, N.-H.; Nitsche, A.; Müller, M. A.; Drosten, C.; Pöhlmann, S. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell 2020, 181, 271– 280, DOI: 10.1016/j.cell.2020.02.052Google Scholar82https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXktl2qtb8%253D&md5=60aea5c939a2d4df034a91d6198fb3efSARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease InhibitorHoffmann, Markus; Kleine-Weber, Hannah; Schroeder, Simon; Krueger, Nadine; Herrler, Tanja; Erichsen, Sandra; Schiergens, Tobias S.; Herrler, Georg; Wu, Nai-Huei; Nitsche, Andreas; Mueller, Marcel A.; Drosten, Christian; Poehlmann, StefanCell (Cambridge, MA, United States) (2020), 181 (2), 271-280.e8CODEN: CELLB5; ISSN:0092-8674. (Cell Press)The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clin. use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.
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83Ou, X.; Liu, Y.; Lei, X.; Li, P.; Mi, D.; Ren, L.; Guo, L.; Guo, R.; Chen, T.; Hu, J.; Xiang, Z.; Mu, Z.; Chen, X.; Chen, J.; Hu, K.; Jin, Q.; Wang, J.; Qian, Z. Characterization of Spike Glycoprotein of SARS-CoV-2 on Virus Entry and Its Immune Cross-Reactivity with SARS-CoV. Nat. Commun. 2020, 11, 1620, DOI: 10.1038/s41467-020-15562-9Google Scholar83https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXlvFyjt78%253D&md5=6b0b1ef5a68f4a35da4aabecb0f99544Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoVOu, Xiuyuan; Liu, Yan; Lei, Xiaobo; Li, Pei; Mi, Dan; Ren, Lili; Guo, Li; Guo, Ruixuan; Chen, Ting; Hu, Jiaxin; Xiang, Zichun; Mu, Zhixia; Chen, Xing; Chen, Jieyong; Hu, Keping; Jin, Qi; Wang, Jianwei; Qian, ZhaohuiNature Communications (2020), 11 (1), 1620CODEN: NCAOBW; ISSN:2041-1723. (Nature Research)Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002-2003, MERS-CoV in 2012, and the newly emerged SARS-CoV-2 in late 2019. However, little is currently known about the biol. of SARS-CoV-2. Here, using SARS-CoV-2 S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) is the receptor for SARS-CoV-2, find that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L are crit. for entry, and that SARS-CoV-2 S protein is less stable than SARS-CoV S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry of SARS-CoV S but not SARS-CoV-2 S pseudovirions. Further studies using recovered SARS and COVID-19 patients' sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for SARS-CoV-2.
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84Wang, Q.; Zhang, Y.; Wu, L.; Niu, S.; Song, C.; Zhang, Z.; Lu, G.; Qiao, C.; Hu, Y.; Yuen, K.-Y.; Wang, Q.; Zhou, H.; Yan, J.; Qi, J. Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2. Cell 2020, 181, 894– 904, DOI: 10.1016/j.cell.2020.03.045Google Scholar84https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXmvFGrur4%253D&md5=188108e44f104860d4a2b83707ce7230Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2Wang, Qihui; Zhang, Yanfang; Wu, Lili; Niu, Sheng; Song, Chunli; Zhang, Zengyuan; Lu, Guangwen; Qiao, Chengpeng; Hu, Yu; Yuen, Kwok-Yung; Wang, Qisheng; Zhou, Huan; Yan, Jinghua; Qi, JianxunCell (Cambridge, MA, United States) (2020), 181 (4), 894-904.e9CODEN: CELLB5; ISSN:0092-8674. (Cell Press)The recent emergence of a novel coronavirus (SARS-CoV-2) in China has caused significant public health concerns. Recently, ACE2 was reported as an entry receptor for SARS-CoV-2. In this study, we present the crystal structure of the C-terminal domain of SARS-CoV-2 (SARS-CoV-2-CTD) spike (S) protein in complex with human ACE2 (hACE2), which reveals a hACE2-binding mode similar overall to that obsd. for SARS-CoV. However, at. details at the binding interface demonstrate that key residue substitutions in SARS-CoV-2-CTD slightly strengthen the interaction and lead to higher affinity for receptor binding than SARS-RBD. Addnl., a panel of murine monoclonal antibodies (mAbs) and polyclonal antibodies (pAbs) against SARS-CoV-S1/receptor-binding domain (RBD) were unable to interact with the SARS-CoV-2 S protein, indicating notable differences in antigenicity between SARS-CoV and SARS-CoV-2. These findings shed light on the viral pathogenesis and provide important structural information regarding development of therapeutic countermeasures against the emerging virus.
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85Hu, T. Y.; Frieman, M.; Wolfram, J. Insights from Nanomedicine into Chloroquine Efficacy against Covid-19. Nat. Nanotechnol. 2020, 15, 247– 249, DOI: 10.1038/s41565-020-0674-9Google Scholar85https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXlsVeitbc%253D&md5=5982dadec9e67ff2201836264a82a858Insights from nanomedicine into chloroquine efficacy against COVID-19Hu, Tony Y.; Frieman, Matthew; Wolfram, JoyNature Nanotechnology (2020), 15 (4), 247-249CODEN: NNAABX; ISSN:1748-3387. (Nature Research)A review. Chloroquine - an approved malaria drug - is known in nanomedicine research for the investigation of nanoparticle uptake in cells, and may have potential for the treatment of COVID-19.
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86Iannazzo, D.; Pistone, A.; Ferro, S.; De Luca, L.; Monforte, A. M.; Romeo, R.; Buemi, M. R.; Pannecouque, C. Graphene Quantum Dots Based Systems as HIV Inhibitors. Bioconjugate Chem. 2018, 29, 3084– 3093, DOI: 10.1021/acs.bioconjchem.8b00448Google Scholar86https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhsV2lsLjK&md5=fe5063bada938f85bc6214a6cab5d928Graphene Quantum Dots Based Systems As HIV InhibitorsIannazzo, Daniela; Pistone, Alessandro; Ferro, Stefania; De Luca, Laura; Monforte, Anna Maria; Romeo, Roberto; Buemi, Maria Rosa; Pannecouque, ChristopheBioconjugate Chemistry (2018), 29 (9), 3084-3093CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)Graphene quantum dots (GQD) are the next generation of nanomaterials with great potential in drug delivery and target-specific HIV inhibition. In this study we investigated the antiviral activity of graphene based nanomaterials by using water-sol. GQD synthesized from multiwalled carbon nanotubes (MWCNT) through prolonged acidic oxidn. and exfoliation and compared their anti-HIV activity with that exerted by reverse transcriptase inhibitors (RTI) conjugated with the same nanomaterial. The antiretroviral agents chosen in this study, CHI499 and CDF119, belong to the class of non-nucleoside reverse transcriptase inhibitors (NNRTI). From this study emerged the RTI-conjugated compd. GQD-CHI499 as a good potential candidate for HIV treatment, showing an IC50 of 0.09 μg/mL and an EC50 value in cell of 0.066 μg/mL. The target of action in the replicative cycle of HIV of the drug conjugated samples GQD-CHI499 and GQD-CDF119 was also investigated by a time of addn. (TOA) method, showing for both conjugated samples a mechanism of action similar to that exerted by NNRTI drugs.
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87Galdiero, S.; Falanga, A.; Vitiello, M.; Cantisani, M.; Marra, V.; Galdiero, M. Silver Nanoparticles as Potential Antiviral Agents. Molecules 2011, 16, 8894– 8918, DOI: 10.3390/molecules16108894Google Scholar87https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhsVOqurrK&md5=a41d01ceef275d779deb1509c0ab6fefSilver nanoparticles as potential antiviral agentsGaldiero, Stefania; Falanga, Annarita; Vitiello, Mariateresa; Cantisani, Marco; Marra, Veronica; Galdiero, MassimilianoMolecules (2011), 16 (), 8894-8918CODEN: MOLEFW; ISSN:1420-3049. (MDPI AG)A review. Virus infections pose significant global health challenges, esp. in view of the fact that the emergence of resistant viral strains and the adverse side effects assocd. with prolonged use continue to slow down the application of effective antiviral therapies. This makes imperative the need for the development of safe and potent alternatives to conventional antiviral drugs. In the present scenario, nanoscale materials have emerged as novel antiviral agents for the possibilities offered by their unique chem. and phys. properties. Silver nanoparticles have mainly been studied for their antimicrobial potential against bacteria, but have also proven to be active against several types of viruses including human immunodeficiency virus, hepatitis B virus, herpes simplex virus, respiratory syncytial virus, and monkey pox virus. The use of metal nanoparticles provides an interesting opportunity for novel antiviral therapies. Since metals may attack a broad range of targets in the virus there is a lower possibility to develop resistance as compared to conventional antivirals. The present review focuses on the development of methods for the prodn. of silver nanoparticles and on their use as antiviral therapeutics against pathogenic viruses.
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88Yen, H.-J.; Hsu, S.-H.; Tsai, C.-L. Cytotoxicity and Immunological Response of Gold and Silver Nanoparticles of Different Sizes. Small 2009, 5, 1553– 1561, DOI: 10.1002/smll.200900126Google Scholar88https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXos1Cqt7o%253D&md5=e1a847ba1093bce4dba630df403e1bffCytotoxicity and immunological response of gold and silver nanoparticles of different sizesYen, Hung-Jen; Hsu, Shan-hui; Tsai, Ching-LinSmall (2009), 5 (13), 1553-1561CODEN: SMALBC; ISSN:1613-6810. (Wiley-VCH Verlag GmbH & Co. KGaA)The immunol. response of macrophages to phys. produced pure Au and Ag nanoparticles (NPs) (in 3 different sizes) is investigated in vitro. The treatment of either type of NP at ≥10 ppm dramatically decreases the population and increases the size of the macrophages. Both NPs enter the cells but only AuNPs (esp. those with smaller diam.) up-regulate the expressions of proinflammatory genes interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF-α). Transmission electron microscopy images show that AuNPs and AgNPs are both trapped in vesicles in the cytoplasm, but only AuNPs are organized into a circular pattern. It is speculated that part of the neg. charged AuNPs might adsorb serum protein and enter cells via the more complicated endocytotic pathway, which results in higher cytotoxicity and immunol. response of AuNPs as compared to AgNPS.
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89Johnston, H. J.; Hutchison, G.; Christensen, F. M.; Peters, S.; Hankin, S.; Stone, V. A Review of the In Vivo and In Vitro Toxicity of Silver and Gold Particulates: Particle Attributes and Biological Mechanisms Responsible for the Observed Toxicity. Crit. Rev. Toxicol. 2010, 40, 328– 346, DOI: 10.3109/10408440903453074Google Scholar89https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXjsFeguro%253D&md5=bb89818ce201ff712139ef70cd118bb1A review of the in vivo and in vitro toxicity of silver and gold particulates: Particle attributes and biological mechanisms responsible for the observed toxicityJohnston, Helinor J.; Hutchison, Gary; Christensen, Frans M.; Peters, Sheona; Hankin, Steve; Stone, VickiCritical Reviews in Toxicology (2010), 40 (4), 328-346CODEN: CRTXB2; ISSN:1040-8444. (Informa Healthcare)A review. This review is concerned with evaluating the toxicity assocd. with human exposure to silver and gold nanoparticles (NPs), due to the relative abundance of toxicity data available for these particles, when compared to other metal particulates. This has allowed knowledge on the current understanding of the field to be gained, and has demonstrated where gaps in knowledge are. It is anticipated that evaluating the hazards assocd. with silver and gold particles will ultimately enable risk assessments to be completed, by combining this information with knowledge on the level of human exposure. The quantity of available hazard information for metals is greatest for silver particulates, due to its widespread inclusion within a no. of diverse products (including clothes and wound dressings), which primarily arises from its antibacterial behavior. Gold has been used on numerous occasions to assess the biodistribution and cellular uptake of NPs following exposure. Inflammatory, oxidative, genotoxic, and cytotoxic consequences are assocd. with silver particulate exposure, and are inherently linked. The primary site of gold and silver particulate accumulation has been consistently demonstrated to be the liver, and it is therefore relevant that a no. of in vitro investigations have focused on this potential target organ. However, in general there is a lack of in vivo and in vitro toxicity information that allows correlations between the findings to be made. Instead a focus on the tissue distribution of particles following exposure is evident within the available literature, which can be useful in directing appropriate in vitro experimentation by revealing potential target sites of toxicity. The exptl. design has the potential to impact on the toxicol. observations, and in particular the use of excessively high particle concns. has been obsd. As witnessed for other particle types, gold and silver particle sizes are influential in dictating the obsd. toxicity, with smaller particles exhibiting a greater response than their larger counterparts, and this is likely to be driven by differences in particle surface area, when administered at an equal-mass dose. A major obstacle, at present, is deciphering whether the responses related to silver nanoparticulate exposure derive from their small size, or particle dissoln. contributes to the obsd. toxicity. Alternatively, a combination of both may be responsible, as the release of ions would be expected to be greater for smaller particles.
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90Bar-Ilan, O.; Albrecht, R. M.; Fako, V. E.; Furgeson, D. Y. Toxicity Assessments of Multisized Gold and Silver Nanoparticles in Zebrafish Embryos. Small 2009, 5, 1897– 1910, DOI: 10.1002/smll.200801716Google Scholar90https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXps1ykurg%253D&md5=8703eb895b5cae658bfc6fd191de1decToxicity Assessments of Multisized Gold and Silver Nanoparticles in Zebrafish EmbryosBar-Ilan, Ofek; Albrecht, Ralph M.; Fako, Valerie E.; Furgeson, Darin Y.Small (2009), 5 (16), 1897-1910CODEN: SMALBC; ISSN:1613-6810. (Wiley-VCH Verlag GmbH & Co. KGaA)The potential toxicity of nanoparticles is addressed by utilizing a putative attractive model in developmental biol. and genetics: the zebrafish (Danio rerio). Transparent zebrafish embryos, possessing a high degree of homol. to the human genome, offer an economically feasible, medium-throughput screening platform for noninvasive real-time assessments of toxicity. Using colloidal silver (cAg) and gold nanoparticles (cAu) in a panoply of sizes (3, 10, 50, and 100 nm) and a semiquant. scoring system, it is found that cAg produces almost 100% mortality at 120 h post-fertilization, while cAu produces less than 3% mortality at the same time point. Furthermore, while cAu induces minimal sublethal toxic effects, cAg treatments generate a variety of embryonic morphol. malformations. Both cAg and cAu are taken up by the embryos and control expts., suggesting that cAg toxicity is caused by the nanoparticles themselves or Ag+ that is formed during in vivo nanoparticle destabilization. Although cAg toxicity is slightly size dependent at certain concns. and time points, the most striking result is that parallel sizes of cAg and cAu induce significantly different toxic profiles, with the former being toxic and the latter being inert in all exposed sizes. Therefore, it is proposed that nanoparticle chem. is as, if not more, important than specific nanosizes at inducing toxicity in vivo. Ultimately such assessments using the zebrafish embryo model should lead to the identification of nanomaterial characteristics that afford minimal or no toxicity and guide more rational designs of materials on the nanoscale.
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91Li, Y.; Lin, Z.; Gong, G.; Guo, M.; Xu, T.; Wang, C.; Zhao, M.; Xia, Y.; Tang, Y.; Zhong, J.; Chen, Y.; Hua, L.; Huang, Y.; Zeng, F.; Zhu, B. Inhibition of H1N1 Influenza Virus-Induced Apoptosis by Selenium Nanoparticles Functionalized with Arbidol through ROS-Mediated Signaling Pathways. J. Mater. Chem. B 2019, 7, 4252– 4262, DOI: 10.1039/C9TB00531EGoogle Scholar91https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtVOgtLbE&md5=f38cb73793e9c38f152aeb674ae946d2Inhibition of H1N1 influenza virus-induced apoptosis by selenium nanoparticles functionalized with arbidol through ROS-mediated signaling pathwaysLi, Yinghua; Lin, Zhengfang; Gong, Guifang; Guo, Min; Xu, Tiantian; Wang, Changbing; Zhao, Mingqi; Xia, Yu; Tang, Ying; Zhong, Jiayu; Chen, Yi; Hua, Liang; Huang, Yanqing; Zeng, Fangling; Zhu, BingJournal of Materials Chemistry B: Materials for Biology and Medicine (2019), 7 (27), 4252-4262CODEN: JMCBDV; ISSN:2050-7518. (Royal Society of Chemistry)As an effective antiviral agent, the clin. application of arbidol is limited by the appearance of drug-resistant viruses. To overcome the limitation of drug-resistance, the use of modified nanoparticles with biol. materials to explore novel anti-influenza drugs is developing rapidly. The antiviral activity of selenium nanoparticles (SeNPs) has attracted increasing attention in the biomedical field. Surface modified SeNPs by arbidol (Se@ARB) with superior antiviral properties towards drug resistance are synthesized in the current study. Arbidol decoration of SeNPs (Se@ARB) with less toxicity had obviously inhibited H1N1 infection. Se@ARB interfered with the interaction between the H1N1 influenza virus and the host cells by suppressing the activity of hemagglutinin (HA) and neuraminidase (NA). Se@ARB could prevent H1N1 from infecting MDCK cells and block DNA fragmentation and chromatin condensation. Furthermore, Se@ARB evidently inhibited the generation of reactive oxygen species (ROS). In vivo expts. revealed that Se@ARB prevents lung injury in H1N1 infected mice through hematoxylin and eosin staining. The TUNEL test of lung tissues shows that DNA damage reached a high level but reduced substantially when treated with Se@ARB. Immunohistochem. assay revealed that activation of caspase-3, AKT and MAPK signaling pathways was restrained by Se@ARB treatment. These results demonstrate that Se@ARB is a promising antiviral pharmaceutical candidate for the inhibition of H1N1 influenza virus.
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92Milewska, A.; Kaminski, K.; Ciejka, J.; Kosowicz, K.; Zeglen, S.; Wojarski, J.; Nowakowska, M.; Szczubiałka, K.; Pyrc, K. HTCC: Broad Range Inhibitor of Coronavirus Entry. PLoS One 2016, 11, e0156552, DOI: 10.1371/journal.pone.0156552Google Scholar92https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhsFKhsb%252FK&md5=a6037aafdf3c7e162b40bb92abcfc822HTCC: broad range inhibitor of coronavirus entryMilewska, Aleksandra; Kaminski, Kamil; Ciejka, Justyna; Kosowicz, Katarzyna; Zeglen, Slawomir; Wojarski, Jacek; Nowakowska, Maria; Szczubialka, Krzysztof; Pyrc, KrzysztofPLoS One (2016), 11 (6), e0156552/1-e0156552/17CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)To date, six human coronaviruses have been known, all of which are assocd. with respiratory infections in humans. With the exception of the highly pathogenic SARS and MERS coronaviruses, human coronaviruses (HCoV-NL63, HCoV-OC43, HCoV-229E, and HCoVHKU1) circulate worldwide and typically cause the common cold. In most cases, infection with these viruses does not lead to severe disease, although acute infections in infants, the elderly, and immunocompromised patients may progress to severe disease requiring hospitalization. Importantly, no drugs against human coronaviruses exist, and only supportive therapy is available. Previously, we proposed the cationically modified chitosan, N-(2- hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC), and its hydrophobicallymodified deriv. (HM-HTCC) as potent inhibitors of the coronavirus HCoV-NL63. Here, we show that HTCC inhibits interaction of a virus with its receptor and thus blocks the entry. Further, we demonstrate that HTCC polymers with different degrees of substitution act as effective inhibitors of all low-pathogenic human coronaviruses.
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93Raghuwanshi, D.; Mishra, V.; Das, D.; Kaur, K.; Suresh, M. R. Dendritic Cell Targeted Chitosan Nanoparticles for Nasal DNA Immunization against SARS CoV Nucleocapsid Protein. Mol. Pharmaceutics 2012, 9, 946– 956, DOI: 10.1021/mp200553xGoogle Scholar93https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XislSkt7Y%253D&md5=b5b666a5b8222807266e06bc79fbfd36Dendritic Cell Targeted Chitosan Nanoparticles for Nasal DNA Immunization against SARS CoV Nucleocapsid ProteinRaghuwanshi, Dharmendra; Mishra, Vivek; Das, Dipankar; Kaur, Kamaljit; Suresh, Mavanur R.Molecular Pharmaceutics (2012), 9 (4), 946-956CODEN: MPOHBP; ISSN:1543-8384. (American Chemical Society)This work investigates the formulation and in vivo efficacy of dendritic cell (DC) targeted plasmid DNA loaded biotinylated chitosan nanoparticles for nasal immunization against nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) as antigen. The induction of antigen-specific mucosal and systemic immune response at the site of virus entry is a major challenge for vaccine design. Here, we designed a strategy for noninvasive receptor mediated gene delivery to nasal resident DCs. The pDNA loaded biotinylated chitosan nanoparticles were prepd. using a complex coacervation process and characterized for size, shape, surface charge, plasmid DNA loading and protection against nuclease digestion. The pDNA loaded biotinylated chitosan nanoparticles were targeted with bifunctional fusion protein (bfFp) vector for achieving DC selective targeting. The bfFp is a recombinant fusion protein consisting of truncated core-streptavidin fused with anti-DEC-205 single chain antibody (scFv). The core-streptavidin arm of fusion protein binds with biotinylated nanoparticles, while anti-DEC-205 scFv imparts targeting specificity to DC DEC-205 receptor. We demonstrate that intranasal administration of bfFp targeted formulations along with anti-CD40 DC maturation stimuli enhanced magnitude of mucosal IgA as well as systemic IgG against N protein. The strategy led to the detection of augmented levels of N protein specific systemic IgG and nasal IgA antibodies. However, following intranasal delivery of naked pDNA no mucosal and systemic immune responses were detected. A parallel comparison of targeted formulations using i.m. and intranasal routes showed that the i.m. route is superior for induction of systemic IgG responses compared with the intranasal route. Our results suggest that targeted pDNA delivery through a noninvasive intranasal route can be a strategy for designing low-dose vaccines.
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94Alghrair, Z. K.; Fernig, D. G.; Ebrahimi, B. Enhanced Inhibition of Influenza Virus Infection by Peptide-Noble-Metal Nanoparticle Conjugates. Beilstein J. Nanotechnol. 2019, 10, 1038– 1047, DOI: 10.3762/bjnano.10.104Google Scholar94https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtVGgtLrF&md5=67095809fbd256a6a9109040860cb7f8Enhanced inhibition of influenza virus infection by peptide-noble-metal nanoparticle conjugatesAlghrair, Zaid K.; Fernig, David G.; Ebrahimi, BahramBeilstein Journal of Nanotechnology (2019), 10 (), 1038-1047CODEN: BJNEAH; ISSN:2190-4286. (Beilstein-Institut zur Foerderung der Chemischen Wissenschaften)We have explored the potential for noble-metal nanoparticle conjugates of FluPep to enhance its antiviral activity and to det. their potential as a delivery platform for FluPep. FluPep ligand is FluPep extended at its N-terminus with the sequence CVVVTAAA, to allow for its incorporation into a mixed-matrix ligand shell of a peptidol and an alkanethiol ethylene glycol consisting of 70% CVVVTol and 30% HS(CH2)11 (OC2H4)4OH (mol/mol). Gold and silver nanoparticles (ca. 10 nm diam.) with up to 5% (mol/mol) FluPep ligand remained as stable as the control of mixed-matrix-passivated nanoparticles in a variety of tests, including ligand exchange with dithiothreitol. The free FluPep ligand peptide was found to inhibit viral plaque formation in canine MDCK cells (IC50 = 2.1 nM), but was less potent than FluPep itself (IC50 = 140 pM). Nanoparticles functionalised with FluPep ligand showed enhanced antiviral activity compared to the free peptides. The IC50 value of the FluPep-functionalised nanoparticles decreased as the grafting d. of FluPep ligand increased from 0.03% to 5% (both mol/mol), with IC50 values down to about 10% of that of the corresponding free peptide. The data demonstrate that conjugation of FluPep to gold and silver nanoparticles enhances its antiviral potency; the antimicrobial activity of silver ions may enable the design of even more potent antimicrobial inhibitors, capable of targeting both influenza and bacterial co-infections.
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95Mori, Y.; Ono, T.; Miyahira, Y.; Nguyen, V. Q.; Matsui, T.; Ishihara, M. Antiviral Activity of Silver Nanoparticle/Chitosan Composites against H1n1 Influenza a Virus. Nanoscale Res. Lett. 2013, 8, 93– 93, DOI: 10.1186/1556-276X-8-93Google Scholar95https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXht1Wisb7K&md5=1eb2644efd696c62ed295f8ee0d5d88cAntiviral activity of silver nanoparticle/chitosan composites against H1N1 influenza A virusMori, Yasutaka; Ono, Takeshi; Miyahira, Yasushi; Nguyen, Vinh Quang; Matsui, Takemi; Ishihara, MasayukiNanoscale Research Letters (2013), 8 (1), 93/1-93/6CODEN: NRLAAD; ISSN:1556-276X. (Springer)Silver nanoparticle (Ag NP)/chitosan (Ch) composites with antiviral activity against H1N1 influenza A virus were prepd. The Ag NP/Ch composites were obtained as yellow or brown floc-like powders following reaction at room temp. in aq. medium. Ag NPs (3.5, 6.5, and 12.9 nm av. diams.) were embedded into the chitosan matrix without aggregation or size alternation. The antiviral activity of the Ag NP/Ch composites was evaluated by comparing the TCID50 ratio of viral suspensions treated with the composites to untreated suspensions. For all sizes of Ag NPs tested, antiviral activity against H1N1 influenza A virus increased as the concn. of Ag NPs increased; chitosan alone exhibited no antiviral activity. Size dependence of the Ag NPs on antiviral activity was also obsd.: antiviral activity was generally stronger with smaller Ag NPs in the composites. These results indicate that Ag NP/Ch composites interacting with viruses exhibit antiviral activity.
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96Du, T.; Lu, J.; Liu, L.; Dong, N.; Fang, L.; Xiao, S.; Han, H. Antiviral Activity of Graphene Oxide–Silver Nanocomposites by Preventing Viral Entry and Activation of the Antiviral Innate Immune Response. ACS Appl. Bio Mater. 2018, 1, 1286– 1293, DOI: 10.1021/acsabm.8b00154Google Scholar96https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXitVansbrM&md5=b04d516c949e51fbd322afc4d8c18677Antiviral Activity of Graphene Oxide-Silver Nanocomposites by Preventing Viral Entry and Activation of the Antiviral Innate Immune ResponseDu, Ting; Lu, Jian; Liu, Lingzhi; Dong, Nan; Fang, Liurong; Xiao, Shaobo; Han, HeyouACS Applied Bio Materials (2018), 1 (5), 1286-1293CODEN: AABMCB; ISSN:2576-6422. (American Chemical Society)Developing nanomaterials-based antimicrobial agents has shown a widespread promise. In this study, silver nanoparticle-modified graphene oxide (GO-AgNPs) nanocomposites were self-assembled via interfacial electrostatic force. By using the porcine reproductive and respiratory syndrome virus (PRRSV) as a pattern, the antiviral effect of the as-prepd. GO-AgNPs nanocomposites on the replication of virus was investigated. The results indicated that exposure with GO-AgNPs nanocomposites could obviously suppress PRRSV infection. It was found that GO-AgNPs nanocomposites exhibited a better inhibitory effect compared with AgNPs and GO. By selecting the porcine epidemic diarrhea virus (PEDV) as a contrast virus, GO-AgNPs nanocomposites were proven to have a broad antiviral activity. Mechanism studies showed that GO-AgNPs nanocomposites might prevent PRRSV from entering the host cells, with 59.2% inhibition efficiency. Meanwhile, GO-AgNPs nanocomposite treatment enhances the prodn. of interferon-α (IFN-α) and IFN-stimulating genes (ISGs), which can directly inhibit the proliferation of virus. Taken together, this study reports a new type of antiviral agent and provides a promising pharmaceutical agent for treating infection by the highly pathogenic PRRSV. Moreover, it may provide novel ideas for the research and development of antiviral formulations based on nanocomposites and extend their applications in biol. systems.
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97Du, T.; Liang, J.; Dong, N.; Liu, L.; Fang, L.; Xiao, S.; Han, H. Carbon Dots as Inhibitors of Virus by Activation of Type I Interferon Response. Carbon 2016, 110, 278– 285, DOI: 10.1016/j.carbon.2016.09.032Google Scholar97https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhsFCmtLnF&md5=8807c9a8abb01c40df79ba928e03ae97Carbon dots as inhibitors of virus by activation of type I interferon responseDu, Ting; Liang, Jiangong; Dong, Nan; Liu, Lin; Fang, Liurong; Xiao, Shaobo; Han, HeyouCarbon (2016), 110 (), 278-285CODEN: CRBNAH; ISSN:0008-6223. (Elsevier Ltd.)Carbon dots (CDs) has shown exciting potential in the field of bioscience and biotechnol. due to their low toxicity, biol. and ecol. friendliness and desirable performance characteristics of quantum dots (QDs). However, the effects of CDs on viruses are still largely unknown. In this study, we investigate the effect of CDs on the replication of virus by using pseudorabies virus (PRV) and porcine reproductive and respiratory syndrome virus (PRRSV) as the models of DNA virus and RNA virus, resp. Analyses of virus titers and the expression of viral proteins demonstrate that cells treated with CDs can significantly inhibit the multiplication of PRV and PRRSV. In mechanism, CDs treatment dramatically induces interferon-α (IFN-α) prodn. and the expression of IFN-stimulating genes (ISGs) which in turn inhibits virus replication. Taken together, these results reveal a previously undefined role of CDs and provide a new strategy to develop antiviral agents.
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98Sharma, V.; Kaushik, S.; Pandit, P.; Dhull, D.; Yadav, J. P.; Kaushik, S. Green Synthesis of Silver Nanoparticles from Medicinal Plants and Evaluation of Their Antiviral Potential against Chikungunya Virus. Appl. Microbiol. Biotechnol. 2019, 103, 881– 891, DOI: 10.1007/s00253-018-9488-1Google Scholar98https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXitFOjt7jL&md5=799fec3583ceb89e334815ce4d6859dcGreen synthesis of silver nanoparticles from medicinal plants and evaluation of their antiviral potential against chikungunya virusSharma, Vikrant; Kaushik, Sulochana; Pandit, Pooja; Dhull, Divya; Yadav, Jaya Parkash; Kaushik, SamanderApplied Microbiology and Biotechnology (2019), 103 (2), 881-891CODEN: AMBIDG; ISSN:0175-7598. (Springer)The exploration of nanoscale materials for their therapeutic potential against emerging and re-emerging infections has been increased in recent years. Silver nanoparticles (AgNPs) are known to possess antimicrobial activities against different pathogens including viruses and provide an excellent opportunity to develop new antivirals. The present study focused on biol. synthesis of AgNPs from Andrographis paniculata, Phyllanthus niruri, and Tinospora cordifolia and evaluation of their antiviral properties against chikungunya virus. Synthesized plants AgNPs were characterized to assess their formation, morphol., and stability. The cytotoxicity assays in Vero cells revealed that A. paniculata AgNPs were most cytotoxic with max. non-toxic dose (MNTD) value of 31.25μg/mL followed by P. niruri (MNTD, 125μg/mL) and T. cordifolia AgNPs (MNTD, 250μg/mL). In vitro antiviral assay of AgNPs based on degree of inhibition of cytopathic effect (CPE) showed that A. paniculata AgNPs were most effective, followed by T. cordifolia and P. niruri AgNPs. The results of antiviral assay were confirmed by cell viability test using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) dye, which revealed that A. paniculata AgNPs inhibited the virus to a max. extent. The cell viability of CHIKV-infected cells significantly increased from 25.69% to 80.76 and 66.8%, when treated with A. paniculata AgNPs at MNTD and 1/2MNTD, resp. These results indicated that use of plants AgNPs as antiviral agents is feasible and could provide alternative treatment options against viral diseases which have no specific antiviral or vaccines available yet.
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99Yang, X. X.; Li, C. M.; Huang, C. Z. Curcumin Modified Silver Nanoparticles for Highly Efficient Inhibition of Respiratory Syncytial Virus Infection. Nanoscale 2016, 8, 3040– 3048, DOI: 10.1039/C5NR07918GGoogle Scholar99https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XislKnsw%253D%253D&md5=8a288a70879432df568881c84b1d6046Curcumin modified silver nanoparticles for highly efficient inhibition of respiratory syncytial virus infectionYang, Xiao Xi; Li, Chun Mei; Huang, Cheng ZhiNanoscale (2016), 8 (5), 3040-3048CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)Interactions between nanoparticles and viruses have attracted increasing attention due to the antiviral activity of nanoparticles and the resulting possibility to be employed as biomedical interventions. In this contribution, we developed a very simple route to prep. uniform and stable silver nanoparticles (AgNPs) with antiviral properties by using curcumin, which is a member of the ginger family isolated from rhizomes of the perennial herb Curcuma longa and has a wide range of biol. activities like antioxidant, antifungal, antibacterial and anti-inflammatory effects, and acts as reducing and capping agents in this synthetic route. The tissue culture infectious dose (TCID50) assay showed that the curcumin modified silver nanoparticles (cAgNPs) have a highly efficient inhibition effect against respiratory syncytial virus (RSV) infection, giving a decrease of viral titers about two orders of magnitude at the concn. of cAgNPs under which no toxicity was found to the host cells. Mechanism investigations showed that cAgNPs could prevent RSV from infecting the host cells by inactivating the virus directly, indicating that cAgNPs are a novel promising efficient virucide for RSV.
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100Elechiguerra, J. L.; Burt, J. L.; Morones, J. R.; Camacho-Bragado, A.; Gao, X.; Lara, H. H.; Yacaman, M. J. Interaction of Silver Nanoparticles with HIV-1. J. Nanobiotechnol. 2005, 3, 6, DOI: 10.1186/1477-3155-3-6Google Scholar100https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD2MvltlGquw%253D%253D&md5=5489a919aa800a88e7dce2398d029494Interaction of silver nanoparticles with HIV-1Elechiguerra Jose Luis; Burt Justin L; Morones Jose R; Camacho-Bragado Alejandra; Gao Xiaoxia; Lara Humberto H; Yacaman Miguel JoseJournal of nanobiotechnology (2005), 3 (), 6 ISSN:.The interaction of nanoparticles with biomolecules and microorganisms is an expanding field of research. Within this field, an area that has been largely unexplored is the interaction of metal nanoparticles with viruses. In this work, we demonstrate that silver nanoparticles undergo a size-dependent interaction with HIV-1, with nanoparticles exclusively in the range of 1-10 nm attached to the virus. The regular spatial arrangement of the attached nanoparticles, the center-to-center distance between nanoparticles, and the fact that the exposed sulfur-bearing residues of the glycoprotein knobs would be attractive sites for nanoparticle interaction suggest that silver nanoparticles interact with the HIV-1 virus via preferential binding to the gp120 glycoprotein knobs. Due to this interaction, silver nanoparticles inhibit the virus from binding to host cells, as demonstrated in vitro.
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101Bowman, M.-C.; Ballard, T. E.; Ackerson, C. J.; Feldheim, D. L.; Margolis, D. M.; Melander, C. Inhibition of HIV Fusion with Multivalent Gold Nanoparticles. J. Am. Chem. Soc. 2008, 130, 6896– 6897, DOI: 10.1021/ja710321gGoogle Scholar101https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXlvFyrsr8%253D&md5=6defba3d410e679b11f1ee75efd8dda6Inhibition of HIV Fusion with Multivalent Gold NanoparticlesBowman, Mary-Catherine; Ballard, T. Eric; Ackerson, Christopher J.; Feldheim, Daniel L.; Margolis, David M.; Melander, ChristianJournal of the American Chemical Society (2008), 130 (22), 6896-6897CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)The design and synthesis of a multivalent gold nanoparticle therapeutic is presented. SDC-1721, a fragment of the potent HIV inhibitor TAK-779, was synthesized and conjugated to 2.0 nm diam. gold nanoparticles. Free SDC-1721 had no inhibitory effect on HIV infection; however, the (SDC-1721)-gold nanoparticle conjugates displayed activity comparable to that of TAK-779. This result suggests that multivalent presentation of small mols. on gold nanoparticle surfaces can convert inactive drugs into potent therapeutics.
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102Di Gianvincenzo, P.; Marradi, M.; Martínez-Ávila, O. M.; Bedoya, L. M.; Alcamí, J.; Penadés, S. Gold Nanoparticles Capped with Sulfate-Ended Ligands as Anti-HIV Agents. Bioorg. Med. Chem. Lett. 2010, 20, 2718– 2721, DOI: 10.1016/j.bmcl.2010.03.079Google Scholar102https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXkvFeqtbc%253D&md5=139966eefbcd5f9a04e36e83e0018aa1Gold nanoparticles capped with sulfate-ended ligands as anti-HIV agentsDi Gianvincenzo, Paolo; Marradi, Marco; Martinez-Avila, Olga Maria; Bedoya, Luis Miguel; Alcami, Jose; Penades, SoledadBioorganic & Medicinal Chemistry Letters (2010), 20 (9), 2718-2721CODEN: BMCLE8; ISSN:0960-894X. (Elsevier B.V.)Gold nanoparticles coated with multiple copies of an amphiphilic sulfate-ended ligand are able to bind the HIV envelope glycoprotein gp120 as measured by surface plasmon resonance (SPR) and inhibit in vitro the HIV infection of T-cells at nanomolar concns. A 50% d. of sulfated ligands on ∼2 nm nanoparticles (the other ligands being inert glucose derivs.) is enough to achieve high anti-HIV activities. This result opens up the possibility of tailoring both sulfated ligands and other anti-HIV mols. on the same gold cluster, thus contributing to the development of non-cocktail based multifunctional anti-HIV systems.
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103Rosemary Bastian, A.; Nangarlia, A.; Bailey, L. D.; Holmes, A.; Kalyana Sundaram, R. V.; Ang, C.; Moreira, D. R.; Freedman, K.; Duffy, C.; Contarino, M.; Abrams, C.; Root, M.; Chaiken, I. Mechanism of Multivalent Nanoparticle Encounter with HIV-1 for Potency Enhancement of Peptide Triazole Virus Inactivation. J. Biol. Chem. 2015, 290, 529– 543, DOI: 10.1074/jbc.M114.608315Google Scholar103https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2M3lslekug%253D%253D&md5=7052ac7786204d8e6328c83a8edc5b4cMechanism of multivalent nanoparticle encounter with HIV-1 for potency enhancement of peptide triazole virus inactivationRosemary Bastian Arangassery; Nangarlia Aakansha; Kalyana Sundaram R Venkat; Ang Charles; Bailey Lauren D; Holmes Andrew; Duffy Caitlin; Contarino Mark; Chaiken Irwin; Moreira Diogo R M; Freedman Kevin; Abrams Cameron; Root MichaelThe Journal of biological chemistry (2015), 290 (1), 529-43 ISSN:.Entry of HIV-1 into host cells remains a compelling yet elusive target for developing agents to prevent infection. A peptide triazole (PT) class of entry inhibitor has previously been shown to bind to HIV-1 gp120, suppress interactions of the Env protein at host cell receptor binding sites, inhibit cell infection, and cause envelope spike protein breakdown, including gp120 shedding and, for some variants, virus membrane lysis. We found that gold nanoparticle-conjugated forms of peptide triazoles (AuNP-PT) exhibit substantially more potent antiviral effects against HIV-1 than corresponding peptide triazoles alone. Here, we sought to reveal the mechanism of potency enhancement underlying nanoparticle conjugate function. We found that altering the physical properties of the nanoparticle conjugate, by increasing the AuNP diameter and/or the density of PT conjugated on the AuNP surface, enhanced potency of infection inhibition to impressive picomolar levels. Further, compared with unconjugated PT, AuNP-PT was less susceptible to reduction of antiviral potency when the density of PT-competent Env spikes on the virus was reduced by incorporating a peptide-resistant mutant gp120. We conclude that potency enhancement of virolytic activity and corresponding irreversible HIV-1 inactivation of PTs upon AuNP conjugation derives from multivalent contact between the nanoconjugates and metastable Env spikes on the HIV-1 virus. The findings reveal that multispike engagement can exploit the metastability built into virus the envelope to irreversibly inactivate HIV-1 and provide a conceptual platform to design nanoparticle-based antiviral agents for HIV-1 specifically and putatively for metastable enveloped viruses generally.
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104Speshock, J. L.; Murdock, R. C.; Braydich-Stolle, L. K.; Schrand, A. M.; Hussain, S. M. Interaction of Silver Nanoparticles with Tacaribe Virus. J. Nanobiotechnol. 2010, 8, 19, DOI: 10.1186/1477-3155-8-19Google Scholar104https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3cfhtF2htA%253D%253D&md5=32de5304b6d4301b44174cfb5432a313Interaction of silver nanoparticles with Tacaribe virusSpeshock Janice L; Murdock Richard C; Braydich-Stolle Laura K; Schrand Amanda M; Hussain Saber MJournal of nanobiotechnology (2010), 8 (), 19 ISSN:.BACKGROUND: Silver nanoparticles possess many unique properties that make them attractive for use in biological applications. Recently they received attention when it was shown that 10 nm silver nanoparticles were bactericidal, which is promising in light of the growing number of antibiotic resistant bacteria. An area that has been largely unexplored is the interaction of nanomaterials with viruses and the possible use of silver nanoparticles as an antiviral agent. RESULTS: This research focuses on evaluating the interaction of silver nanoparticles with a New World arenavirus, Tacaribe virus, to determine if they influence viral replication. Surprisingly exposing the virus to silver nanoparticles prior to infection actually facilitated virus uptake into the host cells, but the silver-treated virus had a significant reduction in viral RNA production and progeny virus release, which indicates that silver nanoparticles are capable of inhibiting arenavirus infection in vitro. The inhibition of viral replication must occur during early replication since although pre-infection treatment with silver nanoparticles is very effective, the post-infection addition of silver nanoparticles is only effective if administered within the first 2-4 hours of virus replication. CONCLUSIONS: Silver nanoparticles are capable of inhibiting a prototype arenavirus at non-toxic concentrations and effectively inhibit arenavirus replication when administered prior to viral infection or early after initial virus exposure. This suggests that the mode of action of viral neutralization by silver nanoparticles occurs during the early phases of viral replication.
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105Baram-Pinto, D.; Shukla, S.; Perkas, N.; Gedanken, A.; Sarid, R. Inhibition of Herpes Simplex Virus Type 1 Infection by Silver Nanoparticles Capped with Mercaptoethane Sulfonate. Bioconjugate Chem. 2009, 20, 1497– 1502, DOI: 10.1021/bc900215bGoogle Scholar105https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXot1Gnu78%253D&md5=c170aebd3c6b0924eee7a26b1a8746c8Inhibition of Herpes Simplex Virus Type 1 Infection by Silver Nanoparticles Capped with Mercaptoethane SulfonateBaram-Pinto, Dana; Shukla, Sourabh; Perkas, Nina; Gedanken, Aharon; Sarid, RonitBioconjugate Chemistry (2009), 20 (8), 1497-1502CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)Interactions between biomols. and nanoparticles suggest the use of nanoparticles for various medical interventions. The attachment and entry of herpes simplex virus type 1 (HSV-1) into cells involve interaction between viral envelope glycoproteins and cell surface heparan sulfate (HS). Based on this mechanism, we designed silver nanoparticles that are capped with mercaptoethane sulfonate (Ag-MES). These nanoparticles are predicted to target the virus and to compete for its binding to cellular HS through their sulfonate end groups, leading to the blockage of viral entry into the cell and to the prevention of subsequent infection. Structurally defined Ag-MES nanoparticles that are readily redispersible in water were sonochem. synthesized. No toxic effects of these nanoparticles on host cells were obsd. Effective inhibition of HSV-1 infection in cell culture by the capped nanoparticles was demonstrated. However, application of the sol. surfactant MES failed to inhibit viral infection, implying that the antiviral effect of Ag-MES nanoparticles is imparted by their multivalent nature and spatially directed MES on the surface. Our results suggest that capped nanoparticles may serve as useful topical agents for the prevention of infections with pathogens dependent on HS for entry.
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106Orłowski, P.; Kowalczyk, A.; Tomaszewska, E.; Ranoszek-Soliwoda, K.; Wȩgrzyn, A.; Grzesiak, J.; Celichowski, G.; Grobelny, J.; Eriksson, K.; Krzyzowska, M. Antiviral Activity of Tannic Acid Modified Silver Nanoparticles: Potential to Activate Immune Response in Herpes Genitalis. Viruses 2018, 10, 524, DOI: 10.3390/v10100524Google Scholar106https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXmvFGrs7Y%253D&md5=5f5438b29ec978984cc3c85ac343a8d1Antiviral activity of tannic acid modified silver nanoparticles: potential to activate immune response in herpes genitalisOrlowski, Piotr; Kowalczyk, Andrzej; Tomaszewska, Emilia; Ranoszek-Soliwoda, Katarzyna; W, egrzyn, Agnieszka; Grzesiak, Jakub; Celichowski, Grzegorz; Grobelny, Jaroslaw; Eriksson, Kristina; Krzyzowska, MalgorzataViruses (2018), 10 (10), 524/1-524/15CODEN: VIRUBR; ISSN:1999-4915. (MDPI AG)Tannic acid is a plant-derived polyphenol showing antiviral activity mainly because of an interference with the viral adsorption. In this work, we tested whether the modification of silver nanoparticles with tannic acid (TA-AgNPs) can provide a microbicide with addnl. adjuvant properties to treat genital herpes infection. The mouse model of the vaginal herpes simplex virus 2 (HSV-2) infection was used to test immune responses after treatment of the primary infection with TA-AgNPs, and later, after a re-challenge with the virus. The mice treated intravaginally with TA-AgNPs showed better clin. scores and lower virus titers in the vaginal tissues soon after treatment. Following a re-challenge, the vaginal tissues treated with TA-AgNPs showed a significant increase in the percentages of IFN-gamma+ CD8+ T-cells, activated B cells, and plasma cells, while the spleens contained significantly higher percentages of IFN-gamma+ NK cells and effector-memory CD8+ T cells in comparison to NaCl-treated group. TA-AgNPs-treated animals also showed significantly better titers of anti-HSV-2 neutralization antibodies in sera; and. Our findings suggest that TA-AgNPs sized 33 nm can be an effective anti-viral microbicide to be applied upon the mucosal tissues with addnl. adjuvant properties enhancing an anti-HSV-2 immune response following secondary challenge.
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107Gaikwad, S.; Ingle, A.; Gade, A.; Rai, M.; Falanga, A.; Incoronato, N.; Russo, L.; Galdiero, S.; Galdiero, M. Antiviral Activity of Mycosynthesized Silver Nanoparticles against Herpes Simplex Virus and Human Parainfluenza Virus Type 3. Int. J. Nanomed. 2013, 8, 4303– 4314, DOI: 10.2147/IJN.S50070Google ScholarThere is no corresponding record for this reference.
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108Qin, T.; Ma, R.; Yin, Y.; Miao, X.; Chen, S.; Fan, K.; Xi, J.; Liu, Q.; Gu, Y.; Yin, Y.; Hu, J.; Liu, X.; Peng, D.; Gao, L. Catalytic Inactivation of Influenza Virus by Iron Oxide Nanozyme. Theranostics 2019, 9, 6920– 6935, DOI: 10.7150/thno.35826Google Scholar108https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXps1GjurY%253D&md5=c68a1e8e211cb41e8cf7f02b122d7ac8Catalytic inactivation of influenza virus by iron oxide nanozymeQin, Tao; Ma, Ruonan; Yin, Yinyan; Miao, Xinyu; Chen, Sujuan; Fan, Kelong; Xi, Juqun; Liu, Qi; Gu, Yunhao; Yin, Yuncong; Hu, Jiao; Liu, Xiufan; Peng, Daxin; Gao, LizengTheranostics (2019), 9 (23), 6920-6935CODEN: THERDS; ISSN:1838-7640. (Ivyspring International Publisher)Influenza poses a severe threat to human health in the world. However, developing a universal anti-viral strategy has remained challenging due to the presence of diverse subtypes as well as its high mutation rate, resulting in antigenic shift and drift. Here we developed an antiviral strategy using iron oxide nanozymes (IONzymes) to target the lipid envelope of the influenza virus. Methods: We evaluated the antiviral activities of our IONzymes using a hemagglutination assay, together with a 50% tissue culture infectious doses (TCID50) method. Lipid peroxidn. of the viral envelope was analyzed using a maleic dialdehyde (MDA) assay and transmission electron microscopy (TEM). The neighboring viral proteins were detected by western blotting. Results: We show that IONzymes induce envelope lipid peroxidn. and destroy the integrity of neighboring proteins, including hemagglutinin, neuraminidase, and matrix protein 1, causing the inactivation of influenza A viruses (IAVs). Furthermore, we show that our IONzymes possess a broad-spectrum antiviral activity on 12 subtypes of IAVs (H1~ H12). Lastly, we demonstrate that applying IONzymes to a facemask improves the ability of virus protection against 3 important subtypes that pose a threat to human, including H1N1, H5N1, and H7N9 subtype. Conclusion: Together, our results clearly demonstrate that IONzymes can catalyze lipid peroxidn. of the viral lipid envelope to inactivate enveloped viruses and provide protection from viral transmission and infection.
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109Lim, M. E.; Lee, Y. L.; Zhang, Y.; Chu, J. J. Photodynamic Inactivation of Viruses Using Upconversion Nanoparticles. Biomaterials 2012, 33, 1912– 1920, DOI: 10.1016/j.biomaterials.2011.11.033Google Scholar109https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhs1ejtLzI&md5=a1bff591872b481e1da97c1a0f5213e9Photodynamic inactivation of viruses using upconversion nanoparticlesLim, Meng Earn; Lee, Yen-ling; Zhang, Yong; Chu, Justin Jang HannBiomaterials (2012), 33 (6), 1912-1920CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)Photodynamic therapy (PDT) is a promising treatment modality that utilizes light of an appropriate wavelength to excite photosensitive materials called photosensitizers, which upon excitation, generate reactive oxygen species (ROS) that are cytocidal and virucidal. However, problems such as hydrophobicity of photosensitizers and limited tissue penetration ability of the current light sources impeded its promotion as a mainstay in medical technol. Here, by using near-IR (NIR)-to-visible upconversion nanoparticles (UCNs), we demonstrate UCN-based photodynamic inactivation as a potential antiviral strategy. These UCNs are nanotransducers which not only act as carriers of photosensitizers but also active participants in PDT by transducing NIR radiation to visible emissions appropriate for excitation of the attached photosensitizers. The UCNs effectively reduced the infectious virus titers in vitro with no clear pathogenicity in murine model and increased target specificity to virus-infected cells. Hence, this is a promising antiviral approach with feasible applications in the treatments of virus-assocd. infections, lesions and cancers.
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110Meléndez-Villanueva, M. A.; Morán-Santibañez, K.; Martínez-Sanmiguel, J. J.; Rangel-López, R.; Garza-Navarro, M. A.; Rodríguez-Padilla, C.; Zarate-Triviño, D. G.; Trejo-Ávila, L. M. Virucidal Activity of Gold Nanoparticles Synthesized by Green Chemistry Using Garlic Extract. Viruses 2019, 11, 1111, DOI: 10.3390/v11121111Google Scholar110https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXmsVGku7o%253D&md5=04385cea5d4f4f1e7245f3965af92c4aVirucidal activity of gold nanoparticles synthesized by green chemistry using garlic extractMelendez-Villanueva, Mayra A.; Moran-Santibanez, Karla; Martinez-Sanmiguel, Juan J.; Rangel-Lopez, Raul; Garza-Navarro, Marco A.; Rodriguez-Padilla, Cristina; Zarate-Trivino, Diana G.; Trejo-Avila, Laura M.Viruses (2019), 11 (12), 1111CODEN: VIRUBR; ISSN:1999-4915. (MDPI AG)Measles virus (MeV) is a paramyxovirus that infects humans, principally children. Despite the existence of an effective and safe vaccine, the no. of cases of measles has increased due to lack of vaccination coverage. The World Health Organization (WHO) reports that the no. of cases worldwide multiplied fourfold between Jan. and March 2019, to 112,000. Today, there is no treatment available for MeV. In recent years, it has been demonstrated that natural exts. (herbal or algal) with antiviral activity can also work as reducing agents that, in combination with nanotechnol., offer an innovative option to counteract viral infections. Here, we synthesized and evaluated the antiviral activity of gold nanoparticles using garlic ext. (Allium sativa) as a reducing agent (AuNPs-As). These nanoparticles actively inhibited MeV replication in Vero cells at a 50% effective concn. (EC50) of 8.829 μg/mL, and the selectivity index (SI) obtained was 16.05. AuNPs-As likely inhibit viral infection by blocking viral particles directly, showing a potent virucidal effect. Gold nanoparticles may be useful as a promising strategy for treating and controlling the infection of MeV and other related enveloped viruses.
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111Wang, Z.; Liu, H.; Yang, S. H.; Wang, T.; Liu, C.; Cao, Y. C. Nanoparticle-Based Artificial RNA Silencing Machinery for Antiviral Therapy. Proc. Natl. Acad. Sci. U. S. A. 2012, 109, 12387– 12392, DOI: 10.1073/pnas.1207766109Google Scholar111https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtleqsrjF&md5=486acf5ec619e96a368f1537796f5906Nanoparticle-based artificial RNA silencing machinery for antiviral therapyWang, Zhongliang; Liu, Hongyan; Yang, Soon Hye; Wang, Tie; Liu, Chen; Cao, Y. CharlesProceedings of the National Academy of Sciences of the United States of America (2012), 109 (31), 12387-12392, S12387/1-S12387/7CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)RNA interference is a fundamental gene regulatory mechanism that is mediated by the RNA-induced silencing complex (RISC). Here we report that an artificial nanoparticle complex can effectively mimic the function of the cellular RISC machinery for inducing target RNA cleavage. Our results show that a specifically designed nanozyme for the treatment of hepatitis C virus (HCV) can actively cleave HCV RNA in a sequence specific manner. This nanozyme is less susceptible to degrdn. by proteinase activity, can be effectively taken up by cultured human hepatoma cells, is nontoxic to the cultured cells and a xenotransplantation mouse model under the conditions studied, and does not trigger detectable cellular interferon response, but shows potent antiviral activity against HCV in cultured cells and in the mouse model. We have obsd. a more than 99% decrease in HCV RNA levels in mice treated with the nanozyme. These results show that this nanozyme approach has the potential to become a useful tool for functional genomics, as well as for combating protein-expression-related diseases such as viral infections and cancers.
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112Park, S.; Ko, Y. S.; Lee, S. J.; Lee, C.; Woo, K.; Ko, G. Inactivation of Influenza a Virus Via Exposure to Silver Nanoparticle-Decorated Silica Hybrid Composites. Environ. Sci. Pollut. Res. 2018, 25, 27021– 27030, DOI: 10.1007/s11356-018-2620-zGoogle Scholar112https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhtlGlsb%252FO&md5=54b7670a25dc289c763cd6e9848c692aInactivation of influenza A virus via exposure to silver nanoparticle-decorated silica hybrid compositesPark, SungJun; Ko, Young-Seon; Lee, Su Jin; Lee, Cheonghoon; Woo, Kyoungja; Ko, GwangPyoEnvironmental Science and Pollution Research (2018), 25 (27), 27021-27030CODEN: ESPLEC; ISSN:0944-1344. (Springer)Influenza A virus (IFV-A) is one of the main cause of seasonal flu and can infect various of host species via the reassortment of segmented RNA genomes. Silver nanoparticles (AgNPs) have been known as excellent antiviral agent against IFV. However, the use of free AgNPs has several major drawbacks, including the inherent aggregation among AgNPs and unwanted cytotoxic or genotoxic damages for human body via inhalation or ingestion. In this study, we assessed the efficacy of our novel ∼ 30-nm-diam. AgNP-decorated silica hybrid composite (Ag30-SiO2; ∼ 400 nm in diam.) for IFV-A inactivation. Ag30-SiO2 particles can inhibit IFV-A effectively in a clear dose-dependent manner. However, when real-time RT-PCR assay was used, merely 0.5-log10 redn. of IFV-A was obsd. at both 5 and 20°C. Moreover, even after 1 h of exposure to Ag30-SiO2 particles, more than 80% of hemagglutinin (HA) damage and 20% of neuraminidase (NA) activities had occurred, and the infection of Madin-Darby Canine Kidney (MDCK) cells by IFV-A was reduced. The results suggested that the major antiviral mechanism of Ag30-SiO2 particles is the interaction with viral components located at the membrane. Therefore, Ag30-SiO2 particles can cause nonspecific damage to various IFV-A components and be used as an effective method for inactivating IFV-A.
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113Botequim, D.; Maia, J.; Lino, M. M. F.; Lopes, L. M. F.; Simões, P. N.; Ilharco, L. M.; Ferreira, L. Nanoparticles and Surfaces Presenting Antifungal, Antibacterial and Antiviral Properties. Langmuir 2012, 28, 7646– 7656, DOI: 10.1021/la300948nGoogle Scholar113https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XmtlCrsrc%253D&md5=83f50bdd9b57eadc56e72a02f1698d21Nanoparticles and Surfaces Presenting Antifungal, Antibacterial and Antiviral PropertiesBotequim, D.; Maia, J.; Lino, M. M. F.; Lopes, L. M. F.; Simoes, P. N.; Ilharco, L. M.; Ferreira, L.Langmuir (2012), 28 (20), 7646-7656CODEN: LANGD5; ISSN:0743-7463. (American Chemical Society)Here, we present new antimicrobial nanoparticles based on silica nanoparticles (SNPs) coated with a quaternary ammonium cationic surfactant, didodecyldimethylammonium bromide (DDAB). Depending on the initial concn. of DDAB, SNPs immobilize between 45 and 275 μg of DDAB per mg of nanoparticle. For high concns. of DDAB adsorbed to SNP, a bilayer is formed as confirmed by zeta potential measurements, thermogravimetry, and diffuse reflectance IR Fourier transform (DRIFT) analyses. Interestingly, these nanoparticles have lower minimal inhibitory concns. (MIC) against bacteria and fungi than sol. surfactant. The electrostatic interaction of the DDAB with the SNP is strong, since no measurable loss of antimicrobial activity was obsd. after suspension in aq. soln. for 60 days. We further show that the antimicrobial activity of the nanoparticle does not require the leaching of the surfactant from the surface of the NPs. The SNPs may be immobilized onto surfaces with different chem. while maintaining their antimicrobial activity, in this case extended to a virucidal activity. The versatility, relative facility in prepn., low cost, and large antimicrobial activity of our platform makes it attractive as a coating for large surfaces.
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114Lara, H. H.; Ayala-Nuñez, N. V.; Ixtepan-Turrent, L.; Rodriguez-Padilla, C. Mode of Antiviral Action of Silver Nanoparticles against HIV-1. J. Nanobiotechnol. 2010, 8, 1, DOI: 10.1186/1477-3155-8-1Google Scholar114https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3c%252FpslertQ%253D%253D&md5=41c3f4b3c6c9d2bbe683745cc677830dMode of antiviral action of silver nanoparticles against HIV-1Lara Humberto H; Ayala-Nunez Nilda V; Ixtepan-Turrent Liliana; Rodriguez-Padilla CristinaJournal of nanobiotechnology (2010), 8 (), 1 ISSN:.BACKGROUND: Silver nanoparticles have proven to exert antiviral activity against HIV-1 at non-cytotoxic concentrations, but the mechanism underlying their HIV-inhibitory activity has not been not fully elucidated. In this study, silver nanoparticles are evaluated to elucidate their mode of antiviral action against HIV-1 using a panel of different in vitro assays. RESULTS: Our data suggest that silver nanoparticles exert anti-HIV activity at an early stage of viral replication, most likely as a virucidal agent or as an inhibitor of viral entry. Silver nanoparticles bind to gp120 in a manner that prevents CD4-dependent virion binding, fusion, and infectivity, acting as an effective virucidal agent against cell-free virus (laboratory strains, clinical isolates, T and M tropic strains, and resistant strains) and cell-associated virus. Besides, silver nanoparticles inhibit post-entry stages of the HIV-1 life cycle. CONCLUSIONS: These properties make them a broad-spectrum agent not prone to inducing resistance that could be used preventively against a wide variety of circulating HIV-1 strains.
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115Wei, X.; Zhang, G.; Ran, D.; Krishnan, N.; Fang, R. H.; Gao, W.; Spector, S. A.; Zhang, L. T-Cell-Mimicking Nanoparticles Can Neutralize HIV Infectivity. Adv. Mater. 2018, 30, 1802233, DOI: 10.1002/adma.201802233Google ScholarThere is no corresponding record for this reference.
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116Bai, Y.; Zhou, Y.; Liu, H.; Fang, L.; Liang, J.; Xiao, S. Glutathione-Stabilized Fluorescent Gold Nanoclusters Vary in Their Influences on the Proliferation of Pseudorabies Virus and Porcine Reproductive and Respiratory Syndrome Virus. ACS Appl. Nano Mater. 2018, 1, 969– 976, DOI: 10.1021/acsanm.7b00386Google Scholar116https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhsl2jsbs%253D&md5=64430c2280999058678ccf45c71c6660Glutathione-Stabilized Fluorescent Gold Nanoclusters Vary in Their Influences on the Proliferation of Pseudorabies Virus and Porcine Reproductive and Respiratory Syndrome VirusBai, Yanli; Zhou, Yanrong; Liu, Huabing; Fang, Liurong; Liang, Jiangong; Xiao, ShaoboACS Applied Nano Materials (2018), 1 (2), 969-976CODEN: AANMF6; ISSN:2574-0970. (American Chemical Society)Gold nanoclusters (Au NCs) are widely used in biol. imaging and antitumor treatment because of their excellent cell membrane permeability, good fluorescence properties, and high biocompatibility. However, their effects on viruses are still largely unknown. Here, pseudorabies virus (PRV) and porcine reproductive and respiratory syndrome virus (PRRSV) were used resp. as the models of DNA virus and RNA virus to investigate the influences of glutathione-stabilized fluorescent Au NCs on viruses by plaque assay, indirect immunofluorescence assay, quant. real-time polymerase chain reaction assay, and Western blot assay. The exptl. data indicated that Au NCs selectively inhibited proliferation and protein expression of PRRSV but not that of PRV. Mechanistically, Au NCs directly inactivated PRRSV and blocked viral adsorption but showed no effect on viral genome replication. These findings prompt the possibility of developing Au NCs as an effective specific antiviral nanomaterial against RNA virus infection in the future.
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117Zhang, J.-M.; An, J. Cytokines, Inflammation, and Pain. Int. Anesthesiol. Clin. 2007, 45, 27– 37, DOI: 10.1097/AIA.0b013e318034194eGoogle Scholar117https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD2s3msF2ltg%253D%253D&md5=24aae56f3283e4a330226c914fd846bcCytokines, inflammation, and painZhang Jun-Ming; An JianxiongInternational anesthesiology clinics (2007), 45 (2), 27-37 ISSN:0020-5907.There is no expanded citation for this reference.
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118Lung, P.; Yang, J.; Li, Q. Nanoparticle Formulated Vaccines: Opportunities and Challenges. Nanoscale 2020, 12, 5746– 5763, DOI: 10.1039/C9NR08958FGoogle Scholar118https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXktFWgsbw%253D&md5=65a2fc077008f9fa9d0ac85352a50c29Nanoparticle formulated vaccines: opportunities and challengesLung, Pingsai; Yang, Jingnan; Li, QuanNanoscale (2020), 12 (10), 5746-5763CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)Vaccines harness the inherent properties of the immune system to prevent diseases or treat existing ones. Continuous efforts have been devoted to both gaining a mechanistic understanding of how the immune system operates and designing vaccines with high efficacies and effectiveness. Advancements in nanotechnol. in recent years have generated unique opportunities to meet the daunting challenges assocd. with immunol. and vaccine development. Firstly, nanoparticle formulated systems provide ideal model systems for studying the operation of the immune system, making it possible to systematically identify key factors and understand their roles in specific immune responses. Also, the versatile compns./architectures of nanoparticle systems enable new strategies/novel platforms for developing vaccines with high efficacies and effectiveness. In this review, we discuss the advantages of nanoparticles and the challenges faced during vaccine development, through the framework of the immunol. mechanisms of vaccination, with the aim of bridging the gap between immunol. and materials science, which are both involved in vaccine design. The knowledge obtained provides general guidelines for future vaccine development.
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119Ramshaw, I. A.; Ramsay, A. J.; Karupiah, G.; Rolph, M. S.; Mahalingam, S.; Ruby, J. C. Cytokines and Immunity to Viral Infections. Immunol. Rev. 1997, 159, 119– 135, DOI: 10.1111/j.1600-065X.1997.tb01011.xGoogle Scholar119https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXnvFKrtLw%253D&md5=b03bef37289586a5a4a899b20b216157Cytokines and immunity to viral infectionsRamshaw, Ian A.; Ramsay, Alistair J.; Karupiah, Gunasegaran; Rolph, Michael S.; Mahalingam, Surendran; Ruby, Janet C.Immunological Reviews (1997), 159 (), 119-135CODEN: IMRED2; ISSN:0105-2896. (Munksgaard International Publishers Ltd.)In this review with 96 refs., the authors discuss 2 broad approaches they have taken to study the role of cytokines and chemokines in antiviral immunity. Firstly, recombinant vaccinia viruses were engineered to express genes encoding cytokines and chemokines of interest. Potent antiviral activity was mediated by many of these encoded factors, including IL-2, IL-12, IFN-γ, TNF-α, CD40L, Mig, and Crg-2. In some cases, host defense mechanisms were induced, while for others, a direct antiviral effect was demonstrated. In sharp contrast, vector-directed expression of IL-4, a type 2 factor, greatly increased virus virulence, due to a downregulation of host type 1 immune responses. The second exptl. approach involved the use of strains of mice deficient for the prodn. of particular cytokines or their receptors, often in combination with the authors' engineered viruses. Mice deficient in either IFN-γ, IFN-γR, IFN-α/βR, TNFRs, CD40, or IL-6 were, in general, highly susceptible to poxvirus infection. Surprisingly, not only the TNFR1, but also the TNFR2, mediated the antiviral effects of TNF-α in vivo, while the antiviral activity obsd. following CD40/CD40L interaction is a newly defined function which may involve apoptosis of infected cells. Through the use of perforin-deficient mice, the authors could demonstrate a requirement for this mol. in the clearance of some viruses, while for others perforin was less important but IFN-γ was essential.
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120Ruby, J.; Bluethmann, H.; Peschon, J. J. Antiviral Activity of Tumor Necrosis Factor (TNF) Is Mediated Via P55 and P75 TNF Receptors. J. Exp. Med. 1997, 186, 1591– 1596, DOI: 10.1084/jem.186.9.1591Google Scholar120https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXntFerurw%253D&md5=fe4957c7083a12ac69aaa5ba5ad58c09Antiviral activity of tumor necrosis factor (TNF) is mediated via p55 and p75 TNF receptorsRuby, Janet; Bluethmann, Horst; Peschon, Jacques J.Journal of Experimental Medicine (1997), 186 (9), 1591-1596CODEN: JEMEAV; ISSN:0022-1007. (Rockefeller University Press)The antiviral nature of tumor necrosis factor (TNF) is generally well accepted. TNF appears to induce multiple antiviral mechanisms, and to synergize with interferon (IFN)-γ in promoting antiviral activities. We infected TNF receptor (TNFR)-deficient mice with the virulent murine pathogen, ectromelia virus (EV), and obsd. that otherwise resistant mice were susceptible to lethal infection. To study the mol. basis of the antiviral action of TNF, mice were infected with a recombinant vaccinia virus encoding murine TNF (VV-HA-TNF). In normal mice, the replication of VV-HA-TNF was highly attenuated. In contrast, mice in which the TNFR type 1 (p55) or the TNFR type 2 (p75) were genetically disrupted showed a moderate defect in their capacity to clear the TNF-encoding virus. The contribution of both TNF receptors to the control of VV-HA-TNF was confirmed by the enhanced replication of VV-HA-TNF in mice deficient for both p55 and p75. These observations were corroborated by infecting TNFR-deficient mice with EV. For both infections, the p55 and p75 TNFRs were necessary to maintain normal levels of resistance. Thus, the antiviral activity of TNF is mediated via both TNFRs in vivo. Furthermore, these studies establish that TNF is an important component of the host response to a natural virus infection.
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121Sekimukai, H.; Iwata-Yoshikawa, N.; Fukushi, S.; Tani, H.; Kataoka, M.; Suzuki, T.; Hasegawa, H.; Niikura, K.; Arai, K.; Nagata, N. Gold Nanoparticle-Adjuvanted S Protein Induces a Strong Antigen-Specific IgG Response against Severe Acute Respiratory Syndrome-Related Coronavirus Infection, but Fails to Induce Protective Antibodies and Limit Eosinophilic Infiltration in Lungs. Microbiol. Immunol. 2020, 64, 33– 51, DOI: 10.1111/1348-0421.12754Google Scholar121https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXitFKhsrvJ&md5=bab1fc4834c5732cb199c12a925b1ecaGold nanoparticle-adjuvanted S protein induces a strong antigen-specific IgG response against severe acute respiratory syndrome-related coronavirus infection, but fails to induce protective antibodies and limit eosinophilic infiltration in lungsSekimukai, Hanako; Iwata-Yoshikawa, Naoko; Fukushi, Shuetsu; Tani, Hideki; Kataoka, Michiyo; Suzuki, Tadaki; Hasegawa, Hideki; Niikura, Kenichi; Arai, Katsuhiko; Nagata, NoriyoMicrobiology and Immunology (2020), 64 (1), 33-51CODEN: MIIMDV; ISSN:0385-5600. (Wiley-Blackwell)The spike (S) protein of coronavirus, which binds to cellular receptors and mediates membrane fusion for cell entry, is a candidate vaccine target for blocking coronavirus infection. However, some animal studies have suggested that inadequate immunization against severe acute respiratory syndrome coronavirus (SARS-CoV) induces a lung eosinophilic immunopathol. upon infection. The present study evaluated two kinds of vaccine adjuvants for use with recombinant S protein: gold nanoparticles (AuNPs), which are expected to function as both an antigen carrier and an adjuvant in immunization; and Toll-like receptor (TLR) agonists, which have previously been shown to be an effective adjuvant in an UV-inactivated SARS-CoV vaccine. All the mice immunized with more than 0.5μg S protein without adjuvant escaped from SARS after infection with mouse-adapted SARS-CoV; however, eosinophilic infiltrations were obsd. in the lungs of almost all the immunized mice. The AuNP-adjuvanted protein induced a strong IgG response but failed to improve vaccine efficacy or to reduce eosinophilic infiltration because of highly allergic inflammatory responses. Whereas similar virus titers were obsd. in the control animals and the animals immunized with S protein with or without AuNPs, Type 1 interferon and pro-inflammatory responses were moderate in the mice treated with S protein with and without AuNPs. On the other hand, the TLR agonist-adjuvanted vaccine induced highly protective antibodies without eosinophilic infiltrations, as well as Th1/17 cytokine responses. The findings of this study will support the development of vaccines against severe pneumonia-assocd. coronaviruses.
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122Chen, H.-W.; Huang, C.-Y.; Lin, S.-Y.; Fang, Z.-S.; Hsu, C.-H.; Lin, J.-C.; Chen, Y.-I.; Yao, B.-Y.; Hu, C. -M. J. Synthetic Virus-Like Particles Prepared Via Protein Corona Formation Enable Effective Vaccination in an Avian Model of Coronavirus Infection. Biomaterials 2016, 106, 111– 118, DOI: 10.1016/j.biomaterials.2016.08.018Google Scholar122https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtlCqsLvN&md5=08e077389dab6a2808eb43fd4939f703Synthetic virus-like particles prepared via protein corona formation enable effective vaccination in an avian model of coronavirus infectionChen, Hui-Wen; Huang, Chen-Yu; Lin, Shu-Yi; Fang, Zih-Syun; Hsu, Chen-Hsuan; Lin, Jung-Chen; Chen, Yuan-I.; Yao, Bing-Yu; Hu, Che-Ming J.Biomaterials (2016), 106 (), 111-118CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)The ongoing battle against current and rising viral infectious threats has prompted increasing effort in the development of vaccine technol. A major thrust in vaccine research focuses on developing formulations with virus-like features towards enhancing antigen presentation and immune processing. Herein, a facile approach to formulate synthetic virus-like particles (sVLPs) is demonstrated by exploiting the phenomenon of protein corona formation induced by the high-energy surfaces of synthetic nanoparticles. Using an avian coronavirus spike protein as a model antigen, sVLPs were prepd. by incubating 100 nm gold nanoparticles in a soln. contg. an optimized concn. of viral proteins. Following removal of free proteins, antigen-laden particles were recovered and showed morphol. semblance to natural viral particles under nanoparticle tracking anal. and transmission electron microscopy. As compared to inoculation with free proteins, vaccination with the sVLPs showed enhanced lymphatic antigen delivery, stronger antibody titers, increased splenic T-cell response, and reduced infection-assocd. symptoms in an avian model of coronavirus infection. Comparison to a com. whole inactivated virus vaccine also showed evidence of superior antiviral protection by the sVLPs. The study demonstrates a simple yet robust method in bridging viral antigens with synthetic nanoparticles for improved vaccine application; it has practical implications in the management of human viral infections as well as in animal agriculture.
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123Coleman, C. M.; Venkataraman, T.; Liu, Y. V.; Glenn, G. M.; Smith, G. E.; Flyer, D. C.; Frieman, M. B. MERS-CoV Spike Nanoparticles Protect Mice from MERS-CoV Infection. Vaccine 2017, 35, 1586– 1589, DOI: 10.1016/j.vaccine.2017.02.012Google Scholar123https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXjt1KmtLY%253D&md5=92ba1c44d18a8f0fa8f27c84b03392a8MERS-CoV spike nanoparticles protect mice from MERS-CoV infectionColeman, Christopher M.; Venkataraman, Thiagarajan; Liu, Ye V.; Glenn, Gregory M.; Smith, Gale E.; Flyer, David C.; Frieman, Matthew B.Vaccine (2017), 35 (12), 1586-1589CODEN: VACCDE; ISSN:0264-410X. (Elsevier Ltd.)The Middle East respiratory syndrome coronavirus (MERS-CoV) was first discovered in late 2012 and has gone on to cause over 1800 infections and 650 deaths. There are currently no approved therapeutics or vaccinations for MERS-CoV. The MERS-CoV spike (S) protein is responsible for receptor binding and virion entry to cells, is immunodominant and induces neutralizing antibodies in vivo, all of which, make the S protein an ideal target for anti-MERS-CoV vaccines. In this study, we demonstrate protection induced by vaccination with a recombinant MERS-CoV S nanoparticle vaccine and Matrix-M1 adjuvant combination in mice. The MERS-CoV S nanoparticle vaccine produced high titer anti-S neutralizing antibody and protected mice from MERS-CoV infection in vivo.
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124Pimentel, T. A. P. F.; Yan, Z.; Jeffers, S. A.; Holmes, K. V.; Hodges, R. S.; Burkhard, P. Peptide Nanoparticles as Novel Immunogens: Design and Analysis of a Prototypic Severe Acute Respiratory Syndrome Vaccine. Chem. Biol. Drug Des. 2009, 73, 53– 61, DOI: 10.1111/j.1747-0285.2008.00746.xGoogle Scholar124https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXptFCnsw%253D%253D&md5=0e37d95d999b6eb71b22f0af593c8a13Peptide nanoparticles as novel immunogens: design and analysis of a prototypic severe acute respiratory syndrome vaccinePimentel, Tais A. P. F.; Yan, Zhe; Jeffers, Scott A.; Holmes, Kathryn V.; Hodges, Robert S.; Burkhard, PeterChemical Biology & Drug Design (2009), 73 (1), 53-61CODEN: CBDDAL; ISSN:1747-0277. (Wiley-Blackwell)Severe acute respiratory syndrome (SARS) is an infectious disease caused by a novel coronavirus that cost nearly 800 lives. While there have been no recent outbreaks of the disease, the threat remains as SARS coronavirus (SARS-CoV) like strains still exist in animal reservoirs. Therefore, the development of a vaccine against SARS is in grave need. Here, the authors have designed and produced a prototypic SARS vaccine: a self-assembling polypeptide nanoparticle that repetitively displays a SARS B-cell epitope from the C-terminal heptad repeat of the virus' spike protein. Biophys. analyses with CD, TEM and dynamic light scattering confirmed the computational design showing α-helcial nanoparticles with sizes of about 25 nm. Immunization expts. with no adjuvants were performed with BALB/c mice. An investigation of the binding properties of the elicited antibodies showed that they were highly conformation specific for the coiled-coil epitope because they specifically recognized the native trimeric conformation of C-terminal heptad repeat region. Consequently, the antisera exhibited neutralization activity in an in vitro infection inhibition assay. The authors conclude that these peptide nanoparticles represent a promising platform for vaccine design, in particular for diseases that are characterized by neutralizing epitopes with coiled-coil conformation such as SARS-CoV or other enveloped viruses.
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125Wang, C.; Zheng, X.; Gai, W.; Wong, G.; Wang, H.; Jin, H.; Feng, N.; Zhao, Y.; Zhang, W.; Li, N.; Zhao, G.; Li, J.; Yan, J.; Gao, Y.; Hu, G.; Yang, S.; Xia, X. Novel Chimeric Virus-Like Particles Vaccine Displaying MERS-CoV Receptor-Binding Domain Induce Specific Humoral and Cellular Immune Response in Mice. Antiviral Res. 2017, 140, 55– 61, DOI: 10.1016/j.antiviral.2016.12.019Google Scholar125https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhsVelsrw%253D&md5=05f1fe4c2e3ee67be7659c56aa490f0fNovel chimeric virus-like particles vaccine displaying MERS-CoV receptor-binding domain induce specific humoral and cellular immune response in miceWang, Chong; Zheng, Xuexing; Gai, Weiwei; Wong, Gary; Wang, Hualei; Jin, Hongli; Feng, Na; Zhao, Yongkun; Zhang, Weijiao; Li, Nan; Zhao, Guoxing; Li, Junfu; Yan, Jinghua; Gao, Yuwei; Hu, Guixue; Yang, Songtao; Xia, XianzhuAntiviral Research (2017), 140 (), 55-61CODEN: ARSRDR; ISSN:0166-3542. (Elsevier B.V.)Middle East respiratory syndrome coronavirus (MERS-CoV) has continued spreading since its emergence in 2012 with a mortality rate of 35.6%, and is a potential pandemic threat. Prophylactics and therapies are urgently needed to address this public health problem. We report here the efficacy of a vaccine consisting of chimeric virus-like particles (VLP) expressing the receptor binding domain (RBD) of MERS-CoV. In this study, a fusion of the canine parvovirus (CPV) VP2 structural protein gene with the RBD of MERS-CoV can self-assemble into chimeric, spherical VLP (sVLP). SVLP retained certain parvovirus characteristics, such as the ability to agglutinate pig erythrocytes, and structural morphol. similar to CPV virions. Immunization with sVLP induced RBD-specific humoral and cellular immune responses in mice. SVLP-specific antisera from these animals were able to prevent pseudotyped MERS-CoV entry into susceptible cells, with neutralizing antibody titers reaching 1:320. IFN-γ, IL-4 and IL-2 secreting cells induced by the RBD were detected in the splenocytes of vaccinated mice by ELISpot. Furthermore, mice inoculated with sVLP or an adjuvanted sVLP vaccine elicited T-helper 1 (Th1) and T-helper 2 (Th2) cell-mediated immunity. Our study demonstrates that sVLP displaying the RBD of MERS-CoV are promising prophylactic candidates against MERS-CoV in a potential outbreak situation.
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126Wiley, J. A.; Richert, L. E.; Swain, S. D.; Harmsen, A.; Barnard, D. L.; Randall, T. D.; Jutila, M.; Douglas, T.; Broomell, C.; Young, M.; Harmsen, A. Inducible Bronchus-Associated Lymphoid Tissue Elicited by a Protein Cage Nanoparticle Enhances Protection in Mice against Diverse Respiratory Viruses. PLoS One 2009, 4, e7142, DOI: 10.1371/journal.pone.0007142Google ScholarThere is no corresponding record for this reference.
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127Lin, L. C. -W.; Huang, C.-Y.; Yao, B.-Y.; Lin, J.-C.; Agrawal, A.; Algaissi, A.; Peng, B.-H.; Liu, Y.-H.; Huang, P.-H.; Juang, R.-H.; Chang, Y.-C.; Tseng, C.-T.; Chen, H.-W.; Hu, C. -M. J. Viromimetic Sting Agonist-Loaded Hollow Polymeric Nanoparticles for Safe and Effective Vaccination against Middle East Respiratory Syndrome Coronavirus. Adv. Funct. Mater. 2019, 29, 1807616, DOI: 10.1002/adfm.201807616Google Scholar127https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB38znsFWmsw%253D%253D&md5=08ea75b08135b931abb937b01c2dddc5Viromimetic STING Agonist-Loaded Hollow Polymeric Nanoparticles for Safe and Effective Vaccination against Middle East Respiratory Syndrome CoronavirusLin Leon Chien-Wei; Yao Bing-Yu; Lin Jung-Chen; Liu Yu-Han; Hu Che-Ming Jack; Huang Chen-Yu; Huang Ping-Han; Chen Hui-Wen; Agrawal Anurodh; Algaissi Abdullah; Tseng Chien-Te; Algaissi Abdullah; Peng Bi-Hung; Juang Rong-Huay; Chang Yuan-Chih; Tseng Chien-TeAdvanced functional materials (2019), 29 (28), 1807616 ISSN:1616-301X.The continued threat of emerging, highly lethal infectious pathogens such as Middle East respiratory syndrome coronavirus (MERS-CoV) calls for the development of novel vaccine technology that offers safe and effective prophylactic measures. Here, a novel nanoparticle vaccine is developed to deliver subunit viral antigens and STING agonists in a virus-like fashion. STING agonists are first encapsulated into capsid-like hollow polymeric nanoparticles, which show multiple favorable attributes, including a pH-responsive release profile, prominent local immune activation, and reduced systemic reactogenicity. Upon subsequent antigen conjugation, the nanoparticles carry morphological semblance to native virions and facilitate codelivery of antigens and STING agonists to draining lymph nodes and immune cells for immune potentiation. Nanoparticle vaccine effectiveness is supported by the elicitation of potent neutralization antibody and antigen-specific T cell responses in mice immunized with a MERS-CoV nanoparticle vaccine candidate. Using a MERS-CoV-permissive transgenic mouse model, it is shown that mice immunized with this nanoparticle-based MERS-CoV vaccine are protected against a lethal challenge of MERS-CoV without triggering undesirable eosinophilic immunopathology. Together, the biocompatible hollow nanoparticle described herein provides an excellent strategy for delivering both subunit vaccine candidates and novel adjuvants, enabling accelerated development of effective and safe vaccines against emerging viral pathogens.
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128Plummer, E. M.; Manchester, M. Viral Nanoparticles and Virus-Like Particles: Platforms for Contemporary Vaccine Design. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 2011, 3, 174– 196, DOI: 10.1002/wnan.119Google Scholar128https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXislCkur8%253D&md5=3afbaf5a8765a7d8ebb05aac7982d5eeViral nanoparticles and virus-like particles: platforms for contemporary vaccine designPlummer, Emily M.; Manchester, MarianneWiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology (2011), 3 (2), 174-196CODEN: WIRNBH; ISSN:1939-0041. (Wiley-Blackwell)A review. Current vaccines that provide protection against infectious diseases have primarily relied on attenuated or inactivated pathogens. Virus-like particles (VLPs), comprised of capsid proteins that can initiate an immune response but do not include the genetic material required for replication, promote immunogenicity and have been developed and approved as vaccines in some cases. In addn., many of these VLPs can be used as mol. platforms for genetic fusion or chem. attachment of heterologous antigenic epitopes. This approach has been shown to provide protective immunity against the foreign epitopes in many cases. A variety of VLPs and virus-based nanoparticles are being developed for use as vaccines and epitope platforms. These particles have the potential to increase efficacy of current vaccines as well as treat diseases for which no effective vaccines are available.
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129Peek, L. J.; Middaugh, C. R.; Berkland, C. Nanotechnology in Vaccine Delivery. Adv. Drug Delivery Rev. 2008, 60, 915– 928, DOI: 10.1016/j.addr.2007.05.017Google Scholar129https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXlslagu7Y%253D&md5=ab9915070bea91ba6b236b11f0d37a68Nanotechnology in vaccine deliveryPeek, Laura J.; Middaugh, C. Russell; Berkland, CoryAdvanced Drug Delivery Reviews (2008), 60 (8), 915-928CODEN: ADDREP; ISSN:0169-409X. (Elsevier B.V.)A review. With very few adjuvants currently being used in marketed human vaccines, a crit. need exists for novel immunopotentiators and delivery vehicles capable of eliciting humoral, cellular and mucosal immunity. Such crucial vaccine components could facilitate the development of novel vaccines for viral and parasitic infections, such as hepatitis, HIV, malaria, cancer, etc. In this review, we discuss clin. trial results for various vaccine adjuvants and delivery vehicles being developed that are approx. nanoscale (< 1000 nm) in size. Humoral immune responses have been obsd. for most adjuvants and delivery platforms while only viral vectors, ISCOMs and Montanide ISA 51 and 720 have shown cytotoxic T cell responses in the clinic. MF59 and MPL have elicited Th1 responses, and virus-like particles, non-degradable nanoparticles and liposomes have also generated cellular immunity. Such vaccine components have also been evaluated for alternative routes of administration with clin. successes reported for intranasal delivery of viral vectors and proteosomes and oral delivery of a VLP vaccine.
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130World Health Organization (WHO). Draft Landscape of COVID-19 Candidate Vaccines, 2020. https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines (accessed Jul 10, 2020).Google ScholarThere is no corresponding record for this reference.
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131Kim, Y.-S.; Son, A.; Kim, J.; Kwon, S. B.; Kim, M. H.; Kim, P.; Kim, J.; Byun, Y. H.; Sung, J.; Lee, J.; Yu, J. E.; Park, C.; Kim, Y.-S.; Cho, N.-H.; Chang, J.; Seong, B. L. Chaperna-Mediated Assembly of Ferritin-Based Middle East Respiratory Syndrome-Coronavirus Nanoparticles. Front. Immunol. 2018, 9, 1093, DOI: 10.3389/fimmu.2018.01093Google Scholar131https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXit1GjsrrE&md5=06d954421c57cd1fbe0b76793b71ebf2Chaperna-mediated assembly of ferritin-based middle east respiratory syndrome-coronavirus nanoparticlesKim, Young-Seok; Son, Ahyun; Kim, Jihoon; Kwon, Soon Bin; Kim, Myung Hee; Kim, Paul; Kim, Jieun; Byun, Young Ho; Sung, Jemin; Lee, Jinhee; Yu, Ji Eun; Park, Chan; Kim, Yeon-Sook; Cho, Nam-Hyuk; Chang, Jun; Seong, Baik L.Frontiers in Immunology (2018), 9 (), 1093/1-1093/20CODEN: FIRMCW; ISSN:1664-3224. (Frontiers Media S.A.)The folding of monomeric antigens and their subsequent assembly into higher ordered structures are crucial for robust and effective prodn. of nanoparticle (NP) vaccines in a timely and reproducible manner. Despite significant advances in in silico design and structure-based assembly, most engineered NPs are refractory to sol. expression and fail to assemble as designed, presenting major challenges in the manufg. process. The failure is due to a lack of understanding of the kinetic pathways and enabling tech. platforms to ensure successful folding of the monomer antigens into regular assemblages. Capitalizing on a novel function of RNA as a mol. chaperone (chaperna: chaperone + RNA), we provide a robust protein-folding vehicle that may be implemented to NP assembly in bacterial hosts. The receptor-binding domain (RBD) of Middle East respiratory syndrome-coronavirus (MERS-CoV) was fused with the RNA-interaction domain (RID) and bacterioferritin, and expressed in Escherichia coli in a sol. form. Site-specific proteolytic removal of the RID prompted the assemblage of monomers into NPs, which was confirmed by electron microscopy and dynamic light scattering. The mutations that affected the RNA binding to RBD significantly increased the sol. aggregation into amorphous structures, reducing the overall yield of NPs of a defined size. This underscored the RNA-antigen interactions during NP assembly. The sera after mouse immunization effectively interfered with the binding of MERS-CoV RBD to the cellular receptor hDPP4. The results suggest that RNA-binding controls the overall kinetic network of the antigen folding pathway in favor of enhanced assemblage of NPs into highly regular and immunol. relevant conformations. The concn. of the ion Fe2+, salt, and fusion linker also contributed to the assembly in vitro, and the stability of the NPs. The kinetic "pace-keeping" role of chaperna in the super mol. assembly of antigen monomers holds promise for the development and delivery of NPs and virus-like particles as recombinant vaccines and for serol. detection of viral infections.
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132Carter, D. C.; Wright, B.; Jerome, W. G.; Rose, J. P.; Wilson, E. A Unique Protein Self-Assembling Nanoparticle with Significant Advantages in Vaccine Development and Production. J. Nanomater. 2020, 2020, 4297937, DOI: 10.1155/2020/4297937Google ScholarThere is no corresponding record for this reference.
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133Gelperina, S.; Kisich, K.; Iseman, M. D.; Heifets, L. The Potential Advantages of Nanoparticle Drug Delivery Systems in Chemotherapy of Tuberculosis. Am. J. Respir. Crit. Care Med. 2005, 172, 1487– 1490, DOI: 10.1164/rccm.200504-613PPGoogle Scholar133https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD2MnlsFeiuw%253D%253D&md5=3cd1441a228062dc8c82e3501b068e49The potential advantages of nanoparticle drug delivery systems in chemotherapy of tuberculosisGelperina Svetlana; Kisich Kevin; Iseman Michael D; Heifets LeonidAmerican journal of respiratory and critical care medicine (2005), 172 (12), 1487-90 ISSN:1073-449X.Nanoparticle-based drug delivery systems have considerable potential for treatment of tuberculosis (TB). The important technological advantages of nanoparticles used as drug carriers are high stability, high carrier capacity, feasibility of incorporation of both hydrophilic and hydrophobic substances, and feasibility of variable routes of administration, including oral application and inhalation. Nanoparticles can also be designed to allow controlled (sustained) drug release from the matrix. These properties of nanoparticles enable improvement of drug bioavailability and reduction of the dosing frequency, and may resolve the problem of nonadherence to prescribed therapy, which is one of the major obstacles in the control of TB epidemics. This article highlights some of the issues of nanotechnology relevant to the anti-TB drugs.
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134Singh, R.; Lillard, J. W. Nanoparticle-Based Targeted Drug Delivery. Exp. Mol. Pathol. 2009, 86, 215– 223, DOI: 10.1016/j.yexmp.2008.12.004Google Scholar134https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXlslWhtrs%253D&md5=51bbe150de7e5f9db5c27a9717198dffNanoparticle-based targeted drug deliverySingh, Rajesh; Lillard, James W.Experimental and Molecular Pathology (2009), 86 (3), 215-223CODEN: EXMPA6; ISSN:0014-4800. (Elsevier B.V.)A review. Nanotechnol. could be defined as the technol. that has allowed for the control, manipulation, study, and manuf. of structures and devices in the "nanometer" size range. These nano-sized objects, e.g., "nanoparticles", take on novel properties and functions that differ markedly from those seen from items made of identical materials. The small size, customized surface, improved soly., and multi-functionality of nanoparticles will continue to open many doors and create new biomedical applications. Indeed, the novel properties of nanoparticles offer the ability to interact with complex cellular functions in new ways. This rapidly growing field requires cross-disciplinary research and provides opportunities to design and develop multifunctional devices that can target, diagnose, and treat devastating diseases such as cancer. This article presents an overview of nanotechnol. for the biologist and discusses the attributes of the authors' novel XPclad nanoparticle formulation that has shown efficacy in treating solid tumors, single dose vaccination, and oral delivery of therapeutic proteins.
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135Sung, J. C.; Pulliam, B. L.; Edwards, D. A. Nanoparticles for Drug Delivery to the Lungs. Trends Biotechnol. 2007, 25, 563– 570, DOI: 10.1016/j.tibtech.2007.09.005Google Scholar135https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhtlCru7nK&md5=9a83415324703aa9cf44720616b4fff4Nanoparticles for drug delivery to the lungsSung, Jean C.; Pulliam, Brian L.; Edwards, David A.Trends in Biotechnology (2007), 25 (12), 563-570CODEN: TRBIDM; ISSN:0167-7799. (Elsevier B.V.)A review. The lungs are an attractive route for non-invasive drug delivery with advantages for both systemic and local applications. Incorporating therapeutics with polymeric nanoparticles offers addnl. degrees of manipulation for delivery systems, providing sustained release and the ability to target specific cells and organs. However, nanoparticle delivery to the lungs has many challenges including formulation instability due to particle-particle interactions and poor delivery efficiency due to exhalation of low-inertia nanoparticles. Thus, novel methods formulating nanoparticles into the form of micron-scale dry powders were developed. These carrier particles exhibit improved handling and delivery, while releasing nanoparticles upon deposition in the lungs. This review covers the development of nanoparticle formulations for pulmonary delivery as both individual nanoparticles and encapsulated within carrier particles.
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136Arruebo, M.; Fernández-Pacheco, R.; Ibarra, M. R.; Santamaría, J. Magnetic Nanoparticles for Drug Delivery. Nano Today 2007, 2, 22– 32, DOI: 10.1016/S1748-0132(07)70084-1Google ScholarThere is no corresponding record for this reference.
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137Bryan, W. W.; Medhi, R.; Marquez, M. D.; Rittikulsittichai, S.; Tran, M.; Lee, T. R. Porous Silver-Coated pNIPAM-Co-AAc Hydrogel Nanocapsules. Beilstein J. Nanotechnol. 2019, 10, 1973– 1982, DOI: 10.3762/bjnano.10.194Google Scholar137https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXitlShsb3K&md5=dcfc82e7827e3ec8238b2cc979f958e9Porous silver-coated pNIPAM-co-AAc hydrogel nanocapsulesBryan, William W.; Medhi, Riddhiman; Marquez, Maria D.; Rittikulsittichai, Supparesk; Tran, Michael; Lee, T. RandallBeilstein Journal of Nanotechnology (2019), 10 (), 1973-1982CODEN: BJNEAH; ISSN:2190-4286. (Beilstein-Institut zur Foerderung der Chemischen Wissenschaften)This paper describes the prepn. and characterization of a new type of core-shell nanoparticle in which the structure consists of a hydrogel core encapsulated within a porous silver shell. The thermo-responsive hydrogel cores were prepd. by surfactant-free emulsion polymn. of a selected mixt. of N-isopropylacrylamide (NIPAM) and acrylic acid (AAc). The hydrogel cores were then encased within either a porous or complete silver shell for which the localized surface plasmon resonance (LSPR) extends from visible to near-IR (NIR) wavelengths (i.e., max varies from 550 to 1050 nm, depending on the porosity), allowing for reversible contraction and swelling of the hydrogel via photothermal heating of the surrounding silver shell. Given that NIR light can pass through tissue, and the silver shell is porous, this system can serve as a platform for the smart delivery of payloads stored within the hydrogel core. The morphol. and compn. of the composite nanoparticles were characterized by SEM, TEM, and FTIR, resp. UV-vis spectroscopy was used to characterize the optical properties.
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138Tacken, P. J.; de Vries, I. J. M.; Torensma, R.; Figdor, C. G. Dendritic-Cell Immunotherapy: From Ex Vivo Loading to In Vivo Targeting. Nat. Rev. Immunol. 2007, 7, 790– 802, DOI: 10.1038/nri2173Google Scholar138https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhtVOrtbjL&md5=b462fa900c109e377467d4a2f37a20e4Dendritic-cell immunotherapy: from ex vivo loading to in vivo targetingTacken, Paul J.; de Vries, I. Jolanda M.; Torensma, Ruurd; Figdor, Carl G.Nature Reviews Immunology (2007), 7 (10), 790-802CODEN: NRIABX; ISSN:1474-1733. (Nature Publishing Group)A review. The realization that dendritic cells (DCs) orchestrate innate and adaptive immune responses has stimulated research on harnessing DCs to create more effective vaccines. Early clin. trials exploring autologous DCs that were loaded with antigens ex vivo to induce T-cell responses have provided proof of principle. Here, the authors discuss how direct targeting of antigens to DC surface receptors in vivo might replace laborious and expensive ex vivo culturing, and facilitate large-scale application of DC-based vaccination therapies.
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139Ciejka, J.; Wolski, K.; Nowakowska, M.; Pyrc, K.; Szczubiałka, K. Biopolymeric Nano/Microspheres for Selective and Reversible Adsorption of Coronaviruses. Mater. Sci. Eng., C 2017, 76, 735– 742, DOI: 10.1016/j.msec.2017.03.047Google Scholar139https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXltVWhtbs%253D&md5=fb115099d070e189ed074f796dbfd742Biopolymeric nano/microspheres for selective and reversible adsorption of coronavirusesCiejka, Justyna; Wolski, Karol; Nowakowska, Maria; Pyrc, Krzysztof; Szczubialka, KrzysztofMaterials Science & Engineering, C: Materials for Biological Applications (2017), 76 (), 735-742CODEN: MSCEEE; ISSN:0928-4931. (Elsevier B.V.)A novel biopolymeric material in the form of nano/microspheres was developed which was capable of adsorbing coronaviruses. The biopolymer was obtained by crosslinking of chitosan (CHIT) with genipin, a nontoxic compd. of plant origin, in inverted emulsion and reacting the chitosan nano/microspheres obtained (CHIT-NS/MS) with glycidyltrimethyl-ammonium chloride (GTMAC). As a result the nano/microspheres of N-(2-hydroxypropyl)-3-trimethyl chitosan (HTCC-NS/MS) were obtained. HTCC-NS/MS were studied as the adsorbents of human coronavirus NL63 (HCoV-NL63), mouse hepatitis virus (MHV), and human coronavirus HCoV-OC43 particles in aq. virus suspensions. By studying cytopathic effect (CPE) caused by these viruses and performing PCR analyses it was found HTCC-NS/MS strongly adsorb the particles of HCoV-NL63 virus, moderately adsorb mouse hepatitis virus (MHV) particles, but do not adsorb HCoV-OC43 coronavirus. The adsorption capacity of HTCC-NS/MS well correlated with the antiviral activity of sol. HTCC against a given virus. Importantly, it was shown that HCoV-NL63 particles could be desorbed from the HTCC-NS/MS surface with a salt soln. of high ionic strength with retention of virus virulence. The obtained material may be applied for the removal of coronaviruses, purifn. and concn. of virus samples obtained from biol. matrixes and for purifn. of water from pathogenic coronaviruses.
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140Xu, Y.; Yuen, P.-W.; Lam, J. K. -W. Intranasal DNA Vaccine for Protection against Respiratory Infectious Diseases: The Delivery Perspectives. Pharmaceutics 2014, 6, 378– 415, DOI: 10.3390/pharmaceutics6030378Google Scholar140https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhs12qtL%252FJ&md5=d92affc86a4dfd5239fa92b4124ccb8eIntranasal DNA vaccine for protection against respiratory infectious diseases: the delivery perspectivesXu, Yingying; Yuen, Pak-Wai; Lam, Jenny Ka-WingPharmaceutics (2014), 6 (3), 378-415CODEN: PHARK5; ISSN:1999-4923. (MDPI AG)A review. Intranasal delivery of DNA vaccines has become a popular research area recently. It offers some distinguished advantages over parenteral and other routes of vaccine administration. Nasal mucosa as site of vaccine administration can stimulate respiratory mucosal immunity by interacting with the nasopharyngeal-assocd. lymphoid tissues (NALT). Different kinds of DNA vaccines are investigated to provide protection against respiratory infectious diseases including tuberculosis, coronavirus, influenza and respiratory syncytial virus (RSV) etc. DNA vaccines have several attractive development potential, such as producing cross-protection towards different virus subtypes, enabling the possibility of mass manuf. in a relatively short time and a better safety profile. The biggest obstacle to DNA vaccines is low immunogenicity. One of the approaches to enhance the efficacy of DNA vaccine is to improve DNA delivery efficiency. This review provides insight on the development of intranasal DNA vaccine for respiratory infections, with special attention paid to the strategies to improve the delivery of DNA vaccines using non-viral delivery agents.
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141Tse, G. M. -K.; To, K.-F.; Chan, P. K.-S.; Lo, A. W. I.; Ng, K.-C.; Wu, A.; Lee, N.; Wong, H.-C.; Mak, S.-M.; Chan, K.-F.; Hui, D. S. C.; Sung, J. J. -Y.; Ng, H.-K. Pulmonary Pathological Features in Coronavirus Associated Severe Acute Respiratory Syndrome (SARS). J. Clin. Pathol. 2004, 57, 260– 265, DOI: 10.1136/jcp.2003.013276Google Scholar141https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD2c7jsVGltw%253D%253D&md5=6c43791207beb06113fe50b0e43f93edPulmonary pathological features in coronavirus associated severe acute respiratory syndrome (SARS)Tse G M-K; To K-F; Chan P K-S; Lo A W I; Ng K-C; Wu A; Lee N; Wong H-C; Mak S-M; Chan K-F; Hui D S C; Sung J J-Y; Ng H-KJournal of clinical pathology (2004), 57 (3), 260-5 ISSN:0021-9746.BACKGROUND: Severe acute respiratory syndrome (SARS) became a worldwide outbreak with a mortality of 9.2%. This new human emergent infectious disease is dominated by severe lower respiratory illness and is aetiologically linked to a new coronavirus (SARS-CoV). METHODS: Pulmonary pathology and clinical correlates were investigated in seven patients who died of SARS in whom there was a strong epidemiological link. Investigations include a review of clinical features, morphological assessment, histochemical and immunohistochemical stainings, ultrastructural study, and virological investigations in postmortem tissue. RESULTS: Positive viral culture for coronavirus was detected in most premortem nasopharyngeal aspirate specimens (five of six) and postmortem lung tissues (two of seven). Viral particles, consistent with coronavirus, could be detected in lung pneumocytes in most of the patients. These features suggested that pneumocytes are probably the primary target of infection. The pathological features were dominated by diffuse alveolar damage, with the presence of multinucleated pneumocytes. Fibrogranulation tissue proliferation in small airways and airspaces (bronchiolitis obliterans organising pneumonia-like lesions) in subpleural locations was also seen in some patients. CONCLUSIONS: Viable SARS-CoV could be isolated from postmortem tissues. Postmortem examination allows tissue to be sampled for virological investigations and ultrastructural examination, and when coupled with the appropriate lung morphological changes, is valuable to confirm the diagnosis of SARS-CoV, particularly in clinically unapparent or suspicious but unconfirmed cases.
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142Gu, J.; Korteweg, C. Pathology and Pathogenesis of Severe Acute Respiratory Syndrome. Am. J. Pathol. 2007, 170, 1136– 1147, DOI: 10.2353/ajpath.2007.061088Google Scholar142https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXkvFymsLw%253D&md5=9762a0dc94960ea810377891759f07bbPathology and pathogenesis of severe acute respiratory syndromeGu, Jiang; Korteweg, ChristineAmerican Journal of Pathology (2007), 170 (4), 1136-1147CODEN: AJPAA4; ISSN:0002-9440. (American Society for Investigative Pathology)A review. Severe acute respiratory syndrome (SARS) is an emerging infectious viral disease characterized by severe clin. manifestations of the lower respiratory tract. The pathogenesis of SARS is highly complex, with multiple factors leading to severe injury in the lungs and dissemination of the virus to several other organs. The SARS coronavirus targets the epithelial cells of the respiratory tract, resulting in diffuse alveolar damage. Several organs/cell types may be infected in the course of the illness, including mucosal cells of the intestines, tubular epithelial cells of the kidneys, neurons of the brain, and several types of immune cells, and certain organs may suffer from indirect injury. Extensive studies have provided a basic understanding of the pathogenesis of this disease. In this review we describe the most significant pathol. features of SARS, explore the etiol. factors causing these pathol. changes, and discuss the major pathogenetic mechanisms. The latter include dysregulation of cytokines/chemokines, deficiencies in the innate immune response, direct infection of immune cells, direct viral cytopathic effects, down-regulation of lung protective angiotensin converting enzyme 2, autoimmunity, and genetic factors. It seems that both abnormal immune responses and injury to immune cells may be key factors in the pathogenesis of this new disease.
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143Nascimento, T. L.; Hillaireau, H.; Fattal, E. Nanoscale Particles for Lung Delivery of siRNA. J. Drug Delivery Sci. Technol. 2012, 22, 99– 108, DOI: 10.1016/S1773-2247(12)50010-9Google Scholar143https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XkvFyisbs%253D&md5=cc42c312220019972db3ff63d5d588f4Nanoscale particles for lung delivery of siRNANascimento, T. L.; Hillaireau, H.; Fattal, E.Journal of Drug Delivery Science and Technology (2012), 22 (1), 99-108CODEN: JDDSAL; ISSN:1773-2247. (Editions de Sante)A review. Small interfering RNAs (siRNAs) are potent mols. capable of blocking gene expression after entering cell cytoplasm. Despite their strong efficacy, they need to be carried by nanoscale delivery systems that can protect them against degrdn. in biol. fluids, increase their cellular uptake and favor their subcellular distribution. Several studies have highlighted the potential of local pulmonary delivery of siRNAs for the treatment of lung diseases. For this purpose, nanoscale delivery systems were addressed to target passively or actively the target cell. This review discusses the possibilities of approaching lung delivery of nanoscale particles carrying siRNAs.
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144Wang, F.; Kream, R. M.; Stefano, G. B. An Evidence Based Perspective on mRNA-SARS-CoV-2 Vaccine Development. Med. Sci. Monit. 2020, 26, 924700, DOI: 10.12659/MSM.924700Google ScholarThere is no corresponding record for this reference.
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145Liu, C.; Zhou, Q.; Li, Y.; Garner, L. V.; Watkins, S. P.; Carter, L. J.; Smoot, J.; Gregg, A. C.; Daniels, A. D.; Jervey, S.; Albaiu, D. Research and Development on Therapeutic Agents and Vaccines for Covid-19 and Related Human Coronavirus Diseases. ACS Cent. Sci. 2020, 6, 315– 331, DOI: 10.1021/acscentsci.0c00272Google Scholar145https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXkslWrsbo%253D&md5=fa29fb4cc3353a140e3a6a74059a99b1Research and Development on Therapeutic Agents and Vaccines for COVID-19 and Related Human Coronavirus DiseasesLiu, Cynthia; Zhou, Qiongqiong; Li, Yingzhu; Garner, Linda V.; Watkins, Steve P.; Carter, Linda J.; Smoot, Jeffrey; Gregg, Anne C.; Daniels, Angela D.; Jervey, Susan; Albaiu, DanaACS Central Science (2020), 6 (3), 315-331CODEN: ACSCII; ISSN:2374-7951. (American Chemical Society)A review. Since the outbreak of the novel coronavirus disease COVID-19, caused by the SARS-CoV-2 virus, this disease has spread rapidly around the globe. Considering the potential threat of a pandemic, scientists and physicians have been racing to understand this new virus and the pathophysiol. of this disease to uncover possible treatment regimens and discover effective therapeutic agents and vaccines. To support the current research and development, CAS has produced a special report to provide an overview of published scientific information with an emphasis on patents in the CAS content collection. It highlights antiviral strategies involving small mols. and biologics targeting complex mol. interactions involved in coronavirus infection and replication. The drug-repurposing effort documented herein focuses primarily on agents known to be effective against other RNA viruses including SARS-CoV and MERS-CoV. The patent anal. of coronavirus-related biologics includes therapeutic antibodies, cytokines, and nucleic acid-based therapies targeting virus gene expression as well as various types of vaccines. More than 500 patents disclose methodologies of these four biologics with the potential for treating and preventing coronavirus infections, which may be applicable to COVID-19. The information included in this report provides a strong intellectual groundwork for the ongoing development of therapeutic agents and vaccines.
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146Frede, A.; Neuhaus, B.; Knuschke, T.; Wadwa, M.; Kollenda, S.; Klopfleisch, R.; Hansen, W.; Buer, J.; Bruder, D.; Epple, M.; Westendorf, A. M. Local Delivery of siRNA-Loaded Calcium Phosphate Nanoparticles Abates Pulmonary Inflammation. Nanomedicine 2017, 13, 2395– 2403, DOI: 10.1016/j.nano.2017.08.001Google Scholar146https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtlegsb3K&md5=59331b85b1b1fc6333750c5c68de0941Local delivery of siRNA-loaded calcium phosphate nanoparticles abates pulmonary inflammationFrede, Annika; Neuhaus, Bernhard; Knuschke, Torben; Wadwa, Munisch; Kollenda, Sebastian; Klopfleisch, Robert; Hansen, Wiebke; Buer, Jan; Bruder, Dunja; Epple, Matthias; Westendorf, Astrid M.Nanomedicine (New York, NY, United States) (2017), 13 (8), 2395-2403CODEN: NANOBF; ISSN:1549-9634. (Elsevier)The local interference of cytokine signaling mediated by siRNA-loaded nanoparticles might be a promising new therapeutic approach to dampen inflammation during pulmonary diseases. For the local therapeutic treatment of pulmonary inflammation, we produced multi-shell nanoparticles consisting of a calcium phosphate core, coated with siRNAs directed against pro-inflammatory mediators, encapsulated into poly(lactic-co-glycolic acid), and coated with a final outer layer of polyethylenimine. Nasal instillation of nanoparticles loaded with a mixt. of siRNAs directed against different cytokines to mice suffering from TH1 cell-mediated lung inflammation, or of siRNA directed against NS-1 in an influenza infection model led to a significant redn. of target gene expression which was accompanied by distinct amelioration of lung inflammation in both models. Thus, this study provides strong evidence that the specific and local modulation of the inflammatory response by CaP/PLGA nanoparticle-mediated siRNA delivery could be a promising approach for the treatment of inflammatory disorders of the lung.
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147Dykman, L. A.; Khlebtsov, N. G. Immunological Properties of Gold Nanoparticles. Chem. Sci. 2017, 8, 1719– 1735, DOI: 10.1039/C6SC03631GGoogle Scholar147https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhvVKgtLfE&md5=03448b78fd528a6017504d1dde11a349Immunological properties of gold nanoparticlesDykman, Lev A.; Khlebtsov, Nikolai G.Chemical Science (2017), 8 (3), 1719-1735CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)In the past decade, gold nanoparticles have attracted strong interest from the nanobiotechnol. community owing to the significant progress made in robust and easy-to-make synthesis technologies, in surface functionalization, and in promising biomedical applications. These include bioimaging, gene diagnostics, anal. sensing, photothermal treatment of tumors, and targeted delivery of various biomol. and chem. cargos. For the last-named application, gold nanoparticles should be properly fabricated to deliver the cargo into the targeted cells through effective endocytosis. In this review, we discuss recent progress in understanding the selective penetration of gold nanoparticles into immune cells. The interaction of gold nanoparticles with immune cell receptors is discussed. As distinct from other published reviews, we present a summary of the immunol. properties of gold nanoparticles. This review also summarizes what is known about the application of gold nanoparticles as an antigen carrier and adjuvant in immunization for the prepn. of antibodies in vivo. For each of the above topics, the basic principles, recent advances, and current challenges are discussed. Thus, this review presents a detailed anal. of data on interaction of gold nanoparticles with immune cells. Emphasis is placed on the systematization of data over prodn. of antibodies by using gold nanoparticles and adjuvant properties of gold nanoparticles. Specifically, we start our discussion with current data on interaction of various gold nanoparticles with immune cells. The next section describes existing technologies to improve prodn. of antibodies in vivo by using gold nanoparticles conjugated with specific ligands. Finally, we describe what is known about adjuvant properties of bare gold or functionalized nanoparticles. In the Conclusion section, we present a short summary of reported data and some challenges and perspectives.
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148Comber, J. D.; Bamezai, A. Gold Nanoparticles (AuNPs): A New Frontier in Vaccine Delivery. J. Nanomed. Biother. Discovery 2015, 5, e139, DOI: 10.4172/2155-983X.1000e139Google Scholar148https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXmtVGku7Y%253D&md5=a7c20256e9843780d398e1c2f540adbaGold nanoparticles (AuNPs): a new frontier in vaccine deliveryComber, Joseph D.; Bamezai, AnilJournal of Nanomedicine & Biotherapeutic Discovery (2015), 5 (4), 139/1-139/4CODEN: JNBDB3; ISSN:2155-983X. (OMICS International)There is no expanded citation for this reference.
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149Niikura, K.; Matsunaga, T.; Suzuki, T.; Kobayashi, S.; Yamaguchi, H.; Orba, Y.; Kawaguchi, A.; Hasegawa, H.; Kajino, K.; Ninomiya, T.; Ijiro, K.; Sawa, H. Gold Nanoparticles as a Vaccine Platform: Influence of Size and Shape on Immunological Responses In Vitro and In Vivo. ACS Nano 2013, 7, 3926– 3938, DOI: 10.1021/nn3057005Google Scholar149https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXmvVylsrw%253D&md5=7b184b14dba10fafe46b9f63850b2e7cGold Nanoparticles as a Vaccine Platform: Influence of Size and Shape on Immunological Responses in Vitro and in VivoNiikura, Kenichi; Matsunaga, Tatsuya; Suzuki, Tadaki; Kobayashi, Shintaro; Yamaguchi, Hiroki; Orba, Yasuko; Kawaguchi, Akira; Hasegawa, Hideki; Kajino, Kiichi; Ninomiya, Takafumi; Ijiro, Kuniharu; Sawa, HirofumiACS Nano (2013), 7 (5), 3926-3938CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)This paper demonstrates how the shape and size of gold nanoparticles (AuNPs) affect immunol. responses in vivo and in vitro for the prodn. of antibodies for West Nile virus (WNV). The authors prepd. spherical (20 and 40 nm in diam.), rod (40×10 nm), and cubic (40×40×40 nm) AuNPs as adjuvants and coated them with WNV envelope (E) protein. The authors measured anti-WNVE antibodies after inoculation of these WNVE-coated AuNPs (AuNP-Es) into mice. The 40 nm spherical AuNP-Es (Sphere40-Es) induced the highest level of WNVE-specific antibodies, while rod AuNP-Es (Rod-Es) induced only 50% of that of Sphere40-E. To examine the mechanisms of the shape-dependent WNVE antibody prodn., the authors next measured the efficiency of cellular uptake of AuNP-Es into RAW264.7 macrophage cells and bone-marrow-derived dendritic cells (BMDCs) and the subsequent cytokine secretion from BMDCs. The uptake of Rod-Es into the cells proceeded more efficiently than those of Sphere-Es or cubic WNVE-coated AuNPs (Cube-Es), suggesting that antibody prodn. was not dependent on the uptake efficiency of the different AuNP-Es. Cytokine prodn. from BMDCs treated with the AuNP-Es revealed that only Rod-E-treated cells produced significant levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18), indicating that Rod-Es activated inflammasome-dependent cytokine secretion. Meanwhile, Sphere40-Es and Cube-Es both significantly induced inflammatory cytokine prodn., including tumor necrosis factor-α (TNF-α), IL-6, IL-12, and granulocyte macrophage colony-stimulating factor (GM-CSF). These results suggested that AuNPs are effective vaccine adjuvants and enhance the immune response via different cytokine pathways depending on their sizes and shapes.
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Abstract
Figure 1
Figure 1. (a) The SARS-CoV-2 structure is illustrated, with its structural viral proteins indicated. Reproduced with permission from ref (12). Copyright 2020 American Chemical Society. (b) Scanning electron microscopy (SEM) image showing the particulate nature of SARS-CoV-2 (yellow) isolated from a patient in the U.S., emerging from the surface of cells (pink) cultured in the laboratory. Image captured and colorized at NIAID’s Rocky Mountain Laboratories (RML) in Hamilton, Montana. Credit: NIAID-RML. (c–e) Transmission electron microscopy (TEM) images show SARS-CoV-2 isolated from a patient in the U.S. Virus particles are shown emerging from the surface of cells cultured in the laboratory. The crown-like spikes on the outer edge of the virus particles give coronaviruses their name. Image captured and colorized at NIAID’s RML in Hamilton, Montana. Credit: NIAID-RML.
Figure 2
Figure 2. Colorimetric detection of RNAs based on a disulfide-induced self-assembly process. (a) Procedures for preventing salt-induced aggregation of AuNPs by disulfide-induced self-assembly of long thiol-modified dsDNAs in the presence of targets. (b) Salt-induced aggregation of AuNPs in the absence of targets. Adapted with permission from reference (28). Copyright 2019 American Chemical Society.
Figure 3
Figure 3. Schematic illustrations of (a) cDNA-receptor-functionalized AuNI based on the reaction with thiol–cDNA ligands, (b) the hybridization of two complementary strands, and (c) the hybridization of two partially matched sequences. Adapted with permission from reference (46). Copyright 2020 American Chemical Society.
Figure 4
Figure 4. Schematic illustration of the formation of ZrQDs and Fe3O4@Au MPNP nanohybrid structures for magnetoplasmonic–fluorescent virus detection. Adapted with permission from reference (38). Copyright 2018 Elsevier.
Figure 5
Figure 5. (a) Diagram of full-length SARS-CoV-2 S protein with a 3xFLAG tag. S1: receptor-binding subunit; S2: membrane fusion subunit; TM: transmembrane domain; NTD: N-terminal domain; pFP: potential fusion peptide; HR-N: heptad repeat-N; HR-C: heptad repeat-C. Reproduced with permission from ref (83). Copyright 2020 Springer Nature. (b) Potential mechanism by which chloroquine exerts therapeutic effects against COVID-19. The proposed mechanism involves chloroquine-induced suppression of PICALM, which prevents endocytosis-mediated uptake of nanoparticles, including SARS-CoV-2. Adapted with permission from ref (85). Copyright 2020 Springer Nature.
Figure 6
Figure 6. (a) Dose relationship between the viral entry inhibitory efficiency and amount of added CCM-CDs. (b) Zeta potentials of CCM-CDs, PEDV, and CCM-CDs pretreated with PEDV, indicating aggregation of PEDV upon treatment with CDs. Reproduced with permission from ref (76). Copyright 2018 American Chemical Society.
Figure 7
Figure 7. (a) Schematic diagram of the inhibition of MERS-CoV S2-subunit-mediated membrane fusion with an HR1 inhibitor (left); the HR1 inhibitor can inhibit HR1/HR2 complex (6-HB)-mediated membrane fusion and prevent MERS-CoV infection (right). (b) Body weights of mice in both the PIH–AuNR group and control group steadily increased, demonstrating excellent biosafety of PIH–AuNRs. (c) Quantification of cell fusion in the presence of PIH, AuNRs, and PIH–AuNRs. (d) Inhibitory effect of PIH–AuNRs on MERS-CoV S2-subunit-mediated cell fusion, indicating that PIH–AuNRs are more potent anti-MERS agents than the peptide PIH. Reproduced with permission from ref (59). Copyright 2019 American Chemical Society.
Figure 8
Figure 8. Possible mechanisms of the antiviral activity of Ag2S NCs via inhibition of the synthesis of viral RNA and viral budding due to the production of ISGs and upregulation of proinflammatory cytokines. Reproduced with permission from ref (74). Copyright 2018 American Chemical Society.
Figure 9
Figure 9. (a) Viricidal activity of AuNPs coated with MES or MUS. (b) Heparin, MES-coated AuNP, and MUS:OT-coated AuNP viral infectivity curves (blue) and viricidal assays at concentrations corresponding to the EC90 (black) and after dilution (red). (c) Viricidal activity of MUS:OT-coated AuNPs against HPV, RSV, VSV (indicated as LV), and dengue virus (DENV-2). (d) MUS:OT-coated AuNP-mediated inhibition of viral infectivity against HSV-2 versus time (min). Reproduced and adapted with permission from ref (57). Copyright 2017 Springer Nature.
Figure 10
Figure 10. (a) Effect of CQD on HCoV by inhibition of S protein–receptor interaction (top) and viral RNA genome replication (bottom). (b) Viral inhibition using CQDs-3, CQDs-5, and CQDs-6. Reproduced and adapted with permission from ref (75). Copyright 2019 American Chemical Society.
Figure 11
Figure 11. (a) Neutralization titers of coronavirus-spike-vaccinated mice. Serum from mice vaccinated with the indicated mix of spike protein and adjuvant was analyzed for neutralization capability and geometric mean titer (GMT), as graphed for all groups (10 mice per group). Stars denote statistically significant differences (p < 0.05). Reproduced with permission from ref (9). Copyright 2014 Elsevier. (b) Titers of neutralizing serum antibody against MERS-CoV in immunized mice. The rate of virus reduction for each group was calculated by comparison with the number of plaques in the control group (with PBS). The red dotted line indicates a 50% reduction in the virus. The mean reduction ± standard deviation values are shown. Reproduced with permission from ref (11). Copyright 2018 Elsevier. (c) Synthetic scheme and computer models for the formation of coiled-coil template-based complete peptide nanoparticles using the HRC region of the S epitope. The inset shows the various segments of the SARS-CoV S protein. Reproduced with permission from ref (124). Copyright 2009 Wiley.
Figure 12
Figure 12. (a) Schematic illustration of dendritic cells targeting chitosan nanoparticles loaded with N proteins. Reproduced with permission from ref (93). Copyright 2012 American Chemical Society. (b) Survival of iBALT-induced PCN- and PBS-treated mice following challenge with SARS-coronavirus. All PCN-treated mice (■) survived infection with SARS-CoV, whereas all of the PBS-treated control mice (Δ) were dead by day 4 postinfection. (c) PCN-treated mice (■) maintained their bodyweight following SARS-CoV infection, whereas PBS-treated control mice (Δ) lost significant amounts of body weight shortly after infection. Reproduced with permission from ref (126). Copyright 2009 Wiley et al.
Figure 13
Figure 13. Characterization of adjuvant-loaded viromimetic nanoparticles. (a) Schematic showing the preparation of the viromimetic nanoparticle vaccine. Hollow PLGA nanoparticles with encapsulated adjuvant and surface maleimide linkers were prepared using a double-emulsion technique. Recombinant viral antigens were then conjugated to the surface of nanoparticles via a thiol–maleimide linkage. (b) Cryo-electron microscopy of cdGMP-loaded hollow nanoparticles. (c) Size distribution of nanoparticles determined by dynamic light scattering (DLS). (d) In vitro release profiles of cdGMP from PLGA hollow nanoparticles at pH 5 and 7. Reproduced with permission from ref (127). Copyright 2019 WILEY-VCH Verlag GmbH & Co., KGaA, Weinheim.
Figure 14
Figure 14. (a) Schematic depiction of the preparation of avian coronavirus sVLPs. sVLPs are prepared in optimized mixtures containing viral proteins and 100 nm gold nanoparticles via spontaneous protein corona formation. (b) Transmission electron microscopy of sVLPs (left) and native IBV virions (right) following immunogold staining against IBV spike proteins. Scale bars = 50 nm. (c) Size and zeta potential of AuNPs, sVLPs, and native IBV virions as analyzed by nanoparticle tracking analysis. Bars represent the mean ± s.d. (n = 3). (d) Vaccination, tissue sample collection, and virus challenge schedule in an avian model of coronavirus infection. (e) Virus-specific serum IgG titers observed in animals vaccinated with free proteins, a commercial whole inactivated virus (WIV) vaccine, and sVLPs. Lines and boxes represent the upper extreme; 25th, 50th, and 75th percentiles; and lower extreme (n = 6). (f) Virus-specific serum IgA titers in animals vaccinated with the different formulations. Lines and boxes represent the upper extreme; 25th, 50th, and 75th percentiles; and lower extreme (n = 6). Reproduced with permission from ref (122). Copyright 2016 Elsevier.
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References
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This article references 149 other publications.
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1Chan, J. F. -W.; Yuan, S.; Kok, K.-H.; To, K. K. -W.; Chu, H.; Yang, J.; Xing, F.; Liu, J.; Yip, C. C. -Y.; Poon, R. W. -S.; Tsoi, H.-W.; Lo, S. K. -F.; Chan, K.-H.; Poon, V. K. -M.; Chan, W.-M.; Ip, J. D.; Cai, J.-P.; Cheng, V. C. -C.; Chen, H.; Hui, C. K. -M.; Yuen, K.-Y. A Familial Cluster of Pneumonia Associated with the 2019 Novel Coronavirus Indicating Person-to-Person Transmission: A Study of a Family Cluster. Lancet 2020, 395, 514– 523, DOI: 10.1016/S0140-6736(20)30154-91https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhs1Ojsro%253D&md5=a00abba6fd95be357f1b4a0152da93c0A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family clusterChan, Jasper Fuk-Woo; Yuan, Shuofeng; Kok, Kin-Hang; To, Kelvin Kai-Wang; Chu, Hin; Yang, Jin; Xing, Fanfan; Liu, Jieling; Yip, Cyril Chik-Yan; Poon, Rosana Wing-Shan; Tsoi, Hoi-Wah; Lo, Simon Kam-Fai; Chan, Kwok-Hung; Poon, Vincent Kwok-Man; Chan, Wan-Mui; Ip, Jonathan Daniel; Cai, Jian-Piao; Cheng, Vincent Chi-Chung; Chen, Honglin; Hui, Christopher Kim-Ming; Yuen, Kwok-YungLancet (2020), 395 (10223), 514-523CODEN: LANCAO; ISSN:0140-6736. (Elsevier Ltd.)An ongoing outbreak of pneumonia assocd. with a novel coronavirus was reported in Wuhan city, Hubei province, China. Affected patients were geog. linked with a local wet market as a potential source. No data on person-to-person or nosocomial transmission have been published to date. In this study, we report the epidemiol., clin., lab., radiol., and microbiol. findings of five patients in a family cluster who presented with unexplained pneumonia after returning to Shenzhen, Guangdong province, China, after a visit to Wuhan, and an addnl. family member who did not travel to Wuhan. Phylogenetic anal. of genetic sequences from these patients were done. From Jan 10, 2020, we enrolled a family of six patients who travelled to Wuhan from Shenzhen between Dec 29, 2019 and Jan 4, 2020. Of six family members who travelled to Wuhan, five were identified as infected with the novel coronavirus. Addnl., one family member, who did not travel to Wuhan, became infected with the virus after several days of contact with four of the family members. None of the family members had contacts with Wuhan markets or animals, although two had visited a Wuhan hospital. Five family members (aged 36-66 years) presented with fever, upper or lower respiratory tract symptoms, or diarrhea, or a combination of these 3-6 days after exposure. They presented to our hospital (The University of Hong Kong-Shenzhen Hospital, Shenzhen) 6-10 days after symptom onset. They and one asymptomatic child (aged 10 years) had radiol. ground-glass lung opacities. Older patients (aged >60 years) had more systemic symptoms, extensive radiol. ground-glass lung changes, lymphopenia, thrombocytopenia, and increased C-reactive protein and lactate dehydrogenase levels. The nasopharyngeal or throat swabs of these six patients were neg. for known respiratory microbes by point-of-care multiplex RT-PCR, but five patients (four adults and the child) were RT-PCR pos. for genes encoding the internal RNA-dependent RNA polymerase and surface Spike protein of this novel coronavirus, which were confirmed by Sanger sequencing. Phylogenetic anal. of these five patients' RT-PCR amplicons and two full genomes by next-generation sequencing showed that this is a novel coronavirus, which is closest to the bat severe acute respiratory syndrome (SARS)-related coronaviruses found in Chinese horseshoe bats. Our findings are consistent with person-to-person transmission of this novel coronavirus in hospital and family settings, and the reports of infected travelers in other geog. regions. The Shaw Foundation Hong Kong, Michael Seak-Kan Tong, Respiratory Viral Research Foundation Limited, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund Limited, Marina Man-Wai Lee, the Hong Kong Hainan Com. Assocn. South China Microbiol. Research Fund, Sanming Project of Medicine (Shenzhen), and High Level-Hospital Program (Guangdong Health Commission).
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2Huang, C.; Wang, Y.; Li, X.; Ren, L.; Zhao, J.; Hu, Y.; Zhang, L.; Fan, G.; Xu, J.; Gu, X.; Cheng, Z.; Yu, T.; Xia, J.; Wei, Y.; Wu, W.; Xie, X.; Yin, W.; Li, H.; Liu, M.; Xiao, Y.; Gao, H.; Guo, L.; Xie, J.; Wang, G.; Jiang, R.; Gao, Z.; Jin, Q.; Wang, J.; Cao, B. Clinical Features of Patients Infected with 2019 Novel Coronavirus in Wuhan, China. Lancet 2020, 395, 497– 506, DOI: 10.1016/S0140-6736(20)30183-52https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhs1Kqu7c%253D&md5=b279b965c1054d99e60f673859c03b49Clinical features of patients infected with 2019 novel coronavirus in Wuhan, ChinaHuang, Chaolin; Wang, Yeming; Li, Xingwang; Ren, Lili; Zhao, Jianping; Hu, Yi; Zhang, Li; Fan, Guohui; Xu, Jiuyang; Gu, Xiaoying; Cheng, Zhenshun; Yu, Ting; Xia, Jiaan; Wei, Yuan; Wu, Wenjuan; Xie, Xuelei; Yin, Wen; Li, Hui; Liu, Min; Xiao, Yan; Gao, Hong; Guo, Li; Xie, Jungang; Wang, Guangfa; Jiang, Rongmeng; Gao, Zhancheng; Jin, Qi; Wang, Jianwei; Cao, BinLancet (2020), 395 (10223), 497-506CODEN: LANCAO; ISSN:0140-6736. (Elsevier Ltd.)A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiol., clin., lab., and radiol. characteristics and treatment and clin. outcomes of these patients. All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analyzed data on patients with lab.-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiol. and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. By Jan 2, 2020, 41 admitted hospital patients had been identified as having lab.-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0-58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum prodn. (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0-13·0]). 26 (63%) Of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was assocd. with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiol., duration of human transmission, and clin. spectrum of disease need fulfilment by future studies. Ministry of Science and Technol., Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technol. Commission.
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3Wrapp, D.; Wang, N.; Corbett, K. S.; Goldsmith, J. A.; Hsieh, C.-L.; Abiona, O.; Graham, B. S.; McLellan, J. S. Cryo-EM Structure of the 2019-Ncov Spike in the Prefusion Conformation. Science 2020, 367, 1260– 1263, DOI: 10.1126/science.abb25073https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXkvFemt70%253D&md5=27d08cbb9a43d1da051a8a92a9f68aa5Cryo-EM structure of the 2019-nCoV spike in the prefusion conformationWrapp, Daniel; Wang, Nianshuang; Corbett, Kizzmekia S.; Goldsmith, Jory A.; Hsieh, Ching-Lin; Abiona, Olubukola; Graham, Barney S.; McLellan, Jason S.Science (Washington, DC, United States) (2020), 367 (6483), 1260-1263CODEN: SCIEAS; ISSN:1095-9203. (American Association for the Advancement of Science)The outbreak of a novel coronavirus (2019-nCoV) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure development, we detd. a 3.5-angstrom-resoln. cryo-electron microscopy structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also provide biophys. and structural evidence that the 2019-nCoV S protein binds angiotensin-converting enzyme 2 (ACE2) with higher affinity than does severe acute respiratory syndrome (SARS)-CoV S. Addnl., we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable the rapid development and evaluation of medical countermeasures to address the ongoing public health crisis.
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4Zhang, L.; Lin, D.; Sun, X.; Curth, U.; Drosten, C.; Sauerhering, L.; Becker, S.; Rox, K.; Hilgenfeld, R. Crystal Structure of SARS-CoV-2 Main Protease Provides a Basis for Design of Improved α-Ketoamide Inhibitors. Science 2020, 368, 409– 412, DOI: 10.1126/science.abb34054https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXnslKrtL8%253D&md5=9ac417c20f54c3327f9de9088b512d52Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitorsZhang, Linlin; Lin, Daizong; Sun, Xinyuanyuan; Curth, Ute; Drosten, Christian; Sauerhering, Lucie; Becker, Stephan; Rox, Katharina; Hilgenfeld, RolfScience (Washington, DC, United States) (2020), 368 (6489), 409-412CODEN: SCIEAS; ISSN:1095-9203. (American Association for the Advancement of Science)The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is a global health emergency. An attractive drug target among coronaviruses is the main protease (Mpro, also called 3CLpro) because of its essential role in processing the polyproteins that are translated from the viral RNA. We report the x-ray structures of the unliganded SARS-CoV-2 Mpro and its complex with an α-ketoamide inhibitor. This was derived from a previously designed inhibitor but with the P3-P2 amide bond incorporated into a pyridone ring to enhance the half-life of the compd. in plasma. On the basis of the unliganded structure, we developed the lead compd. into a potent inhibitor of the SARS-CoV-2 Mpro. The pharmacokinetic characterization of the optimized inhibitor reveals a pronounced lung tropism and suitability for administration by the inhalative route.
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5Gandhi, M.; Yokoe, D. S.; Havlir, D. V. Asymptomatic Transmission, the Achilles’ Heel of Current Strategies to Control Covid-19. N. Engl. J. Med. 2020, 382, 2158– 2160, DOI: 10.1056/NEJMe20097585https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtVGqsrfF&md5=9758bf5634365e6044e42b6c8b57b5b3Asymptomatic transmission, the Achilles' heel of current strategies to control Covid-19Gandhi, Monica; Yokoe, Deborah S.; Havlir, Diane V.New England Journal of Medicine (2020), 382 (22), 2158-2160CODEN: NEJMAG; ISSN:1533-4406. (Massachusetts Medical Society)A review. A brief editorial discussing the role of asymptomatic transmission in the spread and severity of the current SARS-CoV-2 pandemic. The authors contrast the differences between the current SARS-CoV-2 pandemic and the SARS-CoV-1 epidemic of 2003. High levels of SARS-CoV-2 virus are shed from the upper respiratory tract of patients, even before symptoms are obsd. In contrast, replication of SARS-CoV-1 occurs mainly in the lower respiratory tract, and viral shedding occurs later, when patients are symptomatic. Asymptomatic transmission of SARS-CoV-2 is the Achilles' heel of COVID-19 pandemic control through the public health strategies we have currently deployed. Because of this, testing of asymptomatic individuals, social distancing, and the general use of face masks in public spaces are the main tools to deal with this pandemic.
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6Rinaldi, A. Free, at Last! The Progress of New Disease Eradication Campaigns for Guinea Worm Disease and Polio, and the Prospect of Tackling Other Diseases. EMBO Rep. 2009, 10, 215– 221, DOI: 10.1038/embor.2009.196https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXisVOrt7s%253D&md5=c058c35bdc62879001a85d7bf9b3fc35Free, at last! The progress of new disease eradication campaigns for Guinea worm disease and polio, and the prospect of tackling other diseasesRinaldi, AndreaEMBO Reports (2009), 10 (3), 215-221CODEN: ERMEAX; ISSN:1469-221X. (Nature Publishing Group)There is no expanded citation for this reference.
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7Sued, O.; Figueroa, M. I.; Cahn, P. Clinical Challenges in HIV/AIDS: Hints for Advancing Prevention and Patient Management Strategies. Adv. Drug Delivery Rev. 2016, 103, 5– 19, DOI: 10.1016/j.addr.2016.04.0167https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XntVOmsL4%253D&md5=1adcabc206ee3f3a698a674fd470a78bClinical challenges in HIV/AIDS: Hints for advancing prevention and patient management strategiesSued, Omar; Figueroa, Maria Ines; Cahn, PedroAdvanced Drug Delivery Reviews (2016), 103 (), 5-19CODEN: ADDREP; ISSN:0169-409X. (Elsevier B.V.)Acquired immune deficiency syndrome has been one of the most devastating epidemics of the last century. The current est. for people living with the HIV is 36.9 million. Today, despite availability of potent and safe drugs for effective treatment, lifelong therapy is required for preventing HIV re-emergence from a pool of latently infected cells. However, recent evidence show the importance to expand HIV testing, to offer antiretroviral treatment to all infected individuals, and to ensure retention through all the cascade of care. In addn., circumcision, pre-exposure prophylaxis, and other biomedical tools are now available for included in a comprehensive preventive package. Use of all the available tools might allow cutting the HIV transmission in 2030. In this article, we review the status of the epidemic, the latest advances in prevention and treatment, the concept of treatment as prevention and the challenges and opportunities for the HIV cure agenda.
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8Sharma, J.; Shepardson, K.; Johns, L. L.; Wellham, J.; Avera, J.; Schwarz, B.; Rynda-Apple, A.; Douglas, T. A Self-Adjuvanted, Modular, Antigenic VLP for Rapid Response to Influenza Virus Variability. ACS Appl. Mater. Interfaces 2020, 12, 18211– 18224, DOI: 10.1021/acsami.9b217768https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXmt1erur8%253D&md5=1cc160e97a978a8dce1842636bc8ea17A Self-Adjuvanted, Modular, Antigenic VLP for Rapid Response to Influenza Virus VariabilitySharma, Jhanvi; Shepardson, Kelly; Johns, Laura L.; Wellham, Julia; Avera, John; Schwarz, Benjamin; Rynda-Apple, Agnieszka; Douglas, TrevorACS Applied Materials & Interfaces (2020), 12 (16), 18211-18224CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)The continuous evolution of influenza A virus (IAV) requires the influenza vaccine formulations to be updated annually to provide adequate protection. Recombinant protein-based vaccines provide safer, faster and a more scalable alternative to the conventional embryonated egg approach for developing vaccines. However, these vaccines are typically poorer in immunogenicity than the vaccines contg. inactivated or attenuated influenza viruses and require administration of a large antigen dosage together with potent adjuvants. Presentation of protein-antigens on the surface of virus-like particles (VLP) provides an attractive strategy to rapidly induce stronger antigen-specific immune responses. Here we have examd. the immunogenic potential and protective efficacy of P22 VLPs conjugated with multiple copies of the globular head domain of the hemagglutinin (HA) protein from the PR8 strain of IAV in a murine model of influenza pathogenesis. Using a covalent attachment strategy (SpyTag/SpyCatcher) we conjugated the HA globular head, which was recombinantly expressed in a genetically modified E. coli strain and found to refold as a monomer, to pre-assembled P22 VLPs. Immunization of mice with this P22-HAhead conjugate provided full protection from morbidity and mortality following infection with a homologous IAV strain. Moreover, the P22-HAhead conjugate also elicited an accelerated and enhanced HA head specific IgG response, which was significantly higher than the sol. HA head, or the admixt. of P22 and HA head without the need for adjuvants. Thus, our results show that the HA head can be easily prepd. by in vitro refolding in a modified E. coli strain, maintaining its intact structure, and enabling the induction of a strong immune response when conjugated to P22 VLPs, even when presented as a monomer. These results also demonstrate that the P22 VLPs can be rapidly modified in a modular fashion resulting in an effective vaccine construct that can generate protective immunity without the need for addnl. adjuvants.
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9Coleman, C. M.; Liu, Y. V.; Mu, H.; Taylor, J. K.; Massare, M.; Flyer, D. C.; Glenn, G. M.; Smith, G. E.; Frieman, M. B. Purified Coronavirus Spike Protein Nanoparticles Induce Coronavirus Neutralizing Antibodies in Mice. Vaccine 2014, 32, 3169– 3174, DOI: 10.1016/j.vaccine.2014.04.0169https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXnsVWltbc%253D&md5=ae9d0bdd54af7796725c5f7c4755e4c9Purified coronavirus spike protein nanoparticles induce coronavirus neutralizing antibodies in miceColeman, Christopher M.; Liu, Ye V.; Mu, Haiyan; Taylor, Justin K.; Massare, Michael; Flyer, David C.; Glenn, Gregory M.; Smith, Gale E.; Frieman, Matthew B.Vaccine (2014), 32 (26), 3169-3174CODEN: VACCDE; ISSN:0264-410X. (Elsevier Ltd.)Development of vaccination strategies for emerging pathogens are particularly challenging because of the sudden nature of their emergence and the long process needed for traditional vaccine development. Therefore, there is a need for development of a rapid method of vaccine development that can respond to emerging pathogens in a short time frame. The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in late 2012 demonstrate the importance of coronaviruses as emerging pathogens. The spike glycoproteins of coronaviruses reside on the surface of the virion and are responsible for virus entry. The spike glycoprotein is the major immunodominant antigen of coronaviruses and has proven to be an excellent target for vaccine designs that seek to block coronavirus entry and promote antibody targeting of infected cells. Vaccination strategies for coronaviruses have involved live attenuated virus, recombinant viruses, non-replicative virus-like particles expressing coronavirus proteins or DNA plasmids expressing coronavirus genes. None of these strategies has progressed to an approved human coronavirus vaccine in the ten years since SARS-CoV emerged. Here we describe a novel method for generating MERS-CoV and SARS-CoV full-length spike nanoparticles, which in combination with adjuvants are able to produce high titer antibodies in mice.
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10Schindewolf, C.; Menachery, V. D. Middle East Respiratory Syndrome Vaccine Candidates: Cautious Optimism. Viruses 2019, 11, 74, DOI: 10.3390/v1101007410https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtlOrtLnL&md5=117ad302d878297978c7e81605ce694aMiddle East respiratory syndrome vaccine candidates: cautious optimismSchindewolf, Craig; Menachery, Vineet D.Viruses (2019), 11 (1), 74CODEN: VIRUBR; ISSN:1999-4915. (MDPI AG)A review. Efforts towards developing a vaccine for Middle East respiratory syndrome coronavirus (MERS-CoV) have yielded promising results. Utilizing a variety of platforms, several vaccine approaches have shown efficacy in animal models and begun to enter clin. trials. In this review, we summarize the current progress towards a MERS-CoV vaccine and highlight potential roadblocks identified from previous attempts to generate coronavirus vaccines.
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11Jung, S.-Y.; Kang, K. W.; Lee, E.-Y.; Seo, D.-W.; Kim, H.-L.; Kim, H.; Kwon, T.; Park, H.-L.; Kim, H.; Lee, S.-M.; Nam, J.-H. Heterologous Prime–Boost Vaccination with Adenoviral Vector and Protein Nanoparticles Induces Both Th1 and Th2 Responses against Middle East Respiratory Syndrome Coronavirus. Vaccine 2018, 36, 3468– 3476, DOI: 10.1016/j.vaccine.2018.04.08211https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXptVCqtrk%253D&md5=10552fd92b8dd1c5d847219fc1edf27fHeterologous prime-boost vaccination with adenoviral vector and protein nanoparticles induces both Th1 and Th2 responses against Middle East respiratory syndrome coronavirusJung, Seo-Yeon; Kang, Kyung Won; Lee, Eun-Young; Seo, Dong-Won; Kim, Hong-Lim; Kim, Hak; Kwon, TaeWoo; Park, Hye-Lim; Kim, Hun; Lee, Sang-Myeong; Nam, Jae-HwanVaccine (2018), 36 (24), 3468-3476CODEN: VACCDE; ISSN:0264-410X. (Elsevier Ltd.)In this study, we developed two types of MERS-CoV vaccines: a recombinant adenovirus serotype 5 encoding the MERS-CoV spike gene (Ad5/MERS) and spike protein nanoparticles formulated with aluminum (alum) adjuvant. Next, we tested a heterologous prime-boost vaccine strategy, which compared priming with Ad5/MERS and boosting with spike protein nanoparticles and vice versa, with homologous prime-boost vaccination comprising priming and boosting with either spike protein nanoparticles or Ad5/MERS. Although both types of vaccine could induce specific IgG against MERS-CoV, neutralizing antibodies against MERS-CoV were induced only by heterologous prime-boost immunization and homologous immunization with spike protein nanoparticles. Heterologous prime-boost vaccination regimens including Ad5/MERS elicited simultaneous Th1 and Th2 responses, but homologous prime-boost regimens did not. Thus, heterologous prime-boost may induce longer-lasting immune responses against MERS-CoV because of an appropriate balance of Th1/Th2 responses. However, both heterologous prime-boost and homologous spike protein nanoparticles vaccinations could provide protection from MERS-CoV challenge in mice. Our results demonstrate that heterologous immunization by priming with Ad5/MERS and boosting with spike protein nanoparticles could be an efficient prophylactic strategy against MERS-CoV infection.
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12Udugama, B.; Kadhiresan, P.; Kozlowski, H. N.; Malekjahani, A.; Osborne, M.; Li, V. Y. C.; Chen, H.; Mubareka, S.; Gubbay, J. B.; Chan, W. C. W. Diagnosing Covid-19: The Disease and Tools for Detection. ACS Nano 2020, 14, 3822– 3835, DOI: 10.1021/acsnano.0c0262412https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXlvFChtrk%253D&md5=0e9ea61666e72862e7587ceb281c5fe4Diagnosing COVID-19: The Disease and Tools for DetectionUdugama, Buddhisha; Kadhiresan, Pranav; Kozlowski, Hannah N.; Malekjahani, Ayden; Osborne, Matthew; Li, Vanessa Y. C.; Chen, Hongmin; Mubareka, Samira; Gubbay, Jonathan B.; Chan, Warren C. W.ACS Nano (2020), 14 (4), 3822-3835CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)A review. COVID-19 has spread globally since its discovery in Hubei province, China in Dec. 2019. A combination of computed tomog. imaging, whole genome sequencing, and electron microscopy were initially used to screen and identify SARS-CoV-2, the viral etiol. of COVID-19. The aim of this review article is to inform the audience of diagnostic and surveillance technologies for SARS-CoV-2 and their performance characteristics. We describe point-of-care diagnostics that are on the horizon and encourage academics to advance their technologies beyond conception. Developing plug-and-play diagnostics to manage the SARS-CoV-2 outbreak would be useful in preventing future epidemics.
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13Yan, R.; Zhang, Y.; Li, Y.; Xia, L.; Guo, Y.; Zhou, Q. Structural Basis for the Recognition of SARS-CoV-2 by Full-Length Human ACE2. Science 2020, 367, 1444– 1448, DOI: 10.1126/science.abb276213https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXlslymsLo%253D&md5=ff4dfdfc646ea878cfb325019160e94aStructural basis for the recognition of SARS-CoV-2 by full-length human ACE2Yan, Renhong; Zhang, Yuanyuan; Li, Yaning; Xia, Lu; Guo, Yingying; Zhou, QiangScience (Washington, DC, United States) (2020), 367 (6485), 1444-1448CODEN: SCIEAS; ISSN:1095-9203. (American Association for the Advancement of Science)Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for severe acute respiratory syndrome coronavirus (SARS-CoV) and the new coronavirus (SARS-CoV-2) that is causing the serious coronavirus disease 2019 (COVID-19) epidemic. Here, we present cryo-electron microscopy structures of full-length human ACE2 in the presence of the neutral amino acid transporter B0AT1 with or without the receptor binding domain (RBD) of the surface spike glycoprotein (S protein) of SARS-CoV-2, both at an overall resoln. of 2.9 angstroms, with a local resoln. of 3.5 angstroms at the ACE2-RBD interface. The ACE2-B0AT1 complex is assembled as a dimer of heterodimers, with the collectrin-like domain of ACE2 mediating homodimerization. The RBD is recognized by the extracellular peptidase domain of ACE2 mainly through polar residues. These findings provide important insights into the mol. basis for coronavirus recognition and infection.
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14Chan, W. C. W. Nano Research for Covid-19. ACS Nano 2020, 14, 3719– 3720, DOI: 10.1021/acsnano.0c0254014https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXlvFeqt7s%253D&md5=11dd55b6b01c0b0ce2b175e2517cbe21Nano Research for COVID-19Chan, Warren C. W.ACS Nano (2020), 14 (4), 3719-3720CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)A review. In the fight against COVID-19, research and technol. development and deployment are our best weapons. Nano-technol. tools can be adapted to detect, to treat, and to prevent this disease. Our community has a chance to accelerate the translation of our developments and deploy nanotechnol. advances as frontline tools.
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15Farka, Z.; Juřík, T.; Kovář, D.; Trnková, L.; Skládal, P. Nanoparticle-Based Immunochemical Biosensors and Assays: Recent Advances and Challenges. Chem. Rev. 2017, 117, 9973– 10042, DOI: 10.1021/acs.chemrev.7b0003715https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXht1eku7bI&md5=061b2561dfd603764c0250ac22c6e7d5Nanoparticle-Based Immunochemical Biosensors and Assays: Recent Advances and ChallengesFarka, Zdenek; Jurik, Tomas; Kovar, David; Trnkova, Libuse; Skladal, PetrChemical Reviews (Washington, DC, United States) (2017), 117 (15), 9973-10042CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review. The authors review the progress achieved during the recent five years in immunochem. biosensors (immunosensors) combined with nanoparticles for enhanced sensitivity. The initial part introduces antibodies as classic recognition elements. The optical sensing part describes fluorescent, luminescent, and surface plasmon resonance systems. Amperometry, voltammetry, and impedance spectroscopy represent electrochem. transducers; electrochemiluminescence with photoelec. conversion constitute widely used combined methods. The transducing options function together with suitable nanoparticles: metallic and metal oxides including magnetic ones, carbon-based nanotubes, graphene variants and luminescent carbon dots, nanocrystals as quantum dots, and photon up-converting particles. These sources merged together provide extreme variability of existing nanoimmunosensing options. Finally, applications in clin. anal. are summarized: markers, tumor cells, and pharmaceuticals; the detection of pathogenic microorganisms, toxic agents, and pesticides in the environmental field and food products.
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16Patra, J. K.; Das, G.; Fraceto, L. F.; Campos, E. V. R.; Rodriguez-Torres, M. d. P.; Acosta-Torres, L. S.; Diaz-Torres, L. A.; Grillo, R.; Swamy, M. K.; Sharma, S.; Habtemariam, S.; Shin, H.-S. Nano Based Drug Delivery Systems: Recent Developments and Future Prospects. J. Nanobiotechnol. 2018, 16, 71, DOI: 10.1186/s12951-018-0392-816https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXjt1OisL4%253D&md5=a097a21379cd48333d81dffd7c57122fNano based drug delivery systems: recent developments and future prospectsPatra, Jayanta Kumar; Das, Gitishree; Fraceto, Leonardo Fernandes; Campos, Estefania Vangelie Ramos; Rodriguez-Torres, Maria Del Pilar; Acosta-Torres, Laura Susana; Diaz-Torres, Luis Armando; Grillo, Renato; Swamy, Mallappa Kumara; Sharma, Shivesh; Habtemariam, Solomon; Shin, Han-SeungJournal of Nanobiotechnology (2018), 16 (), 71/1-71/33CODEN: JNOAAO; ISSN:1477-3155. (BioMed Central Ltd.)A review. Nanomedicine and nano delivery systems are a relatively new but rapidly developing science where materials in the nanoscale range are employed to serve as means of diagnostic tools or to deliver therapeutic agents to specific targeted sites in a controlled manner. Nanotechnol. offers multiple benefits in treating chronic human diseases by site-specific, and target-oriented delivery of precise medicines. Recently, there are a no. of outstanding applications of the nanomedicine (chemotherapeutic agents, biol. agents, immunotherapeutic agents etc.) in the treatment of various diseases. The current review, presents an updated summary of recent advances in the field of nanomedicines and nano based drug delivery systems through comprehensive scrutiny of the discovery and application of nanomaterials in improving both the efficacy of novel and old drugs (e.g., natural products) and selective diagnosis through disease marker mols. The opportunities and challenges of nanomedicines in drug delivery from synthetic/natural sources to their clin. applications are also discussed. In addn., we have included information regarding the trends and perspectives in nanomedicine area.
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17Han, X.; Xu, K.; Taratula, O.; Farsad, K. Applications of Nanoparticles in Biomedical Imaging. Nanoscale 2019, 11, 799– 819, DOI: 10.1039/C8NR07769J17https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXisFyntbjP&md5=745795b26400f75c3ac09cf12bb15367Applications of nanoparticles in biomedical imagingHan, Xiangjun; Xu, Ke; Taratula, Olena; Farsad, KhashayarNanoscale (2019), 11 (3), 799-819CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)An urgent need for early detection and diagnosis of diseases continuously pushes the advancements of imaging modalities and contrast agents. Current challenges remain for fast and detailed imaging of tissue microstructures and lesion characterization that could be achieved via development of nontoxic contrast agents with longer circulation time. Nanoparticle technol. offers this possibility. Here, we review nanoparticle-based contrast agents employed in most common biomedical imaging modalities, including fluorescence imaging, MRI, CT, US, PET and SPECT, addressing their structure related features, advantages and limitations. Furthermore, their applications in each imaging modality are also reviewed using commonly studied examples. Future research will investigate multifunctional nanoplatforms to address safety, efficacy and theranostic capabilities. Nanoparticles as imaging contrast agents have promise to greatly benefit clin. practice.
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18Canaparo, R.; Foglietta, F.; Giuntini, F.; Della Pepa, C.; Dosio, F.; Serpe, L. Recent Developments in Antibacterial Therapy: Focus on Stimuli-Responsive Drug-Delivery Systems and Therapeutic Nanoparticles. Molecules 2019, 24, 1991, DOI: 10.3390/molecules2410199118https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtlemsbvF&md5=f073f7c2edf7816e82e3a707684a7f39Recent developments in antibacterial therapy: focus on stimuli-responsive drug-delivery systems and therapeutic nanoparticlesCanaparo, Roberto; Foglietta, Federica; Giuntini, Francesca; Della Pepa, Carlo; Dosio, Franco; Serpe, LoredanaMolecules (2019), 24 (10), 1991CODEN: MOLEFW; ISSN:1420-3049. (MDPI AG)A review. Conventional drugs used for antibacterial therapy display several limitations. This is not due to antibiotics being ineffective, but rather due to their low bioavailability, limited penetration to sites of infection and the rise of drug-resistant bacteria. Although new delivery systems (e.g., nanoparticles) that are loaded with antibacterial drugs have been designed to overcome these limitations, therapeutic efficacy does not seem to have improved. Against this backdrop, stimuli-responsive antibiotic-loaded nanoparticles and materials with antimicrobial properties (nanoantibiotics) present the ability to enhance therapeutic efficacy, while also reducing drug resistance and side effects. These stimuli can either be exogenous (e.g., light, ultrasound) or endogenous (e.g., pH, variation in redox gradient, enzymes). This promising therapeutic approach relies on advances in materials science and increased knowledge of microorganism growth and biofilm formation. This review provides an overview in the field of antibacterial drug-delivery systems and nanoantibiotics that benefit from a response to specific triggers, and also presents a no. of future prospects.
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19Chen, L.; Liang, J. An Overview of Functional Nanoparticles as Novel Emerging Antiviral Therapeutic Agents. Mater. Sci. Eng., C 2020, 112, 110924, DOI: 10.1016/j.msec.2020.11092419https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXnt1WgsLc%253D&md5=ea6cd71a6a0aefb400c1af8331f8c05eAn overview of functional nanoparticles as novel emerging antiviral therapeutic agentsChen, Lu; Liang, JiangongMaterials Science & Engineering, C: Materials for Biological Applications (2020), 112 (), 110924CODEN: MSCEEE; ISSN:0928-4931. (Elsevier B.V.)A review. Research on highly effective antiviral drugs is essential for preventing the spread of infections and reducing losses. Recently, many functional nanoparticles have been shown to possess remarkable antiviral ability, such as quantum dots, gold and silver nanoparticles, nanoclusters, carbon dots, graphene oxide, silicon materials, polymers and dendrimers. Despite their difference in antiviral mechanism and inhibition efficacy, these functional nanoparticles-based structures have unique features as potential antiviral candidates. In this topical review, we highlight the antiviral efficacy and mechanism of these nanoparticles. Specifically, we introduce various methods for analyzing the viricidal activity of functional nanoparticles and the latest advances in antiviral functional nanoparticles. Furthermore, we systematically describe the advantages and disadvantages of these functional nanoparticles in viricidal applications. Finally, we discuss the challenges and prospects of antiviral nanostructures. This topic review covers 132 papers and will enrich our knowledge about the antiviral efficacy and mechanism of various functional nanoparticles.
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20Park, J.-E.; Kim, K.; Jung, Y.; Kim, J.-H.; Nam, J.-M. Metal Nanoparticles for Virus Detection. ChemNanoMat 2016, 2, 927– 936, DOI: 10.1002/cnma.20160016520https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xhs1CltrvE&md5=af4c982ee1e5180948d3e6902f17a3ccMetal Nanoparticles for Virus DetectionPark, Jeong-Eun; Kim, Keunsuk; Jung, Yoonjae; Kim, Jae-Ho; Nam, Jwa-MinChemNanoMat (2016), 2 (10), 927-936CODEN: CHEMSB; ISSN:2199-692X. (Wiley-VCH Verlag GmbH & Co. KGaA)Viruses are small agents that can infect living creatures and cause harmful diseases. Rapid, sensitive virus detection would be beneficial for public health, and recent studies have shown that nanoparticles may have applications in virus detection. In particular, the unique properties of metal nanoparticles, originating from localized surface plasmons, allow for detection of virus through various methods. Addnl., the high surface-to-vol. ratio and ease of surface modification of these nanoparticles provide advantages for bio-applications. In this Focus Review, we describe currently available and recent advances in virus detection methods with metal nanoparticles. First, we outline several features of traditional virus detection methods and provide a brief explanation of metal nanoparticles. Then, we discuss soln.-based or substrate-based virus detection according to the main operating phase of the detection elements. Finally, we evaluate the use of clin. samples for virus detection with metal nanoparticles.
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21Corman, V. M.; Landt, O.; Kaiser, M.; Molenkamp, R.; Meijer, A.; Chu, D. K.; Bleicker, T.; Brünink, S.; Schneider, J.; Schmidt, M. L.; Mulders, D. G.; Haagmans, B. L.; van der Veer, B.; van den Brink, S.; Wijsman, L.; Goderski, G.; Romette, J.-L.; Ellis, J.; Zambon, M.; Peiris, M.; Goossens, H.; Reusken, C.; Koopmans, M. P.; Drosten, C. Detection of 2019 Novel Coronavirus (2019-nCoV) by Real-Time RT-PCR. Euro Surveill. 2020, 25, 2000045, DOI: 10.2807/1560-7917.ES.2020.25.3.2000045There is no corresponding record for this reference.
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22Shen, M.; Zhou, Y.; Ye, J.; Abdullah Al-Maskri, A. A.; Kang, Y.; Zeng, S.; Cai, S. Recent Advances and Perspectives of Nucleic Acid Detection for Coronavirus. J. Pharm. Anal. 2020, 10, 97– 101, DOI: 10.1016/j.jpha.2020.02.01022https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB38zlsVGgug%253D%253D&md5=345f4c6314a6a890a0b3b365df819d6bRecent advances and perspectives of nucleic acid detection for coronavirusShen Minzhe; Zhou Ying; Ye Jiawei; Abdullah Al-Maskri Abdu Ahmed; Kang Yu; Zeng Su; Cai ShengJournal of pharmaceutical analysis (2020), 10 (2), 97-101 ISSN:.The recent pneumonia outbreak caused by a novel coronavirus (SARS-CoV-2) is posing a great threat to global public health. Therefore, rapid and accurate identification of pathogenic viruses plays a vital role in selecting appropriate treatments, saving people's lives and preventing epidemics. It is important to establish a quick standard diagnostic test for the detection of the infectious disease (COVID-19) to prevent subsequent secondary spread. Polymerase chain reaction (PCR) is regarded as a gold standard test for the molecular diagnosis of viral and bacterial infections with high sensitivity and specificity. Isothermal nucleic acid amplification is considered to be a highly promising candidate method due to its fundamental advantage in quick procedure time at constant temperature without thermocycler operation. A variety of improved or new approaches also have been developed. This review summarizes the currently available detection methods for coronavirus nucleic acid. It is anticipated that this will assist researchers and clinicians in developing better techniques for timely and effective detection of coronavirus infection.
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23Emery, S. L.; Erdman, D. D.; Bowen, M. D.; Newton, B. R.; Winchell, J. M.; Meyer, R. F.; Tong, S.; Cook, B. T.; Holloway, B. P.; McCaustland, K. A.; Rota, P. A.; Bankamp, B.; Lowe, L. E.; Ksiazek, T. G.; Bellini, W. J.; Anderson, L. J. Real-Time Reverse Transcription-Polymerase Chain Reaction Assay for SARS-Associated Coronavirus. Emerging Infect. Dis. 2004, 10, 311– 316, DOI: 10.3201/eid1002.03075923https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXitVSjt7Y%253D&md5=4b670d95bd413a49fd3e2a76f41c85ecReal-time reverse transcription-polymerase chain reaction assay for SARS-associated coronavirusEmery, Shannon L.; Erdman, Dean D.; Bowen, Michael D.; Newton, Bruce R.; Winchell, Jonas M.; Meyer, Richard F.; Tong, Suxiang; Cook, Byron T.; Holloway, Brian P.; McCaustland, Karen A.; Rota, Paul A.; Bankamp, Bettina; Lowe, Luis E.; Ksiazek, Tom G.; Bellini, William J.; Anderson, Larry J.Emerging Infectious Diseases (2004), 10 (2), 311-316CODEN: EIDIFA; ISSN:1080-6040. (National Center for Infectious Diseases, Centers for Disease Control and Prevention)A real-time reverse transcription-polymerase chain reaction (RT-PCR) assay was developed to rapidly detect the severe acute respiratory syndrome-assocd. coronavirus (SARS-CoV). The assay, based on multiple primer and probe sets located in different regions of the SARS-CoV genome, could discriminate SARS-CoV from other human and animal coronaviruses with a potential detection limit of <10 genomic copies per reaction. The real-time RT-PCR assay was more sensitive than a conventional RT-PCR assay or culture isolation and proved suitable to detect SARS-CoV in clin. specimens. Application of this assay will aid in diagnosing SARS-CoV infection.
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24Zhang, Y.; Qu, S.; Xu, L. Progress in the Study of Virus Detection Methods: The Possibility of Alternative Methods to Validate Virus Inactivation. Biotechnol. Bioeng. 2019, 116, 2095– 2102, DOI: 10.1002/bit.2700324https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtVGgsb%252FN&md5=7151503fe2cf3942d85fd0ecfbd402e7Progress in the study of virus detection methods: The possibility of alternative methods to validate virus inactivationZhang, Yu; Qu, Shuxin; Xu, LimingBiotechnology and Bioengineering (2019), 116 (8), 2095-2102CODEN: BIBIAU; ISSN:0006-3592. (John Wiley & Sons, Inc.)Virus inactivation validation studies have been widely applied in the risk assessment of biogenic material-based medical products, such as biol. products, animal tissue-derived biomaterials, and allogeneic biomaterials, to decrease the risk of virus transmission. Traditional virus detection methods in an inactivation validation study utilize cell culture as a tool to quantify the infectious virus by observing cytopathic effects (CPEs) after virus inactivation. However, this is susceptible to subjective factors because CPEs must be obsd. by experts under a microscope during virus titrn. In addn., this method is costly and time- and labor-consuming. Mol. biol. technologies such as quant. polymerase chain reaction (qPCR) have been widely used for virus detection but cannot distinguish infectious and noninfectious viruses. Therefore, qPCR cannot be directly applied to virus inactivation validation studies. In this paper, methods to detect viruses and progress in the challenge of differentiating infectious and noninfectious viruses with the combination of pretreatment and qPCR techniques such as the integrated cell culture-qPCR (ICC-qPCR) method are reviewed. In addn., the advantages and disadvantages of each new method, as well as its prospect in virus inactivation validation studies, are discussed.
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25Fukushi, S.; Fukuma, A.; Kurosu, T.; Watanabe, S.; Shimojima, M.; Shirato, K.; Iwata-Yoshikawa, N.; Nagata, N.; Ohnishi, K.; Ato, M.; Melaku, S. K.; Sentsui, H.; Saijo, M. Characterization of Novel Monoclonal Antibodies against the MERS-Coronavirus Spike Protein and Their Application in Species-Independent Antibody Detection by Competitive Elisa. J. Virol. Methods 2018, 251, 22– 29, DOI: 10.1016/j.jviromet.2017.10.00825https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhs1elur3F&md5=cc5ae2c729927e50904fb962e209c8f8Characterization of novel monoclonal antibodies against the MERS-coronavirus spike protein and their application in species-independent antibody detection by competitive ELISAFukushi, Shuetsu; Fukuma, Aiko; Kurosu, Takeshi; Watanabe, Shumpei; Shimojima, Masayuki; Shirato, Kazuya; Iwata-Yoshikawa, Naoko; Nagata, Noriyo; Ohnishi, Kazuo; Ato, Manabu; Melaku, Simenew Keskes; Sentsui, Hiroshi; Saijo, MasayukiJournal of Virological Methods (2018), 251 (), 22-29CODEN: JVMEDH; ISSN:0166-0934. (Elsevier B.V.)Since discovering the Middle East respiratory syndrome coronavirus (MERS-CoV) as a causative agent of severe respiratory illness in the Middle East in 2012, serol. testing has been conducted to assess antibody responses in patients and to investigate the zoonotic reservoir of the virus. Although the virus neutralization test is the gold std. assay for MERS diagnosis and for investigating the zoonotic reservoir, it uses live virus and so must be performed in high containment labs. Competitive ELISA (cELISA), in which a labeled monoclonal antibody (MAb) competes with test serum antibodies for target epitopes, may be a suitable alternative because it detects antibodies in a species-independent manner. In this study, novel MAbs against the spike protein of MERS-CoV were produced and characterized. One of these MAbs was used to develop a cELISA. The cELISA detected MERS-CoV-specific antibodies in sera from MERS-CoV-infected rats and rabbits immunized with the spike protein of MERS-CoV. The MAb-based cELISA was validated using sera from Ethiopian dromedary camels. Relative to the neutralization test, the cELISA detected MERS-CoV-specific antibodies in 66 Ethiopian dromedary camels with a sensitivity and specificity of 98% and 100%, resp. The cELISA and neutralization test results correlated well (Pearson's correlation coeffs. = 0.71-0.76, depending on the cELISA serum diln.). This cELISA may be useful for MERS epidemiol. investigations on MERS-CoV infection.
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26Mokhtarzadeh, A.; Eivazzadeh-Keihan, R.; Pashazadeh, P.; Hejazi, M.; Gharaatifar, N.; Hasanzadeh, M.; Baradaran, B.; de la Guardia, M. Nanomaterial-Based Biosensors for Detection of Pathogenic Virus. TrAC, Trends Anal. Chem. 2017, 97, 445– 457, DOI: 10.1016/j.trac.2017.10.00526https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhslagtbnE&md5=37de1c8ce7bc63421d640769e8676fafNanomaterial-based biosensors for detection of pathogenic virusMokhtarzadeh, Ahad; Eivazzadeh-Keihan, Reza; Pashazadeh, Paria; Hejazi, Maryam; Gharaatifar, Nasrin; Hasanzadeh, Mohammad; Baradaran, Behzad; de la Guardia, MiguelTrAC, Trends in Analytical Chemistry (2017), 97 (), 445-457CODEN: TTAEDJ; ISSN:0165-9936. (Elsevier B.V.)Viruses are real menace to human safety that cause devastating viral disease. The high prevalence of these diseases is due to improper detecting tools. Therefore, there is a remarkable demand to identify viruses in a fast, selective and accurate way. Several biosensors have been designed and commercialized for detection of pathogenic viruses. However, they present many challenges. Nanotechnol. overcomes these challenges and performs direct detection of mol. targets in real time. In this overview, studies concerning nanotechnol.-based biosensors for pathogenic virus detection have been summarized, paying special attention to biosensors based on graphene oxide, silica, carbon nanotubes, gold, silver, zinc oxide and magnetic nanoparticles, which could pave the way to detect viral diseases and provide healthy life for infected patients.
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27Li, H.; Rothberg, L. Colorimetric Detection of DNA Sequences Based on Electrostatic Interactions with Unmodified Gold Nanoparticles. Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 14036– 14039, DOI: 10.1073/pnas.040611510127https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXosVylsrY%253D&md5=c63574b39b9b5b82007779183959a55bColorimetric detection of DNA sequences based on electrostatic interactions with unmodified gold nanoparticlesLi, Huixiang; Rothberg, LewisProceedings of the National Academy of Sciences of the United States of America (2004), 101 (39), 14036-14039CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)We find that single- and double-stranded oligonucleotides have different propensities to adsorb on gold nanoparticles in colloidal soln. We use this observation to design a hybridization assay based on color changes assocd. with gold aggregation. Because the underlying adsorption mechanism is electrostatic, no covalent functionalization of the gold, the probe, or the target DNA is required. Hybridization conditions can be optimized because it is completely sepd. from the detection step. The assay is complete within 5 min, and < 100 fmol of target produces color changes observable without instrumentation. Single-base-pair mismatches are easily detected.
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28Kim, H.; Park, M.; Hwang, J.; Kim, J. H.; Chung, D.-R.; Lee, K.-s.; Kang, M. Development of Label-Free Colorimetric Assay for MERS-CoV Using Gold Nanoparticles. ACS Sens. 2019, 4, 1306– 1312, DOI: 10.1021/acssensors.9b0017528https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXovVKmsL0%253D&md5=8b0c7c510447ec91d809317e915ffddaDevelopment of Label-Free Colorimetric Assay for MERS-CoV Using Gold NanoparticlesKim, Hanbi; Park, Minseon; Hwang, Joonki; Kim, Jin Hwa; Chung, Doo-Ryeon; Lee, Kyu-sung; Kang, MinheeACS Sensors (2019), 4 (5), 1306-1312CODEN: ASCEFJ; ISSN:2379-3694. (American Chemical Society)Worldwide outbreaks of infectious diseases necessitate the development of rapid and accurate diagnostic methods. Colorimetric assays are a representative tool to simply identify the target mols. in specimens through color changes of an indicator (e.g., nanosized metallic particle, and dye mols.). The detection method is used to confirm the presence of biomarkers visually and measure absorbance of the colored compds. at a specific wavelength. In this study, we propose a colorimetric assay based on an extended form of double-stranded DNA (dsDNA) self-assembly shielded gold nanoparticles (AuNPs) under pos. electrolyte (e.g., 0.1 M MgCl2) for detection of Middle East respiratory syndrome coronavirus (MERS-CoV). This platform is able to verify the existence of viral mols. through a localized surface plasmon resonance (LSPR) shift and color changes of AuNPs in the UV-vis wavelength range. We designed a pair of thiol-modified probes at either the 5' end or 3' end to organize complementary base pairs with upstream of the E protein gene (upE) and open reading frames (ORF) 1a on MERS-CoV. The dsDNA of the target and probes forms a disulfide-induced long self-assembled complex, which protects AuNPs from salt-induced aggregation and transition of optical properties. This colorimetric assay could discriminate down to 1 pmol/μL of 30 bp MERS-CoV and further be adapted for convenient on-site detection of other infectious diseases, esp. in resource-limited settings.
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29Huang, P.; Wang, H.; Cao, Z.; Jin, H.; Chi, H.; Zhao, J.; Yu, B.; Yan, F.; Hu, X.; Wu, F.; Jiao, C.; Hou, P.; Xu, S.; Zhao, Y.; Feng, N.; Wang, J.; Sun, W.; Wang, T.; Gao, Y.; Yang, S.; Xia, X. A Rapid and Specific Assay for the Detection of MERS-CoV. Front. Microbiol. 2018, 9, 1101, DOI: 10.3389/fmicb.2018.0110129https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1Mbms12itg%253D%253D&md5=ffdd4aeb8606a2047bda6e5a10536e6aA Rapid and Specific Assay for the Detection of MERS-CoVHuang Pei; Hu Xingxing; Xu Shengnan; Wang Jianzhong; Huang Pei; Wang Hualei; Cao Zengguo; Jin Hongli; Chi Hang; Yan Feihu; Hu Xingxing; Wu Fangfang; Jiao Cuicui; Hou Pengfei; Xu Shengnan; Zhao Yongkun; Feng Na; Sun Weiyang; Wang Tiecheng; Gao Yuwei; Yang Songtao; Xia Xianzhu; Wang Hualei; Cao Zengguo; Jin Hongli; Hou Pengfei; Wang Hualei; Zhao Yongkun; Feng Na; Sun Weiyang; Wang Tiecheng; Gao Yuwei; Yang Songtao; Xia Xianzhu; Zhao Jincun; Zhao Jincun; Yu BeibeiFrontiers in microbiology (2018), 9 (), 1101 ISSN:1664-302X.Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel human coronavirus that can cause human respiratory disease. The development of a detection method for this virus that can lead to rapid and accurate diagnosis would be significant. In this study, we established a nucleic acid visualization technique that combines the reverse transcription loop-mediated isothermal amplification technique and a vertical flow visualization strip (RT-LAMP-VF) to detect the N gene of MERS-CoV. The RT-LAMP-VF assay was performed in a constant temperature water bath for 30 min, and the result was visible by the naked eye within 5 min. The RT-LAMP-VF assay was capable of detecting 2 × 10(1) copies/μl of synthesized RNA transcript and 1 × 10(1) copies/μl of MERS-CoV RNA. The method exhibits no cross-reactivities with multiple CoVs including SARS-related (SARSr)-CoV, HKU4, HKU1, OC43 and 229E, and thus exhibits high specificity. Compared to the real-time RT-PCR (rRT-PCR) method recommended by the World Health Organization (WHO), the RT-LAMP-VF assay is easy to handle, does not require expensive equipment and can rapidly complete detection within 35 min.
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30Moitra, P.; Alafeef, M.; Dighe, K.; Frieman, M. B.; Pan, D. Selective Naked-Eye Detection of SARS-CoV-2 Mediated by N Gene Targeted Antisense Oligonucleotide Capped Plasmonic Nanoparticles. ACS Nano 2020, 14, 7617– 7627, DOI: 10.1021/acsnano.0c0382230https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXpvVGktLc%253D&md5=6edff96bd5fecfeac6bb14b777f4c066Selective Naked-Eye Detection of SARS-CoV-2 Mediated by N Gene Targeted Antisense Oligonucleotide Capped Plasmonic NanoparticlesMoitra, Parikshit; Alafeef, Maha; Dighe, Ketan; Frieman, Matthew B.; Pan, DipanjanACS Nano (2020), 14 (6), 7617-7627CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)The current outbreak of the pandemic coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) demands its rapid, convenient, and large-scale diagnosis to downregulate its spread within as well as across the communities. But the reliability, reproducibility, and selectivity of majority of such diagnostic tests fail when they are tested either to a viral load at its early representation or to a viral gene mutated during its current spread. In this regard, a selective "naked-eye" detection of SARS-CoV-2 is highly desirable, which can be tested without accessing any advanced instrumental techniques. We herein report the development of a colorimetric assay based on gold nanoparticles (AuNPs), when capped with suitably designed thiol-modified antisense oligonucleotides (ASOs) specific for N-gene (nucleocapsid phosphoprotein) of SARS-CoV-2, could be used for diagnosing pos. COVID-19 cases within 10 min from the isolated RNA samples. The thiol-modified ASO-capped AuNPs agglomerate selectively in the presence of its target RNA sequence of SARS-CoV-2 and demonstrate a change in its surface plasmon resonance. Further, the addn. of RNaseH cleaves the RNA strand from the RNA-DNA hybrid leading to a visually detectable ppt. from the soln. mediated by the addnl. agglomeration among the AuNPs. The selectivity of the assay has been monitored in the presence of MERS-CoV viral RNA with a limit of detection of 0.18 ng/μL of RNA having SARS-CoV-2 viral load. Thus, the current study reports a selective and visual "naked-eye" detection of COVID-19 causative virus, SARS-CoV-2, without the requirement of any sophisticated instrumental techniques.
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31Layqah, L. A.; Eissa, S. An Electrochemical Immunosensor for the Corona Virus Associated with the Middle East Respiratory Syndrome Using an Array of Gold Nanoparticle-Modified Carbon Electrodes. Microchim. Acta 2019, 186, 224, DOI: 10.1007/s00604-019-3345-5There is no corresponding record for this reference.
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32Lee, Y.; Kang, B.-H.; Kang, M.; Chung, D. R.; Yi, G.-S.; Lee, L. P.; Jeong, K.-H. Nanoplasmonic on-Chip PCR for Rapid Precision Molecular Diagnostics. ACS Appl. Mater. Interfaces 2020, 12, 12533– 12540, DOI: 10.1021/acsami.9b2359132https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXjvVGltr4%253D&md5=8c15061f8e85afa6a82e86b47cb40866Nanoplasmonic on-Chip PCR for rapid precision molecular diagnosticsLee, Youngseop; Kang, Byoung-Hoon; Kang, Minhee; Chung, Doo Ryeon; Yi, Gwan-Su; Lee, Luke P.; Jeong, Ki-HunACS Applied Materials & Interfaces (2020), 12 (11), 12533-12540CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Emerging mol. diagnosis requires ultrafast polymerase chain reaction (PCR) on chip for rapid precise detection of infectious diseases in the point-of-care test. Here, we report nanoplasmonic on-chip PCR for rapid precision mol. diagnostics. The nanoplasmonic pillar arrays (NPA) comprise gold nanoislands on the top and sidewall of large-scale glass nanopillar arrays. The nanoplasmonic pillars enhance light absorption of a white light-emitting diode (LED) over the whole visible range due to strong electromagnetic hotspots between the nanoislands. As a result, they effectively induce photothermal heating for ultrafast PCR thermal cycling. The temp. profile of NPA exhibits 30 cycles between 98 and 60°C for a total of 3 min and 30 s during the cyclic excitation of white LED light. The exptl. results also demonstrate the rapid DNA amplification of both 0.1 ng μL-1 of λ-DNA in 20 thermal cycles and 0.1 ng μL-1 of complementary DNA of Middle East respiratory syndrome coronavirus in 30 thermal cycles using a conventional PCR vol. of 15μL. This nanoplasmonic PCR technique provides a new opportunity for rapid precision mol. diagnostics.
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33Teengam, P.; Siangproh, W.; Tuantranont, A.; Vilaivan, T.; Chailapakul, O.; Henry, C. S. Multiplex Paper-Based Colorimetric DNA Sensor Using Pyrrolidinyl Peptide Nucleic Acid-Induced AgNPs Aggregation for Detecting MERS-CoV, MTB, and HPV Oligonucleotides. Anal. Chem. 2017, 89, 5428– 5435, DOI: 10.1021/acs.analchem.7b0025533https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXlvVGkt7Y%253D&md5=804791a1596c35f834173a36be8eefc1Multiplex Paper-Based Colorimetric DNA Sensor Using Pyrrolidinyl Peptide Nucleic Acid-Induced AgNPs Aggregation for Detecting MERS-CoV, MTB, and HPV OligonucleotidesTeengam, Prinjaporn; Siangproh, Weena; Tuantranont, Adisorn; Vilaivan, Tirayut; Chailapakul, Orawon; Henry, Charles S.Analytical Chemistry (Washington, DC, United States) (2017), 89 (10), 5428-5435CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)The development of simple fluorescent and colorimetric assays that enable point-of-care DNA and RNA detection has been a topic of significant research because of the utility of such assays in resource limited settings. The most common motifs utilize hybridization to a complementary detection strand coupled with a sensitive reporter mol. Here, a paper-based colorimetric assay for DNA detection based on pyrrolidinyl peptide nucleic acid (acpcPNA)-induced nanoparticle aggregation is reported as an alternative to traditional colorimetric approaches. PNA probes are an attractive alternative to DNA and RNA probes because they are chem. and biol. stable, easily synthesized, and hybridize efficiently with the complementary DNA strands. The acpcPNA probe contains a single pos. charge from the lysine at C-terminus and causes aggregation of citrate anion-stabilized silver nanoparticles (AgNPs) in the absence of complementary DNA. In the presence of target DNA, formation of the anionic DNA-acpcPNA duplex results in dispersion of the AgNPs as a result of electrostatic repulsion, giving rise to a detectable color change. Factors affecting the sensitivity and selectivity of this assay were investigated, including ionic strength, AgNP concn., PNA concn., and DNA strand mismatches. The method was used for screening of synthetic Middle East respiratory syndrome coronavirus (MERS-Co-V), mycobacterium tuberculosis (MTB) and human papillomavirus (HPV)DNA based on a colorimetric paper-based anal. device developed using the aforementioned principle. The oligonucleotide targets were detected by measuring the color change of AgNPs, giving detection limits of 1.53 nM (MERS-Co-V), 1.27 nM (MTB) and 1.03 nM (HPV). The acpcPNA probe exhibited high selectivity for the complementary oligonucleotides over single-base-mismatch, two-base-mismatch and noncomplementary DNA targets. The proposed paper-based colorimetric DNA sensor has potential to be an alternative approach for simple, rapid, sensitive and selective DNA detection.
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34Gong, P.; He, X.; Wang, K.; Tan, W.; Xie, W.; Wu, P.; Li, H. Combination of Functionalized Nanoparticles and Polymerase Chain Reaction-Based Method for SARS-CoV Gene Detection. J. Nanosci. Nanotechnol. 2008, 8, 293– 300, DOI: 10.1166/jnn.2008.1813034https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXnsVamuro%253D&md5=50c4b12d716b46a58c9bbde0c8c54b9aCombination of functionalized nanoparticles and polymerase chain reaction-based method for SARS-CoV gene detectionGong, Ping; He, Xiaoxiao; Wang, Kemin; Tan, Weihong; Xie, Wengang; Wu, Ping; Li, HuiminJournal of Nanoscience and Nanotechnology (2008), 8 (1), 293-300CODEN: JNNOAR; ISSN:1533-4880. (American Scientific Publishers)Rapid and sensitive detection of SARS assocd. coronavirus is crit. for early diagnosis and control of severe acute respiratory syndrome. This study describes a method for the detection of SARS assocd. coronavirus gene by the combination of functionalized nanoparticles and PCR-based assay. In this method, the target cDNA of SARS assocd. coronavirus was firstly captured and enriched from the mixt. of target cDNA and non-target cDNA by the use of the functionalized silica coated superparamagnetic nanoparticles. Addnl., the enriched target cDNA were amplified through a general symmetry PCR and then was selectively isolated from the double strands PCR products by applying the silica coated superparamagnetic nanoparticles again. Finally, we detected the amplified target cDNA by employing the functionalized silica coated fluorescent nanoparticles as signaling probes with a sandwich hybridization format. The results show that the target cDNA can be assayed successfully with a detection limit of 2.0 × 103 copies and the nonspecific amplification could be inhibited. In addn., the detection procedure is rapid and can be completed in less than 6 h. Our results suggest that this approach will provide promising prospects for other pathogens detection.
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35Zhao, Z.; Cui, H.; Song, W.; Ru, X.; Zhou, W.; Yu, X. A Simple Magnetic Nanoparticles-Based Viral RNA Extraction Method for Efficient Detection of SARS-CoV-2. BioRxiv 2020.There is no corresponding record for this reference.
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36Roh, C.; Jo, S. K. Quantitative and Sensitive Detection of SARS Coronavirus Nucleocapsid Protein Using Quantum Dots-Conjugated RNA Aptamer on Chip. J. Chem. Technol. Biotechnol. 2011, 86, 1475– 1479, DOI: 10.1002/jctb.272136https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhsVCnur%252FP&md5=9668cddb8cf8245fc558f83f3b44e426Quantitative and sensitive detection of SARS coronavirus nucleocapsid protein using quantum dots-conjugated RNA aptamer on chipRoh, Changhyun; Jo, Sung KeeJournal of Chemical Technology and Biotechnology (2011), 86 (12), 1475-1479CODEN: JCTBED; ISSN:0268-2575. (John Wiley & Sons Ltd.)Globally, severe acute respiratory syndrome coronavirus (SARS-CoV) is a newly emerging virus that causes SARS with high mortality rate in infected people. The nucleocapsid (N) protein of the severe acute respiratory syndrome (SARS)-assocd. coronavirus (SARS-CoV) is an important antigen for the early diagnosis of SARS and the detection of diseases. Here, a new quantum dots (QDs)-conjugated RNA aptamer with high sensitivity and rapidity is proposed for the detection of SARS-CoV N protein using an on chip system. A QDs-conjugated RNA aptamer can specifically hybridize on the immobilized SARS-CoV N protein on the surface of a glass chip. Detection is based on the optical signal variation of a QDs-supported RNA aptamer interacting on an immobilized protein chip. Using an optical QDs-based RNA aptamer chip, SARS N protein was detected at concns. as low as 0.1 pg mL-1. It was demonstrated that the QDs-conjugated RNA aptamer could interact on a designed chip specifically and sensitively. This device could form a QDs-conjugated biosensor prototype chip for SARS-CoV N protein diagnosis. The proposed visual SARS-CoV N protein detection technique may avoid the limitations of other reported methods because of its high sensitivity, good specificity, ease of use, and the ability to perform one-spot monitoring.
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37Ahmed, S. R.; Nagy, É.; Neethirajan, S. Self-Assembled Star-Shaped Chiroplasmonic Gold Nanoparticles for an Ultrasensitive Chiro-Immunosensor for Viruses. RSC Adv. 2017, 7, 40849– 40857, DOI: 10.1039/C7RA07175B37https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhsVers7zN&md5=1a4acbe1b3f14d5e1df0e41dcb264838Self-assembled star-shaped chiroplasmonic gold nanoparticles for an ultrasensitive chiro-immunosensor for virusesAhmed, Syed Rahin; Nagy, Eva; Neethirajan, SureshRSC Advances (2017), 7 (65), 40849-40857CODEN: RSCACL; ISSN:2046-2069. (Royal Society of Chemistry)Near field optics and optical tunneling light-matter interactions in the superstructure of chiral nanostructures and semiconductor quantum dots exhibit strong optical rotation activity that may open a new window for chiral-based bioanalyte detection. Herein we report an ultrasensitive, chiro-immunosensor using a superstructure of chiral gold nanohybrids (CAu NPs) and quantum dots (QDs). Self-assembly techniques were employed to create asym. plasmonic chiral nanostructures to extend the spectral range of the CD (CD) response to obtain superior plasmonic resonant coupling with the QD excited state; this may help to achieve lower limit of detection (LOD) values. As a result, the designed probe could detect avian influenza A (H5N1) viral concns. at the picomolar level, a significant improvement in sensitivity in comparison to a non-assembled CAu NP-based chiro-assay. The practicability of the proposed sensing system was successfully demonstrated on several virus cultures, including avian influenza A (H4N6) virus, fowl adenovirus and coronavirus in blood samples. The results of our study highlight that exciton-plasmon interactions change the chirality, and the use of self-assembled nanostructures is an efficient strategy for enhancing the sensitivity of plasmonic nanosensors.
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38Ahmed, S. R.; Kang, S. W.; Oh, S.; Lee, J.; Neethirajan, S. Chiral Zirconium Quantum Dots: A New Class of Nanocrystals for Optical Detection of Coronavirus. Heliyon 2018, 4, e00766, DOI: 10.1016/j.heliyon.2018.e00766There is no corresponding record for this reference.
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39Fong, K. E.; Yung, L. -Y. L. Localized Surface Plasmon Resonance: A Unique Property of Plasmonic Nanoparticles for Nucleic Acid Detection. Nanoscale 2013, 5, 12043– 12071, DOI: 10.1039/c3nr02257a39https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhvVejurfI&md5=e47a2ed4060bd96422cbbad858226deeLocalized surface plasmon resonance: a unique property of plasmonic nanoparticles for nucleic acid detectionFong, Kah Ee; Yung, Lin-Yue LanryNanoscale (2013), 5 (24), 12043-12071CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)A review. Localized surface plasmon resonance (LSPR) of noble metal nanoparticles (a.k.a. plasmonic nanoparticles) opens up a new horizon for advanced biomol. sensing. However, an effective and practical sensing system still requires meticulous design to achieve good sensitivity and distinctive selectivity for routine use and high-throughput detection. In particular, the detection of DNA and RNA is crucial in biomedical research and clin. diagnostics. This review describes the fundamental aspects of LSPR and provides an overall account of how it is exploited to assist in nucleic acid sensing. The detection efficiency of each LSPR-based approach is assessed with respect to the assay design, the selection of plasmonic nanoparticles, and the choice of nucleic acid probes which influence the duplex hybridization. Judicious comparison is made among various LSPR-based approaches in terms of the assaying time, the sensitivity or lowest sensing concn. (i.e. limit of detection or LOD), and the single-base mismatch (SBM) selectivity.
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40Unser, S.; Bruzas, I.; He, J.; Sagle, L. Localized Surface Plasmon Resonance Biosensing: Current Challenges and Approaches. Sensors 2015, 15, 15684– 15716, DOI: 10.3390/s15071568440https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC28%252FgslGhtg%253D%253D&md5=32c09c56423b729c1928124f8300131fLocalized Surface Plasmon Resonance Biosensing: Current Challenges and ApproachesUnser Sarah; Bruzas Ian; He Jie; Sagle LauraSensors (Basel, Switzerland) (2015), 15 (7), 15684-716 ISSN:.Localized surface plasmon resonance (LSPR) has emerged as a leader among label-free biosensing techniques in that it offers sensitive, robust, and facile detection. Traditional LSPR-based biosensing utilizes the sensitivity of the plasmon frequency to changes in local index of refraction at the nanoparticle surface. Although surface plasmon resonance technologies are now widely used to measure biomolecular interactions, several challenges remain. In this article, we have categorized these challenges into four categories: improving sensitivity and limit of detection, selectivity in complex biological solutions, sensitive detection of membrane-associated species, and the adaptation of sensing elements for point-of-care diagnostic devices. The first section of this article will involve a conceptual discussion of surface plasmon resonance and the factors affecting changes in optical signal detected. The following sections will discuss applications of LSPR biosensing with an emphasis on recent advances and approaches to overcome the four limitations mentioned above. First, improvements in limit of detection through various amplification strategies will be highlighted. The second section will involve advances to improve selectivity in complex media through self-assembled monolayers, "plasmon ruler" devices involving plasmonic coupling, and shape complementarity on the nanoparticle surface. The following section will describe various LSPR platforms designed for the sensitive detection of membrane-associated species. Finally, recent advances towards multiplexed and microfluidic LSPR-based devices for inexpensive, rapid, point-of-care diagnostics will be discussed.
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41Srinoi, P.; Chen, Y.-T.; Vittur, V.; Marquez, M. D.; Lee, T. R. Bimetallic Nanoparticles: Enhanced Magnetic and Optical Properties for Emerging Biological Applications. Appl. Sci. 2018, 8, 1106, DOI: 10.3390/app807110641https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhs1OgurnL&md5=258dcac5900eaf8f3bc9bd44e2a13855Bimetallic nanoparticles: enhanced magnetic and optical properties for emerging biological applicationsSrinoi, Pannaree; Chen, Yi-Ting; Vittur, Varadee; Marquez, Maria D.; Lee, T. RandallApplied Sciences (2018), 8 (7), 1106/1-1106/32CODEN: ASPCC7; ISSN:2076-3417. (MDPI AG)Metal nanoparticles are extensively studied due to their unique chem. and phys. properties, which differ from the properties of their resp. bulk materials. Likewise, the properties of heterogeneous bimetallic structures are far more attractive than those of single-component nanoparticles. For example, the incorporation of a second metal into a nanoparticle structure influences and can potentially enhance the optical/plasmonic and magnetic properties of the material. This review focuses on the enhanced optical/plasmonic and magnetic properties offered by bimetallic nanoparticles and their corresponding impact on biol. applications. In this review, we summarize the predominant structures of bimetallic nanoparticles, outline their synthesis methods, and highlight their use in biol. applications, both diagnostic and therapeutic, which are dictated by their various optical/plasmonic and magnetic properties.
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42Draz, M. S.; Shafiee, H. Applications of Gold Nanoparticles in Virus Detection. Theranostics 2018, 8, 1985– 2017, DOI: 10.7150/thno.2385642https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXit1Srtb7O&md5=75ecce9d6b9e1b25661750fcfe1251a9Applications of gold nanoparticles in virus detectionDraz, Mohamed Shehata; Shafiee, HadiTheranostics (2018), 8 (7), 1985-2017CODEN: THERDS; ISSN:1838-7640. (Ivyspring International Publisher)A review. Viruses are the smallest known microbes, yet they cause the most significant losses in human health. Most of the time, the best-known cure for viruses is the innate immunol. defense system of the host; otherwise, the initial prevention of viral infection is the only alternative. Therefore, diagnosis is the primary strategy toward the overarching goal of virus control and elimination. The introduction of a new class of nanoscale materials with multiple unique properties and functions has sparked a series of breakthrough applications. Gold nanoparticles (AuNPs) are widely reported to guide an impressive resurgence in biomedical and diagnostic applications. Here, we the applications of AuNPs in virus testing and detection. The developed AuNP-based detection techniques are reported for various groups of clin. relevant viruses with a special focus on the applied types of bio-AuNP hybrid structures, virus detection targets, and assay modalities and formats. We pay particular attention to highlighting the functional role and activity of each core Au nanostructure and the resultant detection improvements in terms of sensitivity, detection range, and time. In addn., we provide a general summary of the contributions of AuNPs to the mainstream methods of virus detection, tech. measures, and recommendations required in guidance toward com. in-field applications.
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43Dykman, L. A.; Khlebtsov, N. G. Gold Nanoparticles in Biology and Medicine: Recent Advances and Prospects. Acta Naturae 2011, 3, 34– 55, DOI: 10.32607/20758251-2011-3-2-34-5543https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC38nns12htQ%253D%253D&md5=51943c1089c3d109b251a85db98a067eGold nanoparticles in biology and medicine: recent advances and prospectsDykman L A; Khlebtsov N GActa naturae (2011), 3 (2), 34-55 ISSN:2075-8251.Functionalized gold nanoparticles with controlled geometrical and optical properties are the subject of intensive studies and biomedical applications, including genomics, biosensorics, immunoassays, clinical chemistry, laser phototherapy of cancer cells and tumors, the targeted delivery of drugs, DNA and antigens, optical bioimaging and the monitoring of cells and tissues with the use of state-of-the-art detection systems. This work will provide an overview of the recent advances and current challenges facing the biomedical application of gold nanoparticles of various sizes, shapes, and structures. The review is focused on the application of gold nanoparticle conjugates in biomedical diagnostics and analytics, photothermal and photodynamic therapies, as a carrier for delivering target molecules, and on the immunological and toxicological properties. Keeping in mind the huge volume and high speed of the data update rate, 2/3 of our reference list (certainly restricted to 250 Refs.) includes publications encompassing the past 5 years.
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44Khan, M. S.; Vishakante, G. D.; Siddaramaiah, H. Gold Nanoparticles: A Paradigm Shift in Biomedical Applications. Adv. Colloid Interface Sci. 2013, 199–200, 44– 58, DOI: 10.1016/j.cis.2013.06.00344https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtFamurjI&md5=aeb544809e0b8a37e30744614716c72cGold nanoparticles: A paradigm shift in biomedical applicationsKhan, Mohammed S.; Vishakante, Gowda D.; Siddaramaiah HAdvances in Colloid and Interface Science (2013), 199-200 (), 44-58CODEN: ACISB9; ISSN:0001-8686. (Elsevier B.V.)A review. In the medical field, majority of the active ingredients exists in the form of solid particle (90% of all medicines). Nanotechnol. had grabbed the attention of many scientists working in different aspects and gave them a vivid imagination in order to utilize the nanotechnol. in an innovative way according to their needs. One of the major applications of nanotechnol. is drug delivery through nanoparticles which is on boom for the researchers and gives a challenging environment for the researchers. Among them upcoming challenge is the use of inorg. nanoparticles for the drug delivery and related aspects. There is growing interests in usage of inorg. nanoparticles in medicine due to their size, and unique phys. properties that make them different from other nanoparticulate systems. This review will lay special emphasis on the uniqueness of inorg. nanoparticles esp. gold nanoparticles as a drug delivery vehicle and moreover will present a wide spread scenario of gold nanoparticles that has been used for treatment of life threatening diseases like cancer.
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45Ghosh, S. K.; Pal, T. Interparticle Coupling Effect on the Surface Plasmon Resonance of Gold Nanoparticles: From Theory to Applications. Chem. Rev. 2007, 107, 4797– 4862, DOI: 10.1021/cr068028245https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXht1yrt7zK&md5=9ce7a095da187d983856f61cec8e9618Interparticle Coupling Effect on the Surface Plasmon Resonance of Gold Nanoparticles: From Theory to ApplicationsGhosh, Sujit Kumar; Pal, TarasankarChemical Reviews (Washington, DC, United States) (2007), 107 (11), 4797-4862CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review. This article presents the varieties in synthetic strategies and characterization of nanoscale gold particles assembled into an aggregate structure.
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46Qiu, G.; Gai, Z.; Tao, Y.; Schmitt, J.; Kullak-Ublick, G. A.; Wang, J. Dual-Functional Plasmonic Photothermal Biosensors for Highly Accurate Severe Acute Respiratory Syndrome Coronavirus 2 Detection. ACS Nano 2020, 14, 5268– 5277, DOI: 10.1021/acsnano.0c0243946https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXmvVCksr8%253D&md5=49fd6f805d926ee5e95a72763d574e4cDual-Functional Plasmonic Photothermal Biosensors for Highly Accurate Severe Acute Respiratory Syndrome Coronavirus 2 DetectionQiu, Guangyu; Gai, Zhibo; Tao, Yile; Schmitt, Jean; Kullak-Ublick, Gerd A.; Wang, JingACS Nano (2020), 14 (5), 5268-5277CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)The ongoing outbreak of the novel coronavirus disease (COVID-19) has spread globally and poses a threat to public health in more than 200 countries. Reliable lab. diagnosis of the disease has been one of the foremost priorities for promoting public health interventions. The routinely used reverse transcription polymerase chain reaction (RT-PCR) is currently the ref. method for COVID-19 diagnosis. However, it also reported a no. of false-pos. or -neg. cases, esp. in the early stages of the novel virus outbreak. In this work, a dual-functional plasmonic biosensor combining the plasmonic photothermal (PPT) effect and localized surface plasmon resonance (LSPR) sensing transduction provides an alternative and promising soln. for the clin. COVID-19 diagnosis. The two-dimensional gold nanoislands (AuNIs) functionalized with complementary DNA receptors can perform a sensitive detection of the selected sequences from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through nucleic acid hybridization. For better sensing performance, the thermoplasmonic heat is generated on the same AuNIs chip when illuminated at their plasmonic resonance frequency. The localized PPT heat is capable to elevate the in situ hybridization temp. and facilitate the accurate discrimination of two similar gene sequences. Our dual-functional LSPR biosensor exhibits a high sensitivity toward the selected SARS-CoV-2 sequences with a lower detection limit down to the concn. of 0.22 pM and allows precise detection of the specific target in a multigene mixt. This study gains insight into the thermoplasmonic enhancement and its applicability in the nucleic acid tests and viral disease diagnosis.
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47Ma, C.; Li, C.; Wang, F.; Ma, N.; Li, X.; Li, Z.; Deng, Y.; Wang, Z.; Xi, Z.; Tang, Y.; He, N. Magnetic Nanoparticles-Based Extraction and Verification of Nucleic Acids from Different Sources. J. Biomed. Nanotechnol. 2013, 9, 703– 709, DOI: 10.1166/jbn.2013.156647https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXltlGqsLg%253D&md5=6b92896860978ae34dde64b9789f42bdMagnetic nanoparticles-based extraction and verification of nucleic acids from different sourcesMa, Chao; Li, Chuanyan; Wang, Fang; Ma, Ningning; Li, Xiaolong; Li, Zhiyang; Deng, Yan; Wang, Zhifei; Xi, Zhijiang; Tang, Yongjun; He, NongyueJournal of Biomedical Nanotechnology (2013), 9 (4), 703-709CODEN: JBNOAB; ISSN:1550-7033. (American Scientific Publishers)In many mol. biol. and genetic technol. studies, the amt. of available DNA can be one of the important criteria for selecting the samples from different sources. Compared with those genomic DNA methods using org. solvents or other traditional com. kits, the method based on magnetic nanoparticles (MNPs) and adsorption technol. has many remarkable advantages like being time-saving and cost effective without the laborious centrifugation or pptn. steps, and more importantly it has the great potential and esp. suitable for automated DNA extn. and up-scaling. In this paper, the extn. efficiency of genomic nucleic acids based on magnetic nanoparticles from four different sources including bacteria, yeast, human blood and virus samples are compared and verified. After measurement and verification of the extd. genomic nucleic acids, it was shown that all these genomic nucleic acids extd. using the MNPs method can be of high yield and be available for next mol. biol. steps.
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48Borlido, L.; Azevedo, A. M.; Roque, A. C.; Aires-Barros, M. R. Magnetic Separations in Biotechnology. Biotechnol. Adv. 2013, 31, 1374– 1385, DOI: 10.1016/j.biotechadv.2013.05.00948https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtVWlsr%252FI&md5=c103af906cf437b04ce71ade5c66c223Magnetic separations in biotechnologyBorlido, L.; Azevedo, A. M.; Roque, A. C. A.; Aires-Barros, M. R.Biotechnology Advances (2013), 31 (8), 1374-1385CODEN: BIADDD; ISSN:0734-9750. (Elsevier)A review. Magnetic sepns. are probably one of the most versatile sepn. processes in biotechnol. as they are able to purify cells, viruses, proteins and nucleic acids directly from crude samples. The fast and gentle process in combination with its easy scale-up and automation provide unique advantages over other sepn. techniques. In the midst of this process are the magnetic adsorbents tailored for the envisioned target and whose complex synthesis spans over multiple fields of science. In this context, this article reviews both the synthesis and tailoring of magnetic adsorbents for biosepns. as well as their ultimate application.
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49Chen, Y. T.; Kolhatkar, A. G.; Zenasni, O.; Xu, S.; Lee, T. R. Biosensing Using Magnetic Particle Detection Techniques. Sensors 2017, 17, 2300, DOI: 10.3390/s1710230049https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXkt1Cns78%253D&md5=419ac0252c46f6e9e64b1dcdf00717c5Biosensing using magnetic particle detection techniquesChen, Yi-Ting; Kolhatkar, Arati G.; Zenasni, Oussama; Xu, Shoujun; Lee, T. RandallSensors (2017), 17 (10), 2300/1-2300/36CODEN: SENSC9; ISSN:1424-8220. (MDPI AG)Magnetic particles are widely used as signal labels in a variety of biol. sensing applications, such as mol. detection and related strategies that rely on ligand-receptor binding. In this review, we explore the fundamental concepts involved in designing magnetic particles for biosensing applications and the techniques used to detect them. First, we briefly describe the magnetic properties that are important for bio-sensing applications and highlight the assocd. key parameters (such as the starting materials, size, functionalization methods, and bio-conjugation strategies). Subsequently, we focus on magnetic sensing applications that utilize several types of magnetic detection techniques: spintronic sensors, NMR (NMR) sensors, superconducting quantum interference devices (SQUIDs), sensors based on the at. magnetometer (AM), and others. From the studies reported, we note that the size of the MPs is one of the most important factors in choosing a sensing technique.
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50Rocha-Santos, T. A. P. Sensors and Biosensors Based on Magnetic Nanoparticles. TrAC, Trends Anal. Chem. 2014, 62, 28– 36, DOI: 10.1016/j.trac.2014.06.01650https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsVWqs7zO&md5=4e017d8a8f1dd35543423e40cb49b306Sensors and biosensors based on magnetic nanoparticlesRocha-Santos, Teresa A. P.TrAC, Trends in Analytical Chemistry (2014), 62 (), 28-36CODEN: TTAEDJ; ISSN:0165-9936. (Elsevier B. V.)Magnetic nanoparticles (MNPs) have attracted a growing interest in the development and fabrication of sensors and biosensors for several applications. MNPs can be integrated into the transducer materials and/or be dispersed in the sample followed by their attraction by an external magnetic field onto the active detection surface of the (bio)sensor. This review describes and discusses the recent applications of MNPs in sensors and biosensors, taking into consideration their anal. figures of merit. This work also addresses the future trends and perspectives of sensors and biosensors based on MNPs.
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51Lee, A. H. F.; Gessert, S. F.; Chen, Y.; Sergeev, N. V.; Haghiri, B. Preparation of Iron Oxide Silica Particles for Zika Viral RNA Extraction. Heliyon 2018, 4, e00572, DOI: 10.1016/j.heliyon.2018.e00572There is no corresponding record for this reference.
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52Wang, J.; Ali, Z.; Si, J.; Wang, N.; He, N.; Li, Z. Simultaneous Extraction of DNA and RNA from Hepatocellular Carcinoma (Hep G2) Based on Silica-Coated Magnetic Nanoparticles. J. Nanosci. Nanotechnol. 2017, 17, 802– 806, DOI: 10.1166/jnn.2017.1244252https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtVCntLrN&md5=29144f4703bd9195d147b23a1fdd252aSimultaneous extraction of DNA and RNA from hepatocellular carcinoma (Hep G2) based on silica-coated magnetic nanoparticlesWang, Jiuhai; Ali, Zeeshan; Si, Jin; Wang, Nianyue; He, Nongyue; Li, ZhiyangJournal of Nanoscience and Nanotechnology (2017), 17 (1), 802-806CODEN: JNNOAR; ISSN:1533-4880. (American Scientific Publishers)Nucleic acid (NA) extn. from cancer cells is an essential step in mol. oncol. testing. The conventional NA extn. protocols, based on several ultracentrifugation steps, suffer from time-consuming and complex manipulation. Here, a magnetic nanoparticle (MNP) based method for simultaneous extn. of DNA and RNA from cancer cells is described. This MNP based technique has received great attention and significant interest due to its convenient manipulation, low cost and ease for automation. Different factors including lysis buffer, ethanol, MNPs and washing buffers which may affect the yield of nucleic acid were optimized. The av. yield of DNA and RNA obtained from 1 mL Hep G2 (∼106 cells) ranged from 9.7 to 14.7 μg with A260/A280 values between 1.68 and 2.01. The isolated DNA and RNA, using this method, were suitable for downstream activities such as PCR and RT-PCR.
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53Zhang, H.; Xu, T.; Li, C.-W.; Yang, M. A Microfluidic Device with Microbead Array for Sensitive Virus Detection and Genotyping Using Quantum Dots as Fluorescence Labels. Biosens. Bioelectron. 2010, 25, 2402– 2407, DOI: 10.1016/j.bios.2010.02.03253https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXmslOjs7w%253D&md5=33d47aea793823a8ddc38db264ef8e50A microfluidic device with microbead array for sensitive virus detection and genotyping using quantum dots as fluorescence labelsZhang, He; Xu, Tao; Li, Cheuk-Wing; Yang, MengsuBiosensors & Bioelectronics (2010), 25 (11), 2402-2407CODEN: BBIOE4; ISSN:0956-5663. (Elsevier B.V.)In this study, a novel microfluidic device with microbead array was developed and sensitive genotyping of HBV was demonstrated using quantum dot as labels. This device was assembled by using two PDMS slabs featured with different microstructures and channel depths for the construction of a functional region comprising a chamber array and a single sampling microchannel. Since the chamber array and its sampling channel are of different channel depths and are bonded face-to-face, weir structures are generated to confine the microbeads which could be addressed using the microfluidic channel. Highly sensitive virus DNA detection was achieved by the enhanced mass transport in the microfluidics and the rapid reaction dynamics of suspension microbead array. The device could detect 1000 copies/mL of HBV virus in clin. serum samples using in vitro transcribed RNA as the target mols. Based on DNA hybridization with quantum dots labels, on-chip virus genotyping was also demonstrated with high discrimination specificity and sensitivity (4 pM, S/N >3) using synthesized HBV DNA probes. This microfluidic device combines the rapid binding kinetics of homogeneous assays of microbead array, the liq. handling capability of microfluidics, and the fluorescence detection sensitivity of quantum dots to provide a platform for high sensitivity virus DNA anal. with small reagent consumption, short assay time and parallel detection.
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54Wang, T.; Zheng, Z.; Zhang, X.-E.; Wang, H. Quantum Dot-Fluorescence In Situ Hybridisation for Ectromelia Virus Detection Based on Biotin–Streptavidin Interactions. Talanta 2016, 158, 179– 184, DOI: 10.1016/j.talanta.2016.04.05254https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XoslyktLg%253D&md5=7ead7412aa12e47ba598cb9c2be1e4e5Quantum dot-fluorescence in situ hybridization for Ectromelia virus detection based on biotin-streptavidin interactionsWang, Ting; Zheng, Zhenhua; Zhang, Xian-En; Wang, HanzhongTalanta (2016), 158 (), 179-184CODEN: TLNTA2; ISSN:0039-9140. (Elsevier B.V.)Ectromelia virus (ECTV) is an pathogen that can lead to a lethal, acute toxic disease known as mouse-pox in mice. Prevention and control of ECTV infection requires the establishment of a rapid and sensitive diagnostic system for detecting the virus. In the present study, we developed a method of quantum-dot-fluorescence based in situ hybridization for detecting ECTV genome DNA. Using biotin-dUTP to replace dTTP, biotin was incorporated into a DNA probe during polymerase chain reaction. High sensitivity and specificity of ECTV DNA detection were displayed by fluorescent quantum dots based on biotin-streptavidin interactions. ECTV DNA was then detected by streptavidin-conjugated quantum dots that bound the biotin-labeled probe. Results indicated that the established method can visualize ECTV genomic DNA in both infected cells and mouse tissues. To our knowledge, this is the first study reporting quantum-dot-fluorescence based in situ hybridization for the detection of viral nucleic acids, providing a ref. for the identification and detection of other viruses.
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55Papp, I.; Sieben, C.; Ludwig, K.; Roskamp, M.; Böttcher, C.; Schlecht, S.; Herrmann, A.; Haag, R. Inhibition of Influenza Virus Infection by Multivalent Sialic-Acid-Functionalized Gold Nanoparticles. Small 2010, 6, 2900– 2906, DOI: 10.1002/smll.20100134955https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhsFGgsL7F&md5=c6aa4a528310d64f87acd885e16c3692Inhibition of Influenza Virus Infection by Multivalent Sialic-Acid-Functionalized Gold NanoparticlesPapp, Ilona; Sieben, Christian; Ludwig, Kai; Roskamp, Meike; Boettcher, Christoph; Schlecht, Sabine; Herrmann, Andreas; Haag, RainerSmall (2010), 6 (24), 2900-2906CODEN: SMALBC; ISSN:1613-6810. (Wiley-VCH Verlag GmbH & Co. KGaA)An efficient synthesis of sialic-acid-terminated glycerol dendron to chem. functionalize 2 nm and 14 nm gold nanoparticles (AuNPs) is described. These nanoparticles are highly stable and show high activity towards the inhibition of influenza virus infection. As the binding of the viral fusion protein hemagglutinin to the host cell surface is mediated by sialic acid receptors, a multivalent interaction with sialic-acid-functionalized AuNPs is expected to competitively inhibit viral infection. Electron microscopy techniques and biochem. anal. show a high binding affinity of the 14 nm AuNPs to hemagglutinin on the virus surface and, less efficiently, to isolated hemagglutinin. The functionalized AuNPs are nontoxic to the cells under the conditions studied. This approach allows a new type of mol.-imaging activity-correlation and is of particular relevance for further application in alternative antiviral therapy.
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56Sametband, M.; Shukla, S.; Meningher, T.; Hirsh, S.; Mendelson, E.; Sarid, R.; Gedanken, A.; Mandelboim, M. Effective Multi-Strain Inhibition of Influenza Virus by Anionic Gold Nanoparticles. MedChemComm 2011, 2, 421– 423, DOI: 10.1039/c0md00229a56https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXls1Khtrk%253D&md5=2caa7a1ef8db801d9e31b76f9927f01aEffective multi-strain inhibition of influenza virus by anionic gold nanoparticlesSametband, Matias; Shukla, Sourabh; Meningher, Tal; Hirsh, Shira; Mendelson, Ella; Sarid, Ronit; Gedanken, Aharon; Mandelboim, MichalMedChemComm (2011), 2 (5), 421-423CODEN: MCCEAY; ISSN:2040-2503. (Royal Society of Chemistry)The fight against highly contagious influenza infection is often hampered by the appearance of drug resistant strains and the inadequacy of vaccines targeted only against specific variants. The authors report a novel route to inhibit influenza using anionic gold nanoparticles, which show effective inhibition properties against several influenza strains. The inhibition of influenza, achieved through gold nanoparticles with different anionic groups, suggested that blocking of viral attachment to cell surface could be the primary mechanism of inhibition, although viral fusion inhibition could not be excluded. At the same time, variation in the degree of inhibition with the anionic groups indicated that the antiviral activity of the nanoparticles is not merely governed by the charge d. but the functional group itself has a role to play.
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57Cagno, V.; Andreozzi, P.; D’Alicarnasso, M.; Jacob Silva, P.; Mueller, M.; Galloux, M.; Le Goffic, R.; Jones, S. T.; Vallino, M.; Hodek, J.; Weber, J.; Sen, S.; Janeček, E.-R.; Bekdemir, A.; Sanavio, B.; Martinelli, C.; Donalisio, M.; Rameix Welti, M.-A.; Eleouet, J.-F.; Han, Y.; Kaiser, L.; Vukovic, L.; Tapparel, C.; Král, P.; Krol, S.; Lembo, D.; Stellacci, F. Broad-Spectrum Non-Toxic Antiviral Nanoparticles with a Virucidal Inhibition Mechanism. Nat. Mater. 2018, 17, 195– 203, DOI: 10.1038/nmat505357https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhvF2lsbzN&md5=d66943a3a85ef5f924e1dd09fc308b59Broad-spectrum non-toxic antiviral nanoparticles with a virucidal inhibition mechanismCagno, Valeria; Andreozzi, Patrizia; D'Alicarnasso, Marco; Silva, Paulo Jacob; Mueller, Marie; Galloux, Marie; Le Goffic, Ronan; Jones, Samuel T.; Vallino, Marta; Hodek, Jan; Weber, Jan; Sen, Soumyo; Janecek, Emma-Rose; Bekdemir, Ahmet; Sanavio, Barbara; Martinelli, Chiara; Donalisio, Manuela; Rameix Welti, Marie-Anne; Eleouet, Jean-Francois; Han, Yanxiao; Kaiser, Laurent; Vukovic, Lela; Tapparel, Caroline; Kral, Petr; Krol, Silke; Lembo, David; Stellacci, FrancescoNature Materials (2018), 17 (2), 195-203CODEN: NMAACR; ISSN:1476-1122. (Nature Research)Viral infections kill millions yearly. Available antiviral drugs are virus-specific and active against a limited panel of human pathogens. There are broad-spectrum substances that prevent the first step of virus-cell interaction by mimicking heparan sulfate proteoglycans (HSPG), the highly conserved target of viral attachment ligands (VALs). The reversible binding mechanism prevents their use as a drug, because, upon diln., the inhibition is lost. Known VALs are made of closely packed repeating units, but the aforementioned substances are able to bind only a few of them. We designed antiviral nanoparticles with long and flexible linkers mimicking HSPG, allowing for effective viral assocn. with a binding that we simulate to be strong and multivalent to the VAL repeating units, generating forces (∼190 pN) that eventually lead to irreversible viral deformation. Virucidal assays, electron microscopy images, and mol. dynamics simulations support the proposed mechanism. These particles show no cytotoxicity, and in vitro nanomolar irreversible activity against herpes simplex virus (HSV), human papilloma virus, respiratory syncytial virus (RSV), dengue and lenti virus. They are active ex vivo in human cervicovaginal histocultures infected by HSV-2 and in vivo in mice infected with RSV.
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58Kim, J.; Yeom, M.; Lee, T.; Kim, H.-O.; Na, W.; Kang, A.; Lim, J.-W.; Park, G.; Park, C.; Song, D.; Haam, S. Porous Gold Nanoparticles for Attenuating Infectivity of Influenza a Virus. J. Nanobiotechnol. 2020, 18, 54, DOI: 10.1186/s12951-020-00611-858https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXlvFGhu7c%253D&md5=8ecafadf59d12e990f4090ba2f87820bPorous gold nanoparticles for attenuating infectivity of influenza A virusKim, Jinyoung; Yeom, Minjoo; Lee, Taeksu; Kim, Hyun-Ouk; Na, Woonsung; Kang, Aram; Lim, Jong-Woo; Park, Geunseon; Park, Chaewon; Song, Daesub; Haam, SeungjooJournal of Nanobiotechnology (2020), 18 (1), 54CODEN: JNOAAO; ISSN:1477-3155. (BioMed Central Ltd.)Abstr.: Background: Influenza viruses (IVs) have become increasingly resistant to antiviral drugs that target neuraminidase and matrix protein 2 due to gene mutations that alter their drug-binding target protein regions. Consequently, almost all recent IV pandemics have exhibited resistance to com. antiviral vaccines. To overcome this challenge, an antiviral target is needed that is effective regardless of genetic mutations. Main body: In particular, hemagglutinin (HA), a highly conserved surface protein across many IV strains, could be an effective antiviral target as it mediates binding of IVs with host cell receptors, which is crucial for membrane fusion. HA has 6 disulfide bonds that can easily bind with the surfaces of gold nanoparticles. Herein, we fabricated porous gold nanoparticles (PoGNPs) via a surfactant-free emulsion method that exhibited strong affinity for disulfide bonds due to gold-thiol interactions, and provided extensive surface area for these interactions. A remarkable decrease in viral infectivity was demonstrated by increased cell viability results after exposing MDCK cells to various IV strains (H1N1, H3N2, and H9N2) treated with PoGNP. Most of all, the viability of MDCK cells infected with all IV strains increased to 96.8% after PoGNP treatment of the viruses compared to 33.9% cell viability with non-treated viruses. Intracellular viral RNA quantification by real-time RT-PCR also confirmed that PoGNP successfully inhibited viral membrane fusion by blocking the viral entry process through conformational deformation of HA. Conclusion: We believe that the technique described herein can be further developed for PoGNP-utilized antiviral protection as well as metal nanoparticle-based therapy to treat viral infection. Addnl., facile detection of IAV can be achieved by developing PoGNP as a multiplatform for detection of the virus.
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59Huang, X.; Li, M.; Xu, Y.; Zhang, J.; Meng, X.; An, X.; Sun, L.; Guo, L.; Shan, X.; Ge, J.; Chen, J.; Luo, Y.; Wu, H.; Zhang, Y.; Jiang, Q.; Ning, X. Novel Gold Nanorod-Based HR1 Peptide Inhibitor for Middle East Respiratory Syndrome Coronavirus. ACS Appl. Mater. Interfaces 2019, 11, 19799– 19807, DOI: 10.1021/acsami.9b0424059https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXpvVClsro%253D&md5=59aff1b3a8c12706e2f45245c23f59deNovel Gold Nanorod-Based HR1 Peptide Inhibitor for Middle East Respiratory Syndrome CoronavirusHuang, Xinyu; Li, Meng; Xu, Yurui; Zhang, Jikang; Meng, Xia; An, Xueying; Sun, Lei; Guo, Leilei; Shan, Xue; Ge, Junliang; Chen, Jiao; Luo, Yadong; Wu, Heming; Zhang, Yu; Jiang, Qing; Ning, XinghaiACS Applied Materials & Interfaces (2019), 11 (22), 19799-19807CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Middle East respiratory syndrome coronavirus (MERS-CoV) causes a severe acute respiratory syndrome-like illness with high pathogenicity and mortality due to the lack of effective therapeutics. Currently, only few antiviral agents are available for the treatment of MERS, but their effects have been greatly impaired by low antiviral activity, poor metabolic stability, and serious adverse effects. Therefore, the development of effective treatment for MERS is urgently needed. In this study, a series of heptad repeat 1 (HR1) peptide inhibitors have been developed to inhibit HR1/HR2-mediated membrane fusion between MERS-CoV and host cells, which is the major pathway of MERS-CoV-induced host infections. Particularly, peptide pregnancy-induced hypertension (PIH) exhibits potent inhibitory activity with IC50 of 1.171 μM, and its inhibitory effects can be further increased to 10-fold by forming a gold nanorod complex (PIH-AuNRs). In addn., PIH-AuNRs display enhanced metabolic stability and biocompatibility in vitro and in vivo and, therefore, effectively prevent MERS-CoV-assocd. membrane fusion. In summary, PIH-AuNRs represent a novel class of antiviral agents and have a great potential in treating MERS in the clinic.
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60Yang, X. X.; Li, C. M.; Huang, C. Z. Curcumin Modified Silver Nanoparticles for Highly Efficient Inhibition of Respiratory Syncytial Virus Infection. Nanoscale 2016, 8, 3040– 3048, DOI: 10.1039/C5NR07918G60https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XislKnsw%253D%253D&md5=8a288a70879432df568881c84b1d6046Curcumin modified silver nanoparticles for highly efficient inhibition of respiratory syncytial virus infectionYang, Xiao Xi; Li, Chun Mei; Huang, Cheng ZhiNanoscale (2016), 8 (5), 3040-3048CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)Interactions between nanoparticles and viruses have attracted increasing attention due to the antiviral activity of nanoparticles and the resulting possibility to be employed as biomedical interventions. In this contribution, we developed a very simple route to prep. uniform and stable silver nanoparticles (AgNPs) with antiviral properties by using curcumin, which is a member of the ginger family isolated from rhizomes of the perennial herb Curcuma longa and has a wide range of biol. activities like antioxidant, antifungal, antibacterial and anti-inflammatory effects, and acts as reducing and capping agents in this synthetic route. The tissue culture infectious dose (TCID50) assay showed that the curcumin modified silver nanoparticles (cAgNPs) have a highly efficient inhibition effect against respiratory syncytial virus (RSV) infection, giving a decrease of viral titers about two orders of magnitude at the concn. of cAgNPs under which no toxicity was found to the host cells. Mechanism investigations showed that cAgNPs could prevent RSV from infecting the host cells by inactivating the virus directly, indicating that cAgNPs are a novel promising efficient virucide for RSV.
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61Chen, Y.-N.; Hsueh, Y.-H.; Hsieh, C.- T.; Tzou, D.-Y.; Chang, P.-L. Antiviral Activity of Graphene–Silver Nanocomposites against Non-Enveloped and Enveloped Viruses. Int. J. Environ. Res. Public Health 2016, 13, 430, DOI: 10.3390/ijerph1304043061https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXivVWhs7Y%253D&md5=3a1be06dc09934ca4a8593d834e5bf57Antiviral activity of graphene-silver nanocomposites against non-enveloped and enveloped virusesChen, Yi-Ning; Hsueh, Yi-Huang; Hsieh, Chien-Te; Tzou, Dong-Ying; Chang, Pai-LingInternational Journal of Environmental Research and Public Health (2016), 13 (4), 430/1-430/12CODEN: IJERGQ; ISSN:1660-4601. (MDPI AG)The discovery of novel antiviral materials is important because many infectious diseases are caused by viruses. Silver nanoparticles have demonstrated strong antiviral activity, and graphene is a potential antimicrobial material due to its large surface area, high carrier mobility, and biocompatibility. No studies on the antiviral activity of nanomaterials on non-enveloped viruses have been reported. To investigate the antiviral activity of graphene oxide (GO) sheets and GO sheets with silver particles (GO-Ag) against enveloped and non-enveloped viruses, feline coronavirus (FCoV) with an envelope and infectious bursal disease virus (IBDV) without an envelope were chosen. The morphol. and sizes of GO and GO-Ag were characterized by transmission, SEM, and X-ray diffraction. A virus inhibition assay was used to identify the antiviral activity of GO and GO-Ag. Go-Ag inhibited 25% of infection by FCoV and 23% by IBDV, whereas GO only inhibited 16% of infection by FCoV but showed no antiviral activity against the infection by IBDV. Further application of GO and GO-Ag can be considered for personal protection equipment to decrease the transmission of viruses.
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62Lv, X.; Wang, P.; Bai, R.; Cong, Y.; Suo, S.; Ren, X.; Chen, C. Inhibitory Effect of Silver Nanomaterials on Transmissible Virus-Induced Host Cell Infections. Biomaterials 2014, 35, 4195– 4203, DOI: 10.1016/j.biomaterials.2014.01.05462https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXitFOqt7s%253D&md5=4c8e2c3bc5e136c8cacd397da707e900Inhibitory effect of silver nanomaterials on transmissible virus-induced host cell infectionsLv, Xiaonan; Wang, Peng; Bai, Ru; Cong, Yingying; Suo, Siqingaowa; Ren, Xiaofeng; Chen, ChunyingBiomaterials (2014), 35 (13), 4195-4203CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)Coronaviruses belong to the family Coronaviridae, which primarily cause infection of the upper respiratory and gastrointestinal tract of hosts. Transmissible gastroenteritis virus (TGEV) is an economically significant coronavirus that can cause severe diarrhea in pigs. Silver nanomaterials (Ag NMs) have attracted great interests in recent years due to their excellent anti-microorganism properties. Herein, four representative Ag NMs including spherical Ag nanoparticles (Ag NPs, NM-300), two kinds of silver nanowires (XFJ011) and silver colloids (XFJ04) were selected to study their inhibitory effect on TGEV-induced host cell infection in vitro. Ag NPs were uniformly distributed, with particle sizes less than 20 nm by characterization of environmental scanning electron microscope and transmission electron microscope. Two types of silver nanowires were 60 nm and 400 nm in diam., resp. The av. diam. of the silver colloids was approx. 10 nm. TGEV infection induced the occurring of apoptosis in swine testicle (ST) cells, down-regulated the expression of Bcl-2, up-regulated the expression of Bax, altered mitochondrial membrane potential, activated p38 MAPK signal pathway, and increased expression of p53 as evidenced by immunofluorescence assays, real-time PCR, flow cytometry and Western blot. Under non-toxic concns., Ag NPs and silver nanowires significantly diminished the infectivity of TGEV in ST cells. Moreover, further results showed that Ag NPs and silver nanowires decreased the no. of apoptotic cells induced by TGEV through regulating p38/mitochondria-caspase-3 signaling pathway. Our data indicate that Ag NMs are effective in prevention of TGEV-mediated cell infection as a virucidal agent or as an inhibitor of viral entry and the present findings may provide new insights into antiviral therapy of coronaviruses.
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63Li, Y.; Lin, Z.; Zhao, M.; Xu, T.; Wang, C.; Hua, L.; Wang, H.; Xia, H.; Zhu, B. Silver Nanoparticle Based Codelivery of Oseltamivir to Inhibit the Activity of the H1N1 Influenza Virus through ROS-Mediated Signaling Pathways. ACS Appl. Mater. Interfaces 2016, 8, 24385– 24393, DOI: 10.1021/acsami.6b0661363https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhsVCmsb7O&md5=83513b12fe12d52dcf72a9129e8f9dc0Silver Nanoparticle Based Codelivery of Oseltamivir to Inhibit the Activity of the H1N1 Influenza Virus through ROS-Mediated Signaling PathwaysLi, Yinghua; Lin, Zhengfang; Zhao, Mingqi; Xu, Tiantian; Wang, Changbing; Hua, Liang; Wang, Hanzhong; Xia, Huimin; Zhu, BingACS Applied Materials & Interfaces (2016), 8 (37), 24385-24393CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)As the therapeutic agent for antiviral applications, the clin. use of oseltamivir is limited with the appearance of drug-resistant viruses. It is important to explore novel anti-influenza drugs. The antiviral activity of silver nanoparticles (AgNPs) has attracted increasing attention in recent years and was a possibility to be employed as a biomedical intervention. Herein, we describe the synthesis of surface decoration of AgNPs by using oseltamivir (OTV) with antiviral properties and inhibition of drug resistance. Compared to silver and oseltamivir, oseltamivir-modified AgNPs (Ag@OTV) have remarkable inhibition against H1N1 infection, and less toxicity was found for MDCK cells by controlled-potential electrolysis (CPE), MTT, and transmission electron microscopy (TEM). Furthermore, Ag@OTV inhibited the activity of neuraminidase (NA) and hemagglutinin (HA) and then prevented the attachment of the H1N1 influenza virus to host cells. The investigations of the mechanism revealed that Ag@OTV could block H1N1 from infecting MDCK cells and prevent DNA fragmentation, chromatin condensation, and the activity of caspase-3. Ag@OTV remarkably inhibited the accumulation of reactive oxygen species (ROS) by the H1N1 virus and activation of AKT and p53 phosphorylation. Silver nanoparticle based codelivery of oseltamivir inhibits the activity of the H1N1 influenza virus through ROS-mediated signaling pathways. These findings demonstrate that Ag@OTV is a novel promising efficient virucide for H1N1.
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64Lin, Z.; Li, Y.; Guo, M.; Xu, T.; Wang, C.; Zhao, M.; Wang, H.; Chen, T.; Zhu, B. The Inhibition of H1N1 Influenza Virus-Induced Apoptosis by Silver Nanoparticles Functionalized with Zanamivir. RSC Adv. 2017, 7, 742– 750, DOI: 10.1039/C6RA25010F64https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtFGqtQ%253D%253D&md5=ebe5676ff40cc5fd2b1affb532bc0461The inhibition of H1N1 influenza virus-induced apoptosis by silver nanoparticles functionalized with zanamivirLin, Zhengfang; Li, Yinghua; Guo, Min; Xu, Tiantian; Wang, Changbing; Zhao, Mingqi; Wang, Hanzhong; Chen, Tianfeng; Zhu, BingRSC Advances (2017), 7 (2), 742-750CODEN: RSCACL; ISSN:2046-2069. (Royal Society of Chemistry)As one of the most effective drugs for influenza virus infection, clin. application of zanamivir is restricted with the emergence of resistant influenza virus. It is crucial to manuf. novel pharmaceuticals against influenza virus infection. In recent years silver nanoparticles (AgNPs) have attracted wide attention in the antiviral field. In this study, we demonstrated surface decoration of AgNPs using zanamivir (ZNV) with antiviral properties. AgNPs co-delivery of the zanamivir nanosystem was designed to reverse influenza virus resistance. In brief, zanamivir modified AgNPs (Ag@ZNV) inhibited the neuraminidase activity of the H1N1 virus. Moreover, cytopathic effect showed that Ag@ZNV remarkably resisted H1N1 virus-induced apoptosis of MDCK cells, involving DNA fragmentation, chromatin condensation and caspase-3 activation. Ag@ZNV effectively reduced the accumulation of reactive oxygen species (ROS) induced by H1N1 virus and activation of both p38 and p53 signaling pathways. Taken together, our study indicates that Ag@ZNV is a novel promising pharmaceutical against H1N1 influenza virus infection.
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65Morris, D.; Ansar, M.; Speshock, J.; Ivanciuc, T.; Qu, Y.; Casola, A.; Garofalo, R. Antiviral and Immunomodulatory Activity of Silver Nanoparticles in Experimental RSV Infection. Viruses 2019, 11, 732, DOI: 10.3390/v1108073265https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXisVOgu7bO&md5=a86c312d757577abef2166f0ec25d98eAntiviral and immunomodulatory activity of silver nanoparticles in experimental RSV infectionMorris, Dorothea; Ansar, Maria; Speshock, Janice; Ivanciuc, Teodora; Qu, Yue; Casola, Antonella; Garofalo, Roberto P.Viruses (2019), 11 (8), 732CODEN: VIRUBR; ISSN:1999-4915. (MDPI AG)Wild birds play an important role as reservoir hosts and vectors for zoonotic arboviruses and foster their spread. Usutu virus (USUV) has been circulating endemically in Germany since 2011, while West Nile virus (WNV) was first diagnosed in several bird species and horses in 2018. In 2017 and 2018, we screened 1709 live wild and zoo birds with real-time polymerase chain reaction and serol. assays. Moreover, organ samples from bird carcasses submitted in 2017 were investigated. Overall, 57 blood samples of the live birds (2017 and 2018), and 100 organ samples of dead birds (2017) were pos. for USUV-RNA, while no WNV-RNA-pos. sample was found. Phylogenetic anal. revealed the first detection of USUV lineage Europe 2 in Germany and the spread of USUV lineages Europe 3 and Africa 3 towards Northern Germany. USUV antibody prevalence rates were high in Eastern Germany in both years. On the contrary, in Northern Germany, high seroprevalence rates were first detected in 2018, with the first emergence of USUV in this region. Interestingly, high WNV-specific neutralizing antibody titers were obsd. in resident and short-distance migratory birds in Eastern Germany in 2018, indicating the first signs of a local WNV circulation.
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66Osminkina, L. A.; Timoshenko, V. Y.; Shilovsky, I. P.; Kornilaeva, G. V.; Shevchenko, S. N.; Gongalsky, M. B.; Tamarov, K. P.; Abramchuk, S. S.; Nikiforov, V. N.; Khaitov, M. R.; Karamov, E. V. Porous Silicon Nanoparticles as Scavengers of Hazardous Viruses. J. Nanopart. Res. 2014, 16, 2430, DOI: 10.1007/s11051-014-2430-2There is no corresponding record for this reference.
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67Lin, Z.; Li, Y.; Guo, M.; Xiao, M.; Wang, C.; Zhao, M.; Xu, T.; Xia, Y.; Zhu, B. Inhibition of H1N1 Influenza Virus by Selenium Nanoparticles Loaded with Zanamivir through P38 and Jnk Signaling Pathways. RSC Adv. 2017, 7, 35290– 35296, DOI: 10.1039/C7RA06477B67https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtFOlsLfL&md5=00f058686a48fa9dcc1271b7f477cfb7Inhibition of H1N1 influenza virus by selenium nanoparticles loaded with zanamivir through p38 and JNK signaling pathwaysLin, Zhengfang; Li, Yinghua; Guo, Min; Xiao, Misi; Wang, Changbing; Zhao, Mingqi; Xu, Tiantian; Xia, Yu; Zhu, BingRSC Advances (2017), 7 (56), 35290-35296CODEN: RSCACL; ISSN:2046-2069. (Royal Society of Chemistry)Zanamivir is an effective drug for influenza virus infection, but strong mol. polarity and aq. soly. limit its clin. application. In recent years, selenium nanoparticles (SeNPs) have attracted attention in the biol. field. In this study, surface decoration of SeNPs using zanamivir (ZNV) with antiviral properties was demonstrated. SeNPs co-delivery of a zanamivir nanosystem was designed to reverse influenza virus infection. In breif, the MTT assay, cytopathic effect and nucleic acid level of the virus suggested that zanamivir modified SeNPs (Se@ZNV) resisted proliferation of H1N1 virus and MDCK cells achieved higher viability after treatment with this compd. Besides, both activation and expression of caspase-3 induced during H1N1 virus infection were depressed when treated with Se@ZNV. Furthermore, phosphorylation of p38 and JNK were down-regulated by Se@ZNV. Taken together, our study indicates that Se@ZNV is a novel promising pharmaceutical against H1N1 influenza virus infection.
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68Li, Y.; Lin, Z.; Guo, M.; Zhao, M.; Xia, Y.; Wang, C.; Xu, T.; Zhu, B. Inhibition of H1N1 Influenza Virus-Induced Apoptosis by Functionalized Selenium Nanoparticles with Amantadine through ROS-Mediated AKT Signaling Pathways. Int. J. Nanomed. 2018, 13, 2005– 2016, DOI: 10.2147/IJN.S15599468https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXit1GltbrK&md5=43468dbd3ff9129de5293748586e6a67Inhibition of H1N1 influenza virus-induced apoptosis by functionalized selenium nanoparticles with amantadine through ROS-mediated AKT signaling pathwaysLi, Yinghua; Lin, Zhengfang; Guo, Min; Zhao, Mingqi; Xia, Yu; Wang, Changbing; Xu, TiantianInternational Journal of Nanomedicine (2018), 13 (), 2005-2016CODEN: IJNNHQ; ISSN:1178-2013. (Dove Medical Press Ltd.)Introduction: As a therapeutic antiviral agent, the clin. application of amantadine (AM) is limited by the emergence of drug-resistant viruses. To overcome the drug-resistant viruses and meet the growing demand of clin. diagnosis, the use of biol. nanoparticles (NPs) has increased in order to develop novel anti-influenza drugs. The antiviral activity of selenium NPs with low toxicity and excellent activities has attracted increasing attention for biomedical intervention in recent years. Methods and results: In the present study, surface decoration of selenium NPs by AM (Se@AM) was designed to reverse drug resistance caused by influenza virus infection. Se@AM with less toxicity remarkably inhibited the ability of H1N1 influenza to infect host cells through suppression of the neuraminidase activity. Moreover, Se@AM could prevent H1N1 from infecting Madin Darby Canine Kidney cell line and causing cell apoptosis supported by DNA fragmentation and chromatin condensation. Furthermore, Se@AM obviously inhibited the generation of reactive oxygen species and activation of phosphorylation of AKT. Conclusion: These results demonstrate that Se@AM is a potentially efficient antiviral pharmaceutical agent for H1N1 influenza virus.
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69Lin, Z.; Li, Y.; Gong, G.; Xia, Y.; Wang, C.; Chen, Y.; Hua, L.; Zhong, J.; Tang, Y.; Liu, X.; Zhu, B. Restriction of H1N1 Influenza Virus Infection by Selenium Nanoparticles Loaded with Ribavirin Via Resisting Caspase-3 Apoptotic Pathway. Int. J. Nanomed. 2018, 13, 5787– 5797, DOI: 10.2147/IJN.S17765869https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtVems73E&md5=9ab999fccdfe182db4118c262583b0a4Restriction of H1N1 influenza virus infection by selenium nanoparticles loaded with ribavirin via resisting caspase-3 apoptotic pathwayLin, Zhengfang; Li, Yinghua; Gong, Guifang; Xia, Yu; Wang, Changbing; Chen, Yi; Hua, Liang; Zhong, Jiayu; Tang, Ying; Liu, Xiaomin; Zhu, BingInternational Journal of Nanomedicine (2018), 13 (), 5787-5797CODEN: IJNNHQ; ISSN:1178-2013. (Dove Medical Press Ltd.)Ribavirin (RBV) is a broad-spectrum antiviral drug. Selenium nanoparticles (SeNPs) attract much attention in the biomedical field and are used as carriers of drugs in current research studies. In this study, SeNPs were decorated by RBV, and the novel nanoparticle system was well characterized. Madin-Darby Canine Kidney cells were infected with H1N1 influenza virus before treatment with RBV, SeNPs, and SeNPs loaded with RBV (Se@RBV). MTT assay showed that Se@RBV nanoparticles protect cells during H1N1 infection in vitro. Se@RBV depressed virus titer in the culture supernatant. Intracellular localization detection revealed that Se@RBV accumulated in lysosome and escaped to cytoplasm as time elapsed. Furthermore, activation of caspase-3 was resisted by Se@RBV. Expressions of proteins related to caspase-3, including cleaved poly-ADP-ribose polymerase, caspase-8, and Bax, were downregulated evidently after treatment with Se@RBV compared with the untreated infection group. In addn., phosphorylations of phosphorylated 38 (p38), JNK, and phosphorylated 53 (p53) were inhibited as well. In vivo expts. indicated that Se@RBV was found to prevent lung injury in H1N1-infected mice through hematoxylin and eosin staining. Tunel test of lung tissues present that DNA damage reached a high level but reduced substantially when treated with Se@RBV. Immunohistochem. test revealed an identical result with the in vitro expt. that activations of caspase-3 and proteins on the apoptosis pathway were restrained by Se@RBV treatment. Taken together, this study elaborates that Se@RBV is a novel promising agent against H1N1 influenza virus infection.
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70Li, Y.; Lin, Z.; Guo, M.; Xia, Y.; Zhao, M.; Wang, C.; Xu, T.; Chen, T.; Zhu, B. Inhibitory Activity of Selenium Nanoparticles Functionalized with Oseltamivir on H1N1 Influenza Virus. Int. J. Nanomed. 2017, 12, 5733– 5743, DOI: 10.2147/IJN.S14093970https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXitV2gtrzL&md5=cf69da91ddf57bcaedcf1139179f7f54Inhibitory activity of selenium nanoparticles functionalized with oseltamivir on H1N1 influenza virusLi, Yinghua; Lin, Zhengfang; Guo, Min; Xia, Yu; Zhao, Mingqi; Wang, Changbing; Xu, Tiantian; Chen, Tianfeng; Zhu, BingInternational Journal of Nanomedicine (2017), 12 (), 5733-5743CODEN: IJNNHQ; ISSN:1178-2013. (Dove Medical Press Ltd.)As an effective antiviral agent, the clin. application of oseltamivir (OTV) is limited by the appearance of drug-resistant viruses. Due to their low toxicity and excellent activity, the antiviral capabilities of selenium nanoparticles (SeNPs) has attracted increasing attention in recent years. To overcome the limitation of drug resistance, the use of modified NPs with biologics to explore novel anti-influenza drugs is developing rapidly. In this study, OTV surface-modified SeNPs with superior antiviral properties and restriction on drug resistance were synthesized. OTV decoration of SeNPs (Se@OTV) obviously inhibited H1N1 infection and had less toxicity. Se@OTV interfered with the H1N1 influenza virus to host cells through inhibiting the activity of hemagglutinin and neuraminidase. The mechanism was that Se@OTV was able to prevent H1N1 from infecting MDCK cells and block chromatin condensation and DNA fragmentation. Furthermore, Se@OTV inhibited the generation of reactive oxygen species and activation of p53 phosphorylation and Akt. These results demonstrate that Se@OTV is a promising efficient antiviral pharmaceutical for H1N1.
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71Ghaffari, H.; Tavakoli, A.; Moradi, A.; Tabarraei, A.; Bokharaei-Salim, F.; Zahmatkeshan, M.; Farahmand, M.; Javanmard, D.; Kiani, S. J.; Esghaei, M.; Pirhajati-Mahabadi, V.; Monavari, S. H.; Ataei-Pirkooh, A. Inhibition of H1N1 Influenza Virus Infection by Zinc Oxide Nanoparticles: Another Emerging Application of Nanomedicine. J. Biomed. Sci. 2019, 26, 70, DOI: 10.1186/s12929-019-0563-471https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3Mrmslemsg%253D%253D&md5=84b81c1eb7a85ec581774b9c524767f1Inhibition of H1N1 influenza virus infection by zinc oxide nanoparticles: another emerging application of nanomedicineGhaffari Hadi; Tavakoli Ahmad; Bokharaei-Salim Farah; Javanmard Davod; Kiani Seyed Jalal; Esghaei Maryam; Monavari Seyed Hamidreza; Ataei-Pirkooh Angila; Moradi Abdolvahab; Tabarraei Alijan; Zahmatkeshan Masoumeh; Pirhajati-Mahabadi Vahid; Zahmatkeshan Masoumeh; Farahmand Mohammad; Pirhajati-Mahabadi VahidJournal of biomedical science (2019), 26 (1), 70 ISSN:.BACKGROUND: Currently available anti-influenza drugs are often associated with limitations such as toxicity and the appearance of drug-resistant strains. Therefore, there is a pressing need for the development of novel, safe and more efficient antiviral agents. In this study, we evaluated the antiviral activity of zinc oxide nanoparticles (ZnO-NPs) and PEGylated zinc oxide nanoparticles against H1N1 influenza virus. METHODS: The nanoparticles were characterized using the inductively coupled plasma mass spectrometry, x-ray diffraction analysis, and electron microscopy. MTT assay was applied to assess the cytotoxicity of the nanoparticles, and anti-influenza activity was determined by TCID50 and quantitative Real-Time PCR assays. To study the inhibitory impact of nanoparticles on the expression of viral antigens, an indirect immunofluorescence assay was also performed. RESULTS: Post-exposure of influenza virus with PEGylated ZnO-NPs and bare ZnO-NPs at the highest non-toxic concentrations could be led to 2.8 and 1.2 log10 TCID50 reduction in virus titer when compared to the virus control, respectively (P < 0.0001). At the highest non-toxic concentrations, the PEGylated and unPEGylated ZnO-NPs led to inhibition rates of 94.6 and 52.2%, respectively, which were calculated based on the viral loads. There was a substantial decrease in fluorescence emission intensity in viral-infected cell treated with PEGylated ZnO-NPs compared to the positive control. CONCLUSIONS: Taken together, our study indicated that PEGylated ZnO-NPs could be a novel, effective, and promising antiviral agent against H1N1 influenza virus infection, and future studies can be designed to explore the exact antiviral mechanism of these nanoparticles.
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72De Souza e Silva, J. M.; Hanchuk, T. D. M.; Santos, M. I.; Kobarg, J.; Bajgelman, M. C.; Cardoso, M. B. Viral Inhibition Mechanism Mediated by Surface-Modified Silica Nanoparticles. ACS Appl. Mater. Interfaces 2016, 8, 16564– 16572, DOI: 10.1021/acsami.6b0334272https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2s%252FosFKgtA%253D%253D&md5=86f7653675a75531f2f1445363822261Viral Inhibition Mechanism Mediated by Surface-Modified Silica Nanoparticlesde Souza E Silva Juliana Martins; Santos Murilo Izidoro; Cardoso Mateus Borba; de Souza E Silva Juliana Martins; Hanchuk Talita Diniz Melo; Kobarg Jorg; Bajgelman Marcio Chaim; Hanchuk Talita Diniz Melo; Kobarg JorgACS applied materials & interfaces (2016), 8 (26), 16564-72 ISSN:.Vaccines and therapies are not available for several diseases caused by viruses, thus viral infections result in morbidity and mortality of millions of people every year. Nanoparticles are considered to be potentially effective in inhibiting viral infections. However, critical issues related to their use include their toxicity and their mechanisms of antiviral action, which are not yet completely elucidated. To tackle these problems, we synthesized silica nanoparticles with distinct surface properties and evaluated their biocompatibility and antiviral efficacy. We show that nanoparticles exhibited no significant toxicity to mammalian cells, while declines up to 50% in the viral transduction ability of two distinct recombinant viruses were observed. We designed experiments to address the mechanism of antiviral action of our nanoparticles and found that their hydrophobic/hydrophilic characters play a crucial role. Our results reveal that the use of functionalized silica particles is a promising approach for controlling viral infection and offer promising strategies for viral control.
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73Bromberg, L.; Bromberg, D. J.; Hatton, T. A.; Bandín, I.; Concheiro, A.; Alvarez-Lorenzo, C. Antiviral Properties of Polymeric Aziridine- and Biguanide-Modified Core–Shell Magnetic Nanoparticles. Langmuir 2012, 28, 4548– 4558, DOI: 10.1021/la205127x73https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhvFahu7g%253D&md5=92c1bdcfdf990cb72de6860dbf4b6cbcAntiviral Properties of Polymeric Aziridine- and Biguanide-Modified Core-Shell Magnetic NanoparticlesBromberg, Lev; Bromberg, Daniel J.; Hatton, T. Alan; Bandin, Isabel; Concheiro, Angel; Alvarez-Lorenzo, CarmenLangmuir (2012), 28 (9), 4548-4558CODEN: LANGD5; ISSN:0743-7463. (American Chemical Society)Polycationic superparamagnetic nanoparticles (∼150-250 nm) were evaluated as virucidal agents. The particles possess a core-shell structure, with cores consisting of magnetite clusters and shells of functional silica covalently bound to poly(hexamethylene biguanide) (PHMBG), polyethyleneimine (PEI), or PEI terminated with aziridine moieties. Aziridine was conjugated to the PEI shell through cationic ring-opening polymn. The nanometric core-shell particles functionalized with biguanide or aziridine moieties are able to bind and inactivate bacteriophage MS2, herpes simplex virus HSV-1, nonenveloped infectious pancreatic necrosis virus (IPNV), and enveloped viral hemorrhagic septicemia virus (VHSV). The virus-particle complexes can be efficiently removed from the aq. milieu by simple magnetocollection.
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74Du, T.; Liang, J.; Dong, N.; Lu, J.; Fu, Y.; Fang, L.; Xiao, S.; Han, H. Glutathione-Capped Ag2S Nanoclusters Inhibit Coronavirus Proliferation through Blockage of Viral RNA Synthesis and Budding. ACS Appl. Mater. Interfaces 2018, 10, 4369– 4378, DOI: 10.1021/acsami.7b1381174https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhtVaqsr0%253D&md5=b1f91d4da40a3d3dcd74cf16d47d9bb1Glutathione-Capped Ag2S Nanoclusters Inhibit Coronavirus Proliferation through Blockage of Viral RNA Synthesis and BuddingDu, Ting; Liang, Jiangong; Dong, Nan; Lu, Jian; Fu, Yiying; Fang, Liurong; Xiao, Shaobo; Han, HeyouACS Applied Materials & Interfaces (2018), 10 (5), 4369-4378CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Development of novel antiviral reagents is of great importance for the control of virus spread. Here, Ag2S nanoclusters (NCs) were proved for the first time to possess highly efficient antiviral activity by using porcine epidemic diarrhea virus (PEDV) as a model of coronavirus. Analyses of virus titers showed that Ag2S NCs significantly suppressed the infection of PEDV by about 3 orders of magnitude at the noncytotoxic concn. at 12 h postinfection, which was further confirmed by the expression of viral proteins. Mechanism investigations indicated that Ag2S NCs treatment inhibits the synthesis of viral neg.-strand RNA and viral budding. Ag2S NCs treatment was also found to pos. regulate the generation of IFN-stimulating genes (ISGs) and the expression of proinflammation cytokines, which might prevent PEDV infection. This study suggest the novel underlying of Ag2S NCs as a promising therapeutic drug for coronavirus.
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75Łoczechin, A.; Séron, K.; Barras, A.; Giovanelli, E.; Belouzard, S.; Chen, Y.-T.; Metzler-Nolte, N.; Boukherroub, R.; Dubuisson, J.; Szunerits, S. Functional Carbon Quantum Dots as Medical Countermeasures to Human Coronavirus. ACS Appl. Mater. Interfaces 2019, 11, 42964– 42974, DOI: 10.1021/acsami.9b1503275https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhvF2ktbvL&md5=fd3d64b54ff8f279bf87bb928983e07eFunctional Carbon Quantum Dots as Medical Countermeasures to Human CoronavirusLoczechin, Aleksandra; Seron, Karin; Barras, Alexandre; Giovanelli, Emerson; Belouzard, Sandrine; Chen, Yen-Ting; Metzler-Nolte, Nils; Boukherroub, Rabah; Dubuisson, Jean; Szunerits, SabineACS Applied Materials & Interfaces (2019), 11 (46), 42964-42974CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Therapeutic options for the highly pathogenic human coronavirus (HCoV) infections are urgently needed. Anti-coronavirus therapy is however challenging, as coronaviruses are biol. diverse and rapidly mutating. The antiviral activity of seven different carbon quantum dots (CQDs) for the treatment of human coronavirus HCoV-229E infections was studied. The first generation of antiviral CQDs was derived by hydrothermal carbonization from ethylenediamine/citric acid as carbon precursors and post-modified with boronic acid ligands. These nanostructures showed a concn. dependent virus inactivation with an estd. EC50 of 52 ± 8μg mL-1. CQDs derived from 4-aminophenylboronic acid without any further modification resulted in the second-generation of anti-HCoV nanomaterials with an EC50 lowered to 5.2 ± 0.7μg mL-1. The underlying mechanism of action of these CQDs revealed to be inhibition of HCoV-229E entry that could be due to interaction of the functional groups of the CQDs with HCoV-229E entry receptors; surprisingly, an equally large inhibition activity was obsd. at the viral replication step.
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76Ting, D.; Dong, N.; Fang, L.; Lu, J.; Bi, J.; Xiao, S.; Han, H. Multisite Inhibitors for Enteric Coronavirus: Antiviral Cationic Carbon Dots Based on Curcumin. ACS Appl. Nano Mater. 2018, 1, 5451– 5459, DOI: 10.1021/acsanm.8b00779There is no corresponding record for this reference.
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77Tong, T.; Hu, H.; Zhou, J.; Deng, S.; Zhang, X.; Tang, W.; Fang, L.; Xiao, S.; Liang, J. Glycyrrhizic-Acid-Based Carbon Dots with High Antiviral Activity by Multisite Inhibition Mechanisms. Small 2020, 16, 1906206, DOI: 10.1002/smll.20190620677https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXjt12rsLY%253D&md5=9dedd5a9f24d0af04d2fecc19d07deb1Glycyrrhizic-Acid-Based Carbon Dots with High Antiviral Activity by Multisite Inhibition MechanismsTong, Ting; Hu, Hongwei; Zhou, Junwei; Deng, Shuangfei; Zhang, Xiaotong; Tang, Wantao; Fang, Liurong; Xiao, Shaobo; Liang, JiangongSmall (2020), 16 (13), 1906206CODEN: SMALBC; ISSN:1613-6810. (Wiley-VCH Verlag GmbH & Co. KGaA)With the gradual usage of carbon dots (CDs) in the area of antiviral research, attempts have been stepped up to develop new antiviral CDs with high biocompatibility and antiviral effects. In this study, a kind of highly biocompatible CDs (Gly-CDs) is synthesized from active ingredient (glycyrrhizic acid) of Chinese herbal medicine by a hydrothermal method. Using the porcine reproductive and respiratory syndrome virus (PRRSV) as a model, it is found that the Gly-CDs inhibit PRRSV proliferation by up to 5 orders of viral titers. Detailed investigations reveal that Gly-CDs can inhibit PRRSV invasion and replication, stimulate antiviral innate immune responses, and inhibit the accumulation of intracellular reactive oxygen species (ROS) caused by PRRSV infection. Proteomics anal. demonstrates that Gly-CDs can stimulate cells to regulate the expression of some host restriction factors, including DDX53 and NOS3, which are directly related to PRRSV proliferation. Moreover, it is found that Gly-CDs also remarkably suppress the propagation of other viruses, such as pseudorabies virus (PRV) and porcine epidemic diarrhea virus (PEDV), suggesting the broad antiviral activity of Gly-CDs. The integrated results demonstrate that Gly-CDs possess extraordinary antiviral activity with multisite inhibition mechanisms, providing a promising candidate for alternative therapy for PRRSV infection.
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78Huang, S.; Gu, J.; Ye, J.; Fang, B.; Wan, S.; Wang, C.; Ashraf, U.; Li, Q.; Wang, X.; Shao, L.; Song, Y.; Zheng, X.; Cao, F.; Cao, S. Benzoxazine Monomer Derived Carbon Dots as a Broad-Spectrum Agent to Block Viral Infectivity. J. Colloid Interface Sci. 2019, 542, 198– 206, DOI: 10.1016/j.jcis.2019.02.01078https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXislOgs7Y%253D&md5=7c9871dbbe6c29af794aa35101000c71Benzoxazine monomer derived carbon dots as a broad-spectrum agent to block viral infectivityHuang, Shaomei; Gu, Jiangjiang; Ye, Jing; Fang, Bin; Wan, Shengfeng; Wang, Caoyu; Ashraf, Usama; Li, Qi; Wang, Xugang; Shao, Lin; Song, Yunfeng; Zheng, Xinsheng; Cao, Feifei; Cao, ShengboJournal of Colloid and Interface Science (2019), 542 (), 198-206CODEN: JCISA5; ISSN:0021-9797. (Elsevier B.V.)Multiple viruses can cause infection and death of millions annually. Of these, flaviviruses are found to be highly prevalent in recent years with no distinctive antiviral therapies. Therefore, there is a desperate need for broad-spectrum antiviral drugs that can be active against a large no. of existing and emerging viruses. Herein, we prepd. a kind of benzoxazine monomer derived carbon dots (BZM-CDs) and demonstrated their infection-blocking ability against life-threatening flaviviruses (Japanese encephalitis, Zika, and dengue viruses) and non-enveloped viruses (porcine parvovirus and adenovirus-assocd. virus). It was found that BZM-CDs could directly bind to the surface of the virion, and eventually the first step of virus-cell interaction was impeded. The developed nanoparticles are active against both flaviviruses and non-enveloped viruses in vitro. Thus, the application of BZM-CDs may constitute an intriguing broad-spectrum approach to rein in viral infections.
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79Zoppe, J. O.; Ruottinen, V.; Ruotsalainen, J.; Rönkkö, S.; Johansson, L.-S.; Hinkkanen, A.; Järvinen, K.; Seppälä, J. Synthesis of Cellulose Nanocrystals Carrying Tyrosine Sulfate Mimetic Ligands and Inhibition of Alphavirus Infection. Biomacromolecules 2014, 15, 1534– 1542, DOI: 10.1021/bm500229d79https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXktlSqs7o%253D&md5=5d947eb13327f3e7e8af8db90f6fac24Synthesis of Cellulose Nanocrystals Carrying Tyrosine Sulfate Mimetic Ligands and Inhibition of Alphavirus InfectionZoppe, Justin O.; Ruottinen, Ville; Ruotsalainen, Janne; Ronkko, Seppo; Johansson, Leena-Sisko; Hinkkanen, Ari; Jarvinen, Kristiina; Seppala, JukkaBiomacromolecules (2014), 15 (4), 1534-1542CODEN: BOMAF6; ISSN:1525-7797. (American Chemical Society)We present two facile approaches for introducing multivalent displays of tyrosine sulfate mimetic ligands on the surface of cellulose nanocrystals (CNCs) for application as viral inhibitors. We tested the efficacy of cellulose nanocrystals, prepd. either from cotton fibers or Whatman filter paper, to inhibit alphavirus infectivity in Vero (B) cells. Cellulose nanocrystals were produced by sulfuric acid hydrolysis leading to nanocrystal surfaces decorated with anionic sulfate groups. When the fluorescent marker expressing Semliki Forest virus vector, VA7-EGFP, was incubated with CNCs, strong inhibition of virus infectivity was achieved, up to 100 and 88% for cotton and Whatman CNCs, resp. When surface sulfate groups of CNCs were exchanged for tyrosine sulfate mimetic groups (i.e. Ph sulfonates), improved viral inhibition was attained. Our observations suggest that the conjugation of target-specific functionalities to CNC surfaces provides a means to control their antiviral activity. Multivalent CNCs did not cause observable in vitro cytotoxicity to Vero (B) cells or human corneal epithelial (HCE-T) cells, even within the 100% virus-inhibitory concns. Based on the similar chem. of known polyanionic inhibitors, our results suggest the potential application of CNCs as inhibitors of other viruses, such as human immunodeficiency virus (HIV) and herpes simplex viruses.
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80Lima, T. L. C.; Feitosa, R. D. C.; Dos Santos-Silva, E.; Dos Santos-Silva, A. M.; Siqueira, E. M. D. S.; Machado, P. R. L.; Cornélio, A. M.; Do Egito, E. S. T.; Fernandes-Pedrosa, M. D. F.; Farias, K. J. S.; Da Silva-Júnior, A. A. Improving Encapsulation of Hydrophilic Chloroquine Diphosphate into Biodegradable Nanoparticles: A Promising Approach against Herpes Virus Simplex-1 Infection. Pharmaceutics 2018, 10, 255, DOI: 10.3390/pharmaceutics1004025580https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXitFWktLnI&md5=f20bc5723458023af61f77f41575557fImproving encapsulation of hydrophilic chloroquine diphosphate into biodegradable nanoparticles: a promising approach against herpes virus simplex-1 infectionLima, Tabata Loise Cunha; de Carvalho Feitosa, Renata; dos Santos-Silva, Emanuell; dos Santos-Silva, Alaine Maria; da Silva Siqueira, Emerson Michell; Machado, Paula Renata Lima; Cornelio, Alianda Maira; do Egito, Eryvaldo Socrates Tabosa; de Freitas Fernandes-Pedrosa, Matheus; Farias, Kleber Juvenal Silva; da Silva-Junior, Arnobio AntonioPharmaceutics (2018), 10 (4), 255CODEN: PHARK5; ISSN:1999-4923. (MDPI AG)Chloroquine diphosphate (CQ) is a hydrophilic drug with low entrapment efficiency in hydrophobic nanoparticles (NP). Herpes simplex virus type 1 (HSV-1) is an enveloped double-stranded DNA virus worldwide known as a common human pathogen. This study aims to develop chloroquine-loaded poly(lactic acid) (PLA) nanoparticles (CQ-NP) to improve the chloroquine anti- HSV-1 efficacy. CQ-NP were successfully prepd. using a modified emulsification-solvent evapn. method. Physicochem. properties of the NP were monitored using dynamic light scattering, at. force microscopy, drug loading efficiency, and drug release studies. Spherical nanoparticles were produced with modal diam. of <300 nm, zeta potential of -20 mv and encapsulation efficiency of 64.1%. In vitro assays of CQ-NP performed in Vero E6 cells, using the MTT-assay, revealed different cytotoxicity levels. Blank nanoparticles (B-NP) were biocompatible. Finally, the antiviral activity tested by the plaque redn. assay revealed greater efficacy for CQ-NP compared to CQ at concns. equal to or lower than 20 μg mL-1 (p < 0.001). On the other hand, the B-NP had no antiviral activity. The CQ-NP has shown feasible properties and great potential to improve the antiviral activity of drugs.
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81Kong, B.; Moon, S.; Kim, Y.; Heo, P.; Jung, Y.; Yu, S.-H.; Chung, J.; Ban, C.; Kim, Y. H.; Kim, P.; Hwang, B. J.; Chung, W.-J.; Shin, Y.-K.; Seong, B. L.; Kweon, D.-H. Virucidal Nano-Perforator of Viral Membrane Trapping Viral Rnas in the Endosome. Nat. Commun. 2019, 10, 185, DOI: 10.1038/s41467-018-08138-181https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3cjhsVWisQ%253D%253D&md5=1c175360d72ec1b439569abcb71d1708Virucidal nano-perforator of viral membrane trapping viral RNAs in the endosomeKong Byoungjae; Moon Seokoh; Kim Yuna; Heo Paul; Jung Younghun; Yu Seok-Hyeon; Chung Jinhyo; Ban Choongjin; Chung Woo-Jae; Kweon Dae-Hyuk; Kim Yong Ho; Kweon Dae-Hyuk; Kim Paul; Hwang Beom Jeung; Seong Baik Lin; Shin Yeon-KyunNature communications (2019), 10 (1), 185 ISSN:.Membrane-disrupting agents that selectively target virus versus host membranes could potentially inhibit a broad-spectrum of enveloped viruses, but currently such antivirals are lacking. Here, we develop a nanodisc incorporated with a decoy virus receptor that inhibits virus infection. Mechanistically, nanodiscs carrying the viral receptor sialic acid bind to influenza virions and are co-endocytosed into host cells. At low pH in the endosome, the nanodiscs rupture the viral envelope, trapping viral RNAs inside the endolysosome for enzymatic decomposition. In contrast, liposomes containing a decoy receptor show weak antiviral activity due to the lack of membrane disruption. The nanodiscs inhibit influenza virus infection and reduce morbidity and mortality in a mouse model. Our results suggest a new class of antivirals applicable to other enveloped viruses that cause irreversible physical damage specifically to virus envelope by viruses' own fusion machine. In conclusion, the lipid nanostructure provides another dimension for antiviral activity of decoy molecules.
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82Hoffmann, M.; Kleine-Weber, H.; Schroeder, S.; Krüger, N.; Herrler, T.; Erichsen, S.; Schiergens, T. S.; Herrler, G.; Wu, N.-H.; Nitsche, A.; Müller, M. A.; Drosten, C.; Pöhlmann, S. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell 2020, 181, 271– 280, DOI: 10.1016/j.cell.2020.02.05282https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXktl2qtb8%253D&md5=60aea5c939a2d4df034a91d6198fb3efSARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease InhibitorHoffmann, Markus; Kleine-Weber, Hannah; Schroeder, Simon; Krueger, Nadine; Herrler, Tanja; Erichsen, Sandra; Schiergens, Tobias S.; Herrler, Georg; Wu, Nai-Huei; Nitsche, Andreas; Mueller, Marcel A.; Drosten, Christian; Poehlmann, StefanCell (Cambridge, MA, United States) (2020), 181 (2), 271-280.e8CODEN: CELLB5; ISSN:0092-8674. (Cell Press)The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clin. use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.
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83Ou, X.; Liu, Y.; Lei, X.; Li, P.; Mi, D.; Ren, L.; Guo, L.; Guo, R.; Chen, T.; Hu, J.; Xiang, Z.; Mu, Z.; Chen, X.; Chen, J.; Hu, K.; Jin, Q.; Wang, J.; Qian, Z. Characterization of Spike Glycoprotein of SARS-CoV-2 on Virus Entry and Its Immune Cross-Reactivity with SARS-CoV. Nat. Commun. 2020, 11, 1620, DOI: 10.1038/s41467-020-15562-983https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXlvFyjt78%253D&md5=6b0b1ef5a68f4a35da4aabecb0f99544Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoVOu, Xiuyuan; Liu, Yan; Lei, Xiaobo; Li, Pei; Mi, Dan; Ren, Lili; Guo, Li; Guo, Ruixuan; Chen, Ting; Hu, Jiaxin; Xiang, Zichun; Mu, Zhixia; Chen, Xing; Chen, Jieyong; Hu, Keping; Jin, Qi; Wang, Jianwei; Qian, ZhaohuiNature Communications (2020), 11 (1), 1620CODEN: NCAOBW; ISSN:2041-1723. (Nature Research)Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002-2003, MERS-CoV in 2012, and the newly emerged SARS-CoV-2 in late 2019. However, little is currently known about the biol. of SARS-CoV-2. Here, using SARS-CoV-2 S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) is the receptor for SARS-CoV-2, find that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L are crit. for entry, and that SARS-CoV-2 S protein is less stable than SARS-CoV S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry of SARS-CoV S but not SARS-CoV-2 S pseudovirions. Further studies using recovered SARS and COVID-19 patients' sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for SARS-CoV-2.
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84Wang, Q.; Zhang, Y.; Wu, L.; Niu, S.; Song, C.; Zhang, Z.; Lu, G.; Qiao, C.; Hu, Y.; Yuen, K.-Y.; Wang, Q.; Zhou, H.; Yan, J.; Qi, J. Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2. Cell 2020, 181, 894– 904, DOI: 10.1016/j.cell.2020.03.04584https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXmvFGrur4%253D&md5=188108e44f104860d4a2b83707ce7230Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2Wang, Qihui; Zhang, Yanfang; Wu, Lili; Niu, Sheng; Song, Chunli; Zhang, Zengyuan; Lu, Guangwen; Qiao, Chengpeng; Hu, Yu; Yuen, Kwok-Yung; Wang, Qisheng; Zhou, Huan; Yan, Jinghua; Qi, JianxunCell (Cambridge, MA, United States) (2020), 181 (4), 894-904.e9CODEN: CELLB5; ISSN:0092-8674. (Cell Press)The recent emergence of a novel coronavirus (SARS-CoV-2) in China has caused significant public health concerns. Recently, ACE2 was reported as an entry receptor for SARS-CoV-2. In this study, we present the crystal structure of the C-terminal domain of SARS-CoV-2 (SARS-CoV-2-CTD) spike (S) protein in complex with human ACE2 (hACE2), which reveals a hACE2-binding mode similar overall to that obsd. for SARS-CoV. However, at. details at the binding interface demonstrate that key residue substitutions in SARS-CoV-2-CTD slightly strengthen the interaction and lead to higher affinity for receptor binding than SARS-RBD. Addnl., a panel of murine monoclonal antibodies (mAbs) and polyclonal antibodies (pAbs) against SARS-CoV-S1/receptor-binding domain (RBD) were unable to interact with the SARS-CoV-2 S protein, indicating notable differences in antigenicity between SARS-CoV and SARS-CoV-2. These findings shed light on the viral pathogenesis and provide important structural information regarding development of therapeutic countermeasures against the emerging virus.
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85Hu, T. Y.; Frieman, M.; Wolfram, J. Insights from Nanomedicine into Chloroquine Efficacy against Covid-19. Nat. Nanotechnol. 2020, 15, 247– 249, DOI: 10.1038/s41565-020-0674-985https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXlsVeitbc%253D&md5=5982dadec9e67ff2201836264a82a858Insights from nanomedicine into chloroquine efficacy against COVID-19Hu, Tony Y.; Frieman, Matthew; Wolfram, JoyNature Nanotechnology (2020), 15 (4), 247-249CODEN: NNAABX; ISSN:1748-3387. (Nature Research)A review. Chloroquine - an approved malaria drug - is known in nanomedicine research for the investigation of nanoparticle uptake in cells, and may have potential for the treatment of COVID-19.
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86Iannazzo, D.; Pistone, A.; Ferro, S.; De Luca, L.; Monforte, A. M.; Romeo, R.; Buemi, M. R.; Pannecouque, C. Graphene Quantum Dots Based Systems as HIV Inhibitors. Bioconjugate Chem. 2018, 29, 3084– 3093, DOI: 10.1021/acs.bioconjchem.8b0044886https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhsV2lsLjK&md5=fe5063bada938f85bc6214a6cab5d928Graphene Quantum Dots Based Systems As HIV InhibitorsIannazzo, Daniela; Pistone, Alessandro; Ferro, Stefania; De Luca, Laura; Monforte, Anna Maria; Romeo, Roberto; Buemi, Maria Rosa; Pannecouque, ChristopheBioconjugate Chemistry (2018), 29 (9), 3084-3093CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)Graphene quantum dots (GQD) are the next generation of nanomaterials with great potential in drug delivery and target-specific HIV inhibition. In this study we investigated the antiviral activity of graphene based nanomaterials by using water-sol. GQD synthesized from multiwalled carbon nanotubes (MWCNT) through prolonged acidic oxidn. and exfoliation and compared their anti-HIV activity with that exerted by reverse transcriptase inhibitors (RTI) conjugated with the same nanomaterial. The antiretroviral agents chosen in this study, CHI499 and CDF119, belong to the class of non-nucleoside reverse transcriptase inhibitors (NNRTI). From this study emerged the RTI-conjugated compd. GQD-CHI499 as a good potential candidate for HIV treatment, showing an IC50 of 0.09 μg/mL and an EC50 value in cell of 0.066 μg/mL. The target of action in the replicative cycle of HIV of the drug conjugated samples GQD-CHI499 and GQD-CDF119 was also investigated by a time of addn. (TOA) method, showing for both conjugated samples a mechanism of action similar to that exerted by NNRTI drugs.
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87Galdiero, S.; Falanga, A.; Vitiello, M.; Cantisani, M.; Marra, V.; Galdiero, M. Silver Nanoparticles as Potential Antiviral Agents. Molecules 2011, 16, 8894– 8918, DOI: 10.3390/molecules1610889487https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhsVOqurrK&md5=a41d01ceef275d779deb1509c0ab6fefSilver nanoparticles as potential antiviral agentsGaldiero, Stefania; Falanga, Annarita; Vitiello, Mariateresa; Cantisani, Marco; Marra, Veronica; Galdiero, MassimilianoMolecules (2011), 16 (), 8894-8918CODEN: MOLEFW; ISSN:1420-3049. (MDPI AG)A review. Virus infections pose significant global health challenges, esp. in view of the fact that the emergence of resistant viral strains and the adverse side effects assocd. with prolonged use continue to slow down the application of effective antiviral therapies. This makes imperative the need for the development of safe and potent alternatives to conventional antiviral drugs. In the present scenario, nanoscale materials have emerged as novel antiviral agents for the possibilities offered by their unique chem. and phys. properties. Silver nanoparticles have mainly been studied for their antimicrobial potential against bacteria, but have also proven to be active against several types of viruses including human immunodeficiency virus, hepatitis B virus, herpes simplex virus, respiratory syncytial virus, and monkey pox virus. The use of metal nanoparticles provides an interesting opportunity for novel antiviral therapies. Since metals may attack a broad range of targets in the virus there is a lower possibility to develop resistance as compared to conventional antivirals. The present review focuses on the development of methods for the prodn. of silver nanoparticles and on their use as antiviral therapeutics against pathogenic viruses.
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88Yen, H.-J.; Hsu, S.-H.; Tsai, C.-L. Cytotoxicity and Immunological Response of Gold and Silver Nanoparticles of Different Sizes. Small 2009, 5, 1553– 1561, DOI: 10.1002/smll.20090012688https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXos1Cqt7o%253D&md5=e1a847ba1093bce4dba630df403e1bffCytotoxicity and immunological response of gold and silver nanoparticles of different sizesYen, Hung-Jen; Hsu, Shan-hui; Tsai, Ching-LinSmall (2009), 5 (13), 1553-1561CODEN: SMALBC; ISSN:1613-6810. (Wiley-VCH Verlag GmbH & Co. KGaA)The immunol. response of macrophages to phys. produced pure Au and Ag nanoparticles (NPs) (in 3 different sizes) is investigated in vitro. The treatment of either type of NP at ≥10 ppm dramatically decreases the population and increases the size of the macrophages. Both NPs enter the cells but only AuNPs (esp. those with smaller diam.) up-regulate the expressions of proinflammatory genes interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF-α). Transmission electron microscopy images show that AuNPs and AgNPs are both trapped in vesicles in the cytoplasm, but only AuNPs are organized into a circular pattern. It is speculated that part of the neg. charged AuNPs might adsorb serum protein and enter cells via the more complicated endocytotic pathway, which results in higher cytotoxicity and immunol. response of AuNPs as compared to AgNPS.
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89Johnston, H. J.; Hutchison, G.; Christensen, F. M.; Peters, S.; Hankin, S.; Stone, V. A Review of the In Vivo and In Vitro Toxicity of Silver and Gold Particulates: Particle Attributes and Biological Mechanisms Responsible for the Observed Toxicity. Crit. Rev. Toxicol. 2010, 40, 328– 346, DOI: 10.3109/1040844090345307489https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXjsFeguro%253D&md5=bb89818ce201ff712139ef70cd118bb1A review of the in vivo and in vitro toxicity of silver and gold particulates: Particle attributes and biological mechanisms responsible for the observed toxicityJohnston, Helinor J.; Hutchison, Gary; Christensen, Frans M.; Peters, Sheona; Hankin, Steve; Stone, VickiCritical Reviews in Toxicology (2010), 40 (4), 328-346CODEN: CRTXB2; ISSN:1040-8444. (Informa Healthcare)A review. This review is concerned with evaluating the toxicity assocd. with human exposure to silver and gold nanoparticles (NPs), due to the relative abundance of toxicity data available for these particles, when compared to other metal particulates. This has allowed knowledge on the current understanding of the field to be gained, and has demonstrated where gaps in knowledge are. It is anticipated that evaluating the hazards assocd. with silver and gold particles will ultimately enable risk assessments to be completed, by combining this information with knowledge on the level of human exposure. The quantity of available hazard information for metals is greatest for silver particulates, due to its widespread inclusion within a no. of diverse products (including clothes and wound dressings), which primarily arises from its antibacterial behavior. Gold has been used on numerous occasions to assess the biodistribution and cellular uptake of NPs following exposure. Inflammatory, oxidative, genotoxic, and cytotoxic consequences are assocd. with silver particulate exposure, and are inherently linked. The primary site of gold and silver particulate accumulation has been consistently demonstrated to be the liver, and it is therefore relevant that a no. of in vitro investigations have focused on this potential target organ. However, in general there is a lack of in vivo and in vitro toxicity information that allows correlations between the findings to be made. Instead a focus on the tissue distribution of particles following exposure is evident within the available literature, which can be useful in directing appropriate in vitro experimentation by revealing potential target sites of toxicity. The exptl. design has the potential to impact on the toxicol. observations, and in particular the use of excessively high particle concns. has been obsd. As witnessed for other particle types, gold and silver particle sizes are influential in dictating the obsd. toxicity, with smaller particles exhibiting a greater response than their larger counterparts, and this is likely to be driven by differences in particle surface area, when administered at an equal-mass dose. A major obstacle, at present, is deciphering whether the responses related to silver nanoparticulate exposure derive from their small size, or particle dissoln. contributes to the obsd. toxicity. Alternatively, a combination of both may be responsible, as the release of ions would be expected to be greater for smaller particles.
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90Bar-Ilan, O.; Albrecht, R. M.; Fako, V. E.; Furgeson, D. Y. Toxicity Assessments of Multisized Gold and Silver Nanoparticles in Zebrafish Embryos. Small 2009, 5, 1897– 1910, DOI: 10.1002/smll.20080171690https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXps1ykurg%253D&md5=8703eb895b5cae658bfc6fd191de1decToxicity Assessments of Multisized Gold and Silver Nanoparticles in Zebrafish EmbryosBar-Ilan, Ofek; Albrecht, Ralph M.; Fako, Valerie E.; Furgeson, Darin Y.Small (2009), 5 (16), 1897-1910CODEN: SMALBC; ISSN:1613-6810. (Wiley-VCH Verlag GmbH & Co. KGaA)The potential toxicity of nanoparticles is addressed by utilizing a putative attractive model in developmental biol. and genetics: the zebrafish (Danio rerio). Transparent zebrafish embryos, possessing a high degree of homol. to the human genome, offer an economically feasible, medium-throughput screening platform for noninvasive real-time assessments of toxicity. Using colloidal silver (cAg) and gold nanoparticles (cAu) in a panoply of sizes (3, 10, 50, and 100 nm) and a semiquant. scoring system, it is found that cAg produces almost 100% mortality at 120 h post-fertilization, while cAu produces less than 3% mortality at the same time point. Furthermore, while cAu induces minimal sublethal toxic effects, cAg treatments generate a variety of embryonic morphol. malformations. Both cAg and cAu are taken up by the embryos and control expts., suggesting that cAg toxicity is caused by the nanoparticles themselves or Ag+ that is formed during in vivo nanoparticle destabilization. Although cAg toxicity is slightly size dependent at certain concns. and time points, the most striking result is that parallel sizes of cAg and cAu induce significantly different toxic profiles, with the former being toxic and the latter being inert in all exposed sizes. Therefore, it is proposed that nanoparticle chem. is as, if not more, important than specific nanosizes at inducing toxicity in vivo. Ultimately such assessments using the zebrafish embryo model should lead to the identification of nanomaterial characteristics that afford minimal or no toxicity and guide more rational designs of materials on the nanoscale.
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91Li, Y.; Lin, Z.; Gong, G.; Guo, M.; Xu, T.; Wang, C.; Zhao, M.; Xia, Y.; Tang, Y.; Zhong, J.; Chen, Y.; Hua, L.; Huang, Y.; Zeng, F.; Zhu, B. Inhibition of H1N1 Influenza Virus-Induced Apoptosis by Selenium Nanoparticles Functionalized with Arbidol through ROS-Mediated Signaling Pathways. J. Mater. Chem. B 2019, 7, 4252– 4262, DOI: 10.1039/C9TB00531E91https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtVOgtLbE&md5=f38cb73793e9c38f152aeb674ae946d2Inhibition of H1N1 influenza virus-induced apoptosis by selenium nanoparticles functionalized with arbidol through ROS-mediated signaling pathwaysLi, Yinghua; Lin, Zhengfang; Gong, Guifang; Guo, Min; Xu, Tiantian; Wang, Changbing; Zhao, Mingqi; Xia, Yu; Tang, Ying; Zhong, Jiayu; Chen, Yi; Hua, Liang; Huang, Yanqing; Zeng, Fangling; Zhu, BingJournal of Materials Chemistry B: Materials for Biology and Medicine (2019), 7 (27), 4252-4262CODEN: JMCBDV; ISSN:2050-7518. (Royal Society of Chemistry)As an effective antiviral agent, the clin. application of arbidol is limited by the appearance of drug-resistant viruses. To overcome the limitation of drug-resistance, the use of modified nanoparticles with biol. materials to explore novel anti-influenza drugs is developing rapidly. The antiviral activity of selenium nanoparticles (SeNPs) has attracted increasing attention in the biomedical field. Surface modified SeNPs by arbidol (Se@ARB) with superior antiviral properties towards drug resistance are synthesized in the current study. Arbidol decoration of SeNPs (Se@ARB) with less toxicity had obviously inhibited H1N1 infection. Se@ARB interfered with the interaction between the H1N1 influenza virus and the host cells by suppressing the activity of hemagglutinin (HA) and neuraminidase (NA). Se@ARB could prevent H1N1 from infecting MDCK cells and block DNA fragmentation and chromatin condensation. Furthermore, Se@ARB evidently inhibited the generation of reactive oxygen species (ROS). In vivo expts. revealed that Se@ARB prevents lung injury in H1N1 infected mice through hematoxylin and eosin staining. The TUNEL test of lung tissues shows that DNA damage reached a high level but reduced substantially when treated with Se@ARB. Immunohistochem. assay revealed that activation of caspase-3, AKT and MAPK signaling pathways was restrained by Se@ARB treatment. These results demonstrate that Se@ARB is a promising antiviral pharmaceutical candidate for the inhibition of H1N1 influenza virus.
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92Milewska, A.; Kaminski, K.; Ciejka, J.; Kosowicz, K.; Zeglen, S.; Wojarski, J.; Nowakowska, M.; Szczubiałka, K.; Pyrc, K. HTCC: Broad Range Inhibitor of Coronavirus Entry. PLoS One 2016, 11, e0156552, DOI: 10.1371/journal.pone.015655292https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhsFKhsb%252FK&md5=a6037aafdf3c7e162b40bb92abcfc822HTCC: broad range inhibitor of coronavirus entryMilewska, Aleksandra; Kaminski, Kamil; Ciejka, Justyna; Kosowicz, Katarzyna; Zeglen, Slawomir; Wojarski, Jacek; Nowakowska, Maria; Szczubialka, Krzysztof; Pyrc, KrzysztofPLoS One (2016), 11 (6), e0156552/1-e0156552/17CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)To date, six human coronaviruses have been known, all of which are assocd. with respiratory infections in humans. With the exception of the highly pathogenic SARS and MERS coronaviruses, human coronaviruses (HCoV-NL63, HCoV-OC43, HCoV-229E, and HCoVHKU1) circulate worldwide and typically cause the common cold. In most cases, infection with these viruses does not lead to severe disease, although acute infections in infants, the elderly, and immunocompromised patients may progress to severe disease requiring hospitalization. Importantly, no drugs against human coronaviruses exist, and only supportive therapy is available. Previously, we proposed the cationically modified chitosan, N-(2- hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC), and its hydrophobicallymodified deriv. (HM-HTCC) as potent inhibitors of the coronavirus HCoV-NL63. Here, we show that HTCC inhibits interaction of a virus with its receptor and thus blocks the entry. Further, we demonstrate that HTCC polymers with different degrees of substitution act as effective inhibitors of all low-pathogenic human coronaviruses.
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93Raghuwanshi, D.; Mishra, V.; Das, D.; Kaur, K.; Suresh, M. R. Dendritic Cell Targeted Chitosan Nanoparticles for Nasal DNA Immunization against SARS CoV Nucleocapsid Protein. Mol. Pharmaceutics 2012, 9, 946– 956, DOI: 10.1021/mp200553x93https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XislSkt7Y%253D&md5=b5b666a5b8222807266e06bc79fbfd36Dendritic Cell Targeted Chitosan Nanoparticles for Nasal DNA Immunization against SARS CoV Nucleocapsid ProteinRaghuwanshi, Dharmendra; Mishra, Vivek; Das, Dipankar; Kaur, Kamaljit; Suresh, Mavanur R.Molecular Pharmaceutics (2012), 9 (4), 946-956CODEN: MPOHBP; ISSN:1543-8384. (American Chemical Society)This work investigates the formulation and in vivo efficacy of dendritic cell (DC) targeted plasmid DNA loaded biotinylated chitosan nanoparticles for nasal immunization against nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) as antigen. The induction of antigen-specific mucosal and systemic immune response at the site of virus entry is a major challenge for vaccine design. Here, we designed a strategy for noninvasive receptor mediated gene delivery to nasal resident DCs. The pDNA loaded biotinylated chitosan nanoparticles were prepd. using a complex coacervation process and characterized for size, shape, surface charge, plasmid DNA loading and protection against nuclease digestion. The pDNA loaded biotinylated chitosan nanoparticles were targeted with bifunctional fusion protein (bfFp) vector for achieving DC selective targeting. The bfFp is a recombinant fusion protein consisting of truncated core-streptavidin fused with anti-DEC-205 single chain antibody (scFv). The core-streptavidin arm of fusion protein binds with biotinylated nanoparticles, while anti-DEC-205 scFv imparts targeting specificity to DC DEC-205 receptor. We demonstrate that intranasal administration of bfFp targeted formulations along with anti-CD40 DC maturation stimuli enhanced magnitude of mucosal IgA as well as systemic IgG against N protein. The strategy led to the detection of augmented levels of N protein specific systemic IgG and nasal IgA antibodies. However, following intranasal delivery of naked pDNA no mucosal and systemic immune responses were detected. A parallel comparison of targeted formulations using i.m. and intranasal routes showed that the i.m. route is superior for induction of systemic IgG responses compared with the intranasal route. Our results suggest that targeted pDNA delivery through a noninvasive intranasal route can be a strategy for designing low-dose vaccines.
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94Alghrair, Z. K.; Fernig, D. G.; Ebrahimi, B. Enhanced Inhibition of Influenza Virus Infection by Peptide-Noble-Metal Nanoparticle Conjugates. Beilstein J. Nanotechnol. 2019, 10, 1038– 1047, DOI: 10.3762/bjnano.10.10494https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtVGgtLrF&md5=67095809fbd256a6a9109040860cb7f8Enhanced inhibition of influenza virus infection by peptide-noble-metal nanoparticle conjugatesAlghrair, Zaid K.; Fernig, David G.; Ebrahimi, BahramBeilstein Journal of Nanotechnology (2019), 10 (), 1038-1047CODEN: BJNEAH; ISSN:2190-4286. (Beilstein-Institut zur Foerderung der Chemischen Wissenschaften)We have explored the potential for noble-metal nanoparticle conjugates of FluPep to enhance its antiviral activity and to det. their potential as a delivery platform for FluPep. FluPep ligand is FluPep extended at its N-terminus with the sequence CVVVTAAA, to allow for its incorporation into a mixed-matrix ligand shell of a peptidol and an alkanethiol ethylene glycol consisting of 70% CVVVTol and 30% HS(CH2)11 (OC2H4)4OH (mol/mol). Gold and silver nanoparticles (ca. 10 nm diam.) with up to 5% (mol/mol) FluPep ligand remained as stable as the control of mixed-matrix-passivated nanoparticles in a variety of tests, including ligand exchange with dithiothreitol. The free FluPep ligand peptide was found to inhibit viral plaque formation in canine MDCK cells (IC50 = 2.1 nM), but was less potent than FluPep itself (IC50 = 140 pM). Nanoparticles functionalised with FluPep ligand showed enhanced antiviral activity compared to the free peptides. The IC50 value of the FluPep-functionalised nanoparticles decreased as the grafting d. of FluPep ligand increased from 0.03% to 5% (both mol/mol), with IC50 values down to about 10% of that of the corresponding free peptide. The data demonstrate that conjugation of FluPep to gold and silver nanoparticles enhances its antiviral potency; the antimicrobial activity of silver ions may enable the design of even more potent antimicrobial inhibitors, capable of targeting both influenza and bacterial co-infections.
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95Mori, Y.; Ono, T.; Miyahira, Y.; Nguyen, V. Q.; Matsui, T.; Ishihara, M. Antiviral Activity of Silver Nanoparticle/Chitosan Composites against H1n1 Influenza a Virus. Nanoscale Res. Lett. 2013, 8, 93– 93, DOI: 10.1186/1556-276X-8-9395https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXht1Wisb7K&md5=1eb2644efd696c62ed295f8ee0d5d88cAntiviral activity of silver nanoparticle/chitosan composites against H1N1 influenza A virusMori, Yasutaka; Ono, Takeshi; Miyahira, Yasushi; Nguyen, Vinh Quang; Matsui, Takemi; Ishihara, MasayukiNanoscale Research Letters (2013), 8 (1), 93/1-93/6CODEN: NRLAAD; ISSN:1556-276X. (Springer)Silver nanoparticle (Ag NP)/chitosan (Ch) composites with antiviral activity against H1N1 influenza A virus were prepd. The Ag NP/Ch composites were obtained as yellow or brown floc-like powders following reaction at room temp. in aq. medium. Ag NPs (3.5, 6.5, and 12.9 nm av. diams.) were embedded into the chitosan matrix without aggregation or size alternation. The antiviral activity of the Ag NP/Ch composites was evaluated by comparing the TCID50 ratio of viral suspensions treated with the composites to untreated suspensions. For all sizes of Ag NPs tested, antiviral activity against H1N1 influenza A virus increased as the concn. of Ag NPs increased; chitosan alone exhibited no antiviral activity. Size dependence of the Ag NPs on antiviral activity was also obsd.: antiviral activity was generally stronger with smaller Ag NPs in the composites. These results indicate that Ag NP/Ch composites interacting with viruses exhibit antiviral activity.
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96Du, T.; Lu, J.; Liu, L.; Dong, N.; Fang, L.; Xiao, S.; Han, H. Antiviral Activity of Graphene Oxide–Silver Nanocomposites by Preventing Viral Entry and Activation of the Antiviral Innate Immune Response. ACS Appl. Bio Mater. 2018, 1, 1286– 1293, DOI: 10.1021/acsabm.8b0015496https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXitVansbrM&md5=b04d516c949e51fbd322afc4d8c18677Antiviral Activity of Graphene Oxide-Silver Nanocomposites by Preventing Viral Entry and Activation of the Antiviral Innate Immune ResponseDu, Ting; Lu, Jian; Liu, Lingzhi; Dong, Nan; Fang, Liurong; Xiao, Shaobo; Han, HeyouACS Applied Bio Materials (2018), 1 (5), 1286-1293CODEN: AABMCB; ISSN:2576-6422. (American Chemical Society)Developing nanomaterials-based antimicrobial agents has shown a widespread promise. In this study, silver nanoparticle-modified graphene oxide (GO-AgNPs) nanocomposites were self-assembled via interfacial electrostatic force. By using the porcine reproductive and respiratory syndrome virus (PRRSV) as a pattern, the antiviral effect of the as-prepd. GO-AgNPs nanocomposites on the replication of virus was investigated. The results indicated that exposure with GO-AgNPs nanocomposites could obviously suppress PRRSV infection. It was found that GO-AgNPs nanocomposites exhibited a better inhibitory effect compared with AgNPs and GO. By selecting the porcine epidemic diarrhea virus (PEDV) as a contrast virus, GO-AgNPs nanocomposites were proven to have a broad antiviral activity. Mechanism studies showed that GO-AgNPs nanocomposites might prevent PRRSV from entering the host cells, with 59.2% inhibition efficiency. Meanwhile, GO-AgNPs nanocomposite treatment enhances the prodn. of interferon-α (IFN-α) and IFN-stimulating genes (ISGs), which can directly inhibit the proliferation of virus. Taken together, this study reports a new type of antiviral agent and provides a promising pharmaceutical agent for treating infection by the highly pathogenic PRRSV. Moreover, it may provide novel ideas for the research and development of antiviral formulations based on nanocomposites and extend their applications in biol. systems.
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97Du, T.; Liang, J.; Dong, N.; Liu, L.; Fang, L.; Xiao, S.; Han, H. Carbon Dots as Inhibitors of Virus by Activation of Type I Interferon Response. Carbon 2016, 110, 278– 285, DOI: 10.1016/j.carbon.2016.09.03297https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhsFCmtLnF&md5=8807c9a8abb01c40df79ba928e03ae97Carbon dots as inhibitors of virus by activation of type I interferon responseDu, Ting; Liang, Jiangong; Dong, Nan; Liu, Lin; Fang, Liurong; Xiao, Shaobo; Han, HeyouCarbon (2016), 110 (), 278-285CODEN: CRBNAH; ISSN:0008-6223. (Elsevier Ltd.)Carbon dots (CDs) has shown exciting potential in the field of bioscience and biotechnol. due to their low toxicity, biol. and ecol. friendliness and desirable performance characteristics of quantum dots (QDs). However, the effects of CDs on viruses are still largely unknown. In this study, we investigate the effect of CDs on the replication of virus by using pseudorabies virus (PRV) and porcine reproductive and respiratory syndrome virus (PRRSV) as the models of DNA virus and RNA virus, resp. Analyses of virus titers and the expression of viral proteins demonstrate that cells treated with CDs can significantly inhibit the multiplication of PRV and PRRSV. In mechanism, CDs treatment dramatically induces interferon-α (IFN-α) prodn. and the expression of IFN-stimulating genes (ISGs) which in turn inhibits virus replication. Taken together, these results reveal a previously undefined role of CDs and provide a new strategy to develop antiviral agents.
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98Sharma, V.; Kaushik, S.; Pandit, P.; Dhull, D.; Yadav, J. P.; Kaushik, S. Green Synthesis of Silver Nanoparticles from Medicinal Plants and Evaluation of Their Antiviral Potential against Chikungunya Virus. Appl. Microbiol. Biotechnol. 2019, 103, 881– 891, DOI: 10.1007/s00253-018-9488-198https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXitFOjt7jL&md5=799fec3583ceb89e334815ce4d6859dcGreen synthesis of silver nanoparticles from medicinal plants and evaluation of their antiviral potential against chikungunya virusSharma, Vikrant; Kaushik, Sulochana; Pandit, Pooja; Dhull, Divya; Yadav, Jaya Parkash; Kaushik, SamanderApplied Microbiology and Biotechnology (2019), 103 (2), 881-891CODEN: AMBIDG; ISSN:0175-7598. (Springer)The exploration of nanoscale materials for their therapeutic potential against emerging and re-emerging infections has been increased in recent years. Silver nanoparticles (AgNPs) are known to possess antimicrobial activities against different pathogens including viruses and provide an excellent opportunity to develop new antivirals. The present study focused on biol. synthesis of AgNPs from Andrographis paniculata, Phyllanthus niruri, and Tinospora cordifolia and evaluation of their antiviral properties against chikungunya virus. Synthesized plants AgNPs were characterized to assess their formation, morphol., and stability. The cytotoxicity assays in Vero cells revealed that A. paniculata AgNPs were most cytotoxic with max. non-toxic dose (MNTD) value of 31.25μg/mL followed by P. niruri (MNTD, 125μg/mL) and T. cordifolia AgNPs (MNTD, 250μg/mL). In vitro antiviral assay of AgNPs based on degree of inhibition of cytopathic effect (CPE) showed that A. paniculata AgNPs were most effective, followed by T. cordifolia and P. niruri AgNPs. The results of antiviral assay were confirmed by cell viability test using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) dye, which revealed that A. paniculata AgNPs inhibited the virus to a max. extent. The cell viability of CHIKV-infected cells significantly increased from 25.69% to 80.76 and 66.8%, when treated with A. paniculata AgNPs at MNTD and 1/2MNTD, resp. These results indicated that use of plants AgNPs as antiviral agents is feasible and could provide alternative treatment options against viral diseases which have no specific antiviral or vaccines available yet.
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99Yang, X. X.; Li, C. M.; Huang, C. Z. Curcumin Modified Silver Nanoparticles for Highly Efficient Inhibition of Respiratory Syncytial Virus Infection. Nanoscale 2016, 8, 3040– 3048, DOI: 10.1039/C5NR07918G99https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XislKnsw%253D%253D&md5=8a288a70879432df568881c84b1d6046Curcumin modified silver nanoparticles for highly efficient inhibition of respiratory syncytial virus infectionYang, Xiao Xi; Li, Chun Mei; Huang, Cheng ZhiNanoscale (2016), 8 (5), 3040-3048CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)Interactions between nanoparticles and viruses have attracted increasing attention due to the antiviral activity of nanoparticles and the resulting possibility to be employed as biomedical interventions. In this contribution, we developed a very simple route to prep. uniform and stable silver nanoparticles (AgNPs) with antiviral properties by using curcumin, which is a member of the ginger family isolated from rhizomes of the perennial herb Curcuma longa and has a wide range of biol. activities like antioxidant, antifungal, antibacterial and anti-inflammatory effects, and acts as reducing and capping agents in this synthetic route. The tissue culture infectious dose (TCID50) assay showed that the curcumin modified silver nanoparticles (cAgNPs) have a highly efficient inhibition effect against respiratory syncytial virus (RSV) infection, giving a decrease of viral titers about two orders of magnitude at the concn. of cAgNPs under which no toxicity was found to the host cells. Mechanism investigations showed that cAgNPs could prevent RSV from infecting the host cells by inactivating the virus directly, indicating that cAgNPs are a novel promising efficient virucide for RSV.
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100Elechiguerra, J. L.; Burt, J. L.; Morones, J. R.; Camacho-Bragado, A.; Gao, X.; Lara, H. H.; Yacaman, M. J. Interaction of Silver Nanoparticles with HIV-1. J. Nanobiotechnol. 2005, 3, 6, DOI: 10.1186/1477-3155-3-6100https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD2MvltlGquw%253D%253D&md5=5489a919aa800a88e7dce2398d029494Interaction of silver nanoparticles with HIV-1Elechiguerra Jose Luis; Burt Justin L; Morones Jose R; Camacho-Bragado Alejandra; Gao Xiaoxia; Lara Humberto H; Yacaman Miguel JoseJournal of nanobiotechnology (2005), 3 (), 6 ISSN:.The interaction of nanoparticles with biomolecules and microorganisms is an expanding field of research. Within this field, an area that has been largely unexplored is the interaction of metal nanoparticles with viruses. In this work, we demonstrate that silver nanoparticles undergo a size-dependent interaction with HIV-1, with nanoparticles exclusively in the range of 1-10 nm attached to the virus. The regular spatial arrangement of the attached nanoparticles, the center-to-center distance between nanoparticles, and the fact that the exposed sulfur-bearing residues of the glycoprotein knobs would be attractive sites for nanoparticle interaction suggest that silver nanoparticles interact with the HIV-1 virus via preferential binding to the gp120 glycoprotein knobs. Due to this interaction, silver nanoparticles inhibit the virus from binding to host cells, as demonstrated in vitro.
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101Bowman, M.-C.; Ballard, T. E.; Ackerson, C. J.; Feldheim, D. L.; Margolis, D. M.; Melander, C. Inhibition of HIV Fusion with Multivalent Gold Nanoparticles. J. Am. Chem. Soc. 2008, 130, 6896– 6897, DOI: 10.1021/ja710321g101https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXlvFyrsr8%253D&md5=6defba3d410e679b11f1ee75efd8dda6Inhibition of HIV Fusion with Multivalent Gold NanoparticlesBowman, Mary-Catherine; Ballard, T. Eric; Ackerson, Christopher J.; Feldheim, Daniel L.; Margolis, David M.; Melander, ChristianJournal of the American Chemical Society (2008), 130 (22), 6896-6897CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)The design and synthesis of a multivalent gold nanoparticle therapeutic is presented. SDC-1721, a fragment of the potent HIV inhibitor TAK-779, was synthesized and conjugated to 2.0 nm diam. gold nanoparticles. Free SDC-1721 had no inhibitory effect on HIV infection; however, the (SDC-1721)-gold nanoparticle conjugates displayed activity comparable to that of TAK-779. This result suggests that multivalent presentation of small mols. on gold nanoparticle surfaces can convert inactive drugs into potent therapeutics.
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102Di Gianvincenzo, P.; Marradi, M.; Martínez-Ávila, O. M.; Bedoya, L. M.; Alcamí, J.; Penadés, S. Gold Nanoparticles Capped with Sulfate-Ended Ligands as Anti-HIV Agents. Bioorg. Med. Chem. Lett. 2010, 20, 2718– 2721, DOI: 10.1016/j.bmcl.2010.03.079102https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXkvFeqtbc%253D&md5=139966eefbcd5f9a04e36e83e0018aa1Gold nanoparticles capped with sulfate-ended ligands as anti-HIV agentsDi Gianvincenzo, Paolo; Marradi, Marco; Martinez-Avila, Olga Maria; Bedoya, Luis Miguel; Alcami, Jose; Penades, SoledadBioorganic & Medicinal Chemistry Letters (2010), 20 (9), 2718-2721CODEN: BMCLE8; ISSN:0960-894X. (Elsevier B.V.)Gold nanoparticles coated with multiple copies of an amphiphilic sulfate-ended ligand are able to bind the HIV envelope glycoprotein gp120 as measured by surface plasmon resonance (SPR) and inhibit in vitro the HIV infection of T-cells at nanomolar concns. A 50% d. of sulfated ligands on ∼2 nm nanoparticles (the other ligands being inert glucose derivs.) is enough to achieve high anti-HIV activities. This result opens up the possibility of tailoring both sulfated ligands and other anti-HIV mols. on the same gold cluster, thus contributing to the development of non-cocktail based multifunctional anti-HIV systems.
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103Rosemary Bastian, A.; Nangarlia, A.; Bailey, L. D.; Holmes, A.; Kalyana Sundaram, R. V.; Ang, C.; Moreira, D. R.; Freedman, K.; Duffy, C.; Contarino, M.; Abrams, C.; Root, M.; Chaiken, I. Mechanism of Multivalent Nanoparticle Encounter with HIV-1 for Potency Enhancement of Peptide Triazole Virus Inactivation. J. Biol. Chem. 2015, 290, 529– 543, DOI: 10.1074/jbc.M114.608315103https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2M3lslekug%253D%253D&md5=7052ac7786204d8e6328c83a8edc5b4cMechanism of multivalent nanoparticle encounter with HIV-1 for potency enhancement of peptide triazole virus inactivationRosemary Bastian Arangassery; Nangarlia Aakansha; Kalyana Sundaram R Venkat; Ang Charles; Bailey Lauren D; Holmes Andrew; Duffy Caitlin; Contarino Mark; Chaiken Irwin; Moreira Diogo R M; Freedman Kevin; Abrams Cameron; Root MichaelThe Journal of biological chemistry (2015), 290 (1), 529-43 ISSN:.Entry of HIV-1 into host cells remains a compelling yet elusive target for developing agents to prevent infection. A peptide triazole (PT) class of entry inhibitor has previously been shown to bind to HIV-1 gp120, suppress interactions of the Env protein at host cell receptor binding sites, inhibit cell infection, and cause envelope spike protein breakdown, including gp120 shedding and, for some variants, virus membrane lysis. We found that gold nanoparticle-conjugated forms of peptide triazoles (AuNP-PT) exhibit substantially more potent antiviral effects against HIV-1 than corresponding peptide triazoles alone. Here, we sought to reveal the mechanism of potency enhancement underlying nanoparticle conjugate function. We found that altering the physical properties of the nanoparticle conjugate, by increasing the AuNP diameter and/or the density of PT conjugated on the AuNP surface, enhanced potency of infection inhibition to impressive picomolar levels. Further, compared with unconjugated PT, AuNP-PT was less susceptible to reduction of antiviral potency when the density of PT-competent Env spikes on the virus was reduced by incorporating a peptide-resistant mutant gp120. We conclude that potency enhancement of virolytic activity and corresponding irreversible HIV-1 inactivation of PTs upon AuNP conjugation derives from multivalent contact between the nanoconjugates and metastable Env spikes on the HIV-1 virus. The findings reveal that multispike engagement can exploit the metastability built into virus the envelope to irreversibly inactivate HIV-1 and provide a conceptual platform to design nanoparticle-based antiviral agents for HIV-1 specifically and putatively for metastable enveloped viruses generally.
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104Speshock, J. L.; Murdock, R. C.; Braydich-Stolle, L. K.; Schrand, A. M.; Hussain, S. M. Interaction of Silver Nanoparticles with Tacaribe Virus. J. Nanobiotechnol. 2010, 8, 19, DOI: 10.1186/1477-3155-8-19104https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3cfhtF2htA%253D%253D&md5=32de5304b6d4301b44174cfb5432a313Interaction of silver nanoparticles with Tacaribe virusSpeshock Janice L; Murdock Richard C; Braydich-Stolle Laura K; Schrand Amanda M; Hussain Saber MJournal of nanobiotechnology (2010), 8 (), 19 ISSN:.BACKGROUND: Silver nanoparticles possess many unique properties that make them attractive for use in biological applications. Recently they received attention when it was shown that 10 nm silver nanoparticles were bactericidal, which is promising in light of the growing number of antibiotic resistant bacteria. An area that has been largely unexplored is the interaction of nanomaterials with viruses and the possible use of silver nanoparticles as an antiviral agent. RESULTS: This research focuses on evaluating the interaction of silver nanoparticles with a New World arenavirus, Tacaribe virus, to determine if they influence viral replication. Surprisingly exposing the virus to silver nanoparticles prior to infection actually facilitated virus uptake into the host cells, but the silver-treated virus had a significant reduction in viral RNA production and progeny virus release, which indicates that silver nanoparticles are capable of inhibiting arenavirus infection in vitro. The inhibition of viral replication must occur during early replication since although pre-infection treatment with silver nanoparticles is very effective, the post-infection addition of silver nanoparticles is only effective if administered within the first 2-4 hours of virus replication. CONCLUSIONS: Silver nanoparticles are capable of inhibiting a prototype arenavirus at non-toxic concentrations and effectively inhibit arenavirus replication when administered prior to viral infection or early after initial virus exposure. This suggests that the mode of action of viral neutralization by silver nanoparticles occurs during the early phases of viral replication.
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105Baram-Pinto, D.; Shukla, S.; Perkas, N.; Gedanken, A.; Sarid, R. Inhibition of Herpes Simplex Virus Type 1 Infection by Silver Nanoparticles Capped with Mercaptoethane Sulfonate. Bioconjugate Chem. 2009, 20, 1497– 1502, DOI: 10.1021/bc900215b105https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXot1Gnu78%253D&md5=c170aebd3c6b0924eee7a26b1a8746c8Inhibition of Herpes Simplex Virus Type 1 Infection by Silver Nanoparticles Capped with Mercaptoethane SulfonateBaram-Pinto, Dana; Shukla, Sourabh; Perkas, Nina; Gedanken, Aharon; Sarid, RonitBioconjugate Chemistry (2009), 20 (8), 1497-1502CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)Interactions between biomols. and nanoparticles suggest the use of nanoparticles for various medical interventions. The attachment and entry of herpes simplex virus type 1 (HSV-1) into cells involve interaction between viral envelope glycoproteins and cell surface heparan sulfate (HS). Based on this mechanism, we designed silver nanoparticles that are capped with mercaptoethane sulfonate (Ag-MES). These nanoparticles are predicted to target the virus and to compete for its binding to cellular HS through their sulfonate end groups, leading to the blockage of viral entry into the cell and to the prevention of subsequent infection. Structurally defined Ag-MES nanoparticles that are readily redispersible in water were sonochem. synthesized. No toxic effects of these nanoparticles on host cells were obsd. Effective inhibition of HSV-1 infection in cell culture by the capped nanoparticles was demonstrated. However, application of the sol. surfactant MES failed to inhibit viral infection, implying that the antiviral effect of Ag-MES nanoparticles is imparted by their multivalent nature and spatially directed MES on the surface. Our results suggest that capped nanoparticles may serve as useful topical agents for the prevention of infections with pathogens dependent on HS for entry.
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106Orłowski, P.; Kowalczyk, A.; Tomaszewska, E.; Ranoszek-Soliwoda, K.; Wȩgrzyn, A.; Grzesiak, J.; Celichowski, G.; Grobelny, J.; Eriksson, K.; Krzyzowska, M. Antiviral Activity of Tannic Acid Modified Silver Nanoparticles: Potential to Activate Immune Response in Herpes Genitalis. Viruses 2018, 10, 524, DOI: 10.3390/v10100524106https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXmvFGrs7Y%253D&md5=5f5438b29ec978984cc3c85ac343a8d1Antiviral activity of tannic acid modified silver nanoparticles: potential to activate immune response in herpes genitalisOrlowski, Piotr; Kowalczyk, Andrzej; Tomaszewska, Emilia; Ranoszek-Soliwoda, Katarzyna; W, egrzyn, Agnieszka; Grzesiak, Jakub; Celichowski, Grzegorz; Grobelny, Jaroslaw; Eriksson, Kristina; Krzyzowska, MalgorzataViruses (2018), 10 (10), 524/1-524/15CODEN: VIRUBR; ISSN:1999-4915. (MDPI AG)Tannic acid is a plant-derived polyphenol showing antiviral activity mainly because of an interference with the viral adsorption. In this work, we tested whether the modification of silver nanoparticles with tannic acid (TA-AgNPs) can provide a microbicide with addnl. adjuvant properties to treat genital herpes infection. The mouse model of the vaginal herpes simplex virus 2 (HSV-2) infection was used to test immune responses after treatment of the primary infection with TA-AgNPs, and later, after a re-challenge with the virus. The mice treated intravaginally with TA-AgNPs showed better clin. scores and lower virus titers in the vaginal tissues soon after treatment. Following a re-challenge, the vaginal tissues treated with TA-AgNPs showed a significant increase in the percentages of IFN-gamma+ CD8+ T-cells, activated B cells, and plasma cells, while the spleens contained significantly higher percentages of IFN-gamma+ NK cells and effector-memory CD8+ T cells in comparison to NaCl-treated group. TA-AgNPs-treated animals also showed significantly better titers of anti-HSV-2 neutralization antibodies in sera; and. Our findings suggest that TA-AgNPs sized 33 nm can be an effective anti-viral microbicide to be applied upon the mucosal tissues with addnl. adjuvant properties enhancing an anti-HSV-2 immune response following secondary challenge.
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107Gaikwad, S.; Ingle, A.; Gade, A.; Rai, M.; Falanga, A.; Incoronato, N.; Russo, L.; Galdiero, S.; Galdiero, M. Antiviral Activity of Mycosynthesized Silver Nanoparticles against Herpes Simplex Virus and Human Parainfluenza Virus Type 3. Int. J. Nanomed. 2013, 8, 4303– 4314, DOI: 10.2147/IJN.S50070There is no corresponding record for this reference.
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108Qin, T.; Ma, R.; Yin, Y.; Miao, X.; Chen, S.; Fan, K.; Xi, J.; Liu, Q.; Gu, Y.; Yin, Y.; Hu, J.; Liu, X.; Peng, D.; Gao, L. Catalytic Inactivation of Influenza Virus by Iron Oxide Nanozyme. Theranostics 2019, 9, 6920– 6935, DOI: 10.7150/thno.35826108https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXps1GjurY%253D&md5=c68a1e8e211cb41e8cf7f02b122d7ac8Catalytic inactivation of influenza virus by iron oxide nanozymeQin, Tao; Ma, Ruonan; Yin, Yinyan; Miao, Xinyu; Chen, Sujuan; Fan, Kelong; Xi, Juqun; Liu, Qi; Gu, Yunhao; Yin, Yuncong; Hu, Jiao; Liu, Xiufan; Peng, Daxin; Gao, LizengTheranostics (2019), 9 (23), 6920-6935CODEN: THERDS; ISSN:1838-7640. (Ivyspring International Publisher)Influenza poses a severe threat to human health in the world. However, developing a universal anti-viral strategy has remained challenging due to the presence of diverse subtypes as well as its high mutation rate, resulting in antigenic shift and drift. Here we developed an antiviral strategy using iron oxide nanozymes (IONzymes) to target the lipid envelope of the influenza virus. Methods: We evaluated the antiviral activities of our IONzymes using a hemagglutination assay, together with a 50% tissue culture infectious doses (TCID50) method. Lipid peroxidn. of the viral envelope was analyzed using a maleic dialdehyde (MDA) assay and transmission electron microscopy (TEM). The neighboring viral proteins were detected by western blotting. Results: We show that IONzymes induce envelope lipid peroxidn. and destroy the integrity of neighboring proteins, including hemagglutinin, neuraminidase, and matrix protein 1, causing the inactivation of influenza A viruses (IAVs). Furthermore, we show that our IONzymes possess a broad-spectrum antiviral activity on 12 subtypes of IAVs (H1~ H12). Lastly, we demonstrate that applying IONzymes to a facemask improves the ability of virus protection against 3 important subtypes that pose a threat to human, including H1N1, H5N1, and H7N9 subtype. Conclusion: Together, our results clearly demonstrate that IONzymes can catalyze lipid peroxidn. of the viral lipid envelope to inactivate enveloped viruses and provide protection from viral transmission and infection.
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109Lim, M. E.; Lee, Y. L.; Zhang, Y.; Chu, J. J. Photodynamic Inactivation of Viruses Using Upconversion Nanoparticles. Biomaterials 2012, 33, 1912– 1920, DOI: 10.1016/j.biomaterials.2011.11.033109https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhs1ejtLzI&md5=a1bff591872b481e1da97c1a0f5213e9Photodynamic inactivation of viruses using upconversion nanoparticlesLim, Meng Earn; Lee, Yen-ling; Zhang, Yong; Chu, Justin Jang HannBiomaterials (2012), 33 (6), 1912-1920CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)Photodynamic therapy (PDT) is a promising treatment modality that utilizes light of an appropriate wavelength to excite photosensitive materials called photosensitizers, which upon excitation, generate reactive oxygen species (ROS) that are cytocidal and virucidal. However, problems such as hydrophobicity of photosensitizers and limited tissue penetration ability of the current light sources impeded its promotion as a mainstay in medical technol. Here, by using near-IR (NIR)-to-visible upconversion nanoparticles (UCNs), we demonstrate UCN-based photodynamic inactivation as a potential antiviral strategy. These UCNs are nanotransducers which not only act as carriers of photosensitizers but also active participants in PDT by transducing NIR radiation to visible emissions appropriate for excitation of the attached photosensitizers. The UCNs effectively reduced the infectious virus titers in vitro with no clear pathogenicity in murine model and increased target specificity to virus-infected cells. Hence, this is a promising antiviral approach with feasible applications in the treatments of virus-assocd. infections, lesions and cancers.
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110Meléndez-Villanueva, M. A.; Morán-Santibañez, K.; Martínez-Sanmiguel, J. J.; Rangel-López, R.; Garza-Navarro, M. A.; Rodríguez-Padilla, C.; Zarate-Triviño, D. G.; Trejo-Ávila, L. M. Virucidal Activity of Gold Nanoparticles Synthesized by Green Chemistry Using Garlic Extract. Viruses 2019, 11, 1111, DOI: 10.3390/v11121111110https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXmsVGku7o%253D&md5=04385cea5d4f4f1e7245f3965af92c4aVirucidal activity of gold nanoparticles synthesized by green chemistry using garlic extractMelendez-Villanueva, Mayra A.; Moran-Santibanez, Karla; Martinez-Sanmiguel, Juan J.; Rangel-Lopez, Raul; Garza-Navarro, Marco A.; Rodriguez-Padilla, Cristina; Zarate-Trivino, Diana G.; Trejo-Avila, Laura M.Viruses (2019), 11 (12), 1111CODEN: VIRUBR; ISSN:1999-4915. (MDPI AG)Measles virus (MeV) is a paramyxovirus that infects humans, principally children. Despite the existence of an effective and safe vaccine, the no. of cases of measles has increased due to lack of vaccination coverage. The World Health Organization (WHO) reports that the no. of cases worldwide multiplied fourfold between Jan. and March 2019, to 112,000. Today, there is no treatment available for MeV. In recent years, it has been demonstrated that natural exts. (herbal or algal) with antiviral activity can also work as reducing agents that, in combination with nanotechnol., offer an innovative option to counteract viral infections. Here, we synthesized and evaluated the antiviral activity of gold nanoparticles using garlic ext. (Allium sativa) as a reducing agent (AuNPs-As). These nanoparticles actively inhibited MeV replication in Vero cells at a 50% effective concn. (EC50) of 8.829 μg/mL, and the selectivity index (SI) obtained was 16.05. AuNPs-As likely inhibit viral infection by blocking viral particles directly, showing a potent virucidal effect. Gold nanoparticles may be useful as a promising strategy for treating and controlling the infection of MeV and other related enveloped viruses.
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111Wang, Z.; Liu, H.; Yang, S. H.; Wang, T.; Liu, C.; Cao, Y. C. Nanoparticle-Based Artificial RNA Silencing Machinery for Antiviral Therapy. Proc. Natl. Acad. Sci. U. S. A. 2012, 109, 12387– 12392, DOI: 10.1073/pnas.1207766109111https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtleqsrjF&md5=486acf5ec619e96a368f1537796f5906Nanoparticle-based artificial RNA silencing machinery for antiviral therapyWang, Zhongliang; Liu, Hongyan; Yang, Soon Hye; Wang, Tie; Liu, Chen; Cao, Y. CharlesProceedings of the National Academy of Sciences of the United States of America (2012), 109 (31), 12387-12392, S12387/1-S12387/7CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)RNA interference is a fundamental gene regulatory mechanism that is mediated by the RNA-induced silencing complex (RISC). Here we report that an artificial nanoparticle complex can effectively mimic the function of the cellular RISC machinery for inducing target RNA cleavage. Our results show that a specifically designed nanozyme for the treatment of hepatitis C virus (HCV) can actively cleave HCV RNA in a sequence specific manner. This nanozyme is less susceptible to degrdn. by proteinase activity, can be effectively taken up by cultured human hepatoma cells, is nontoxic to the cultured cells and a xenotransplantation mouse model under the conditions studied, and does not trigger detectable cellular interferon response, but shows potent antiviral activity against HCV in cultured cells and in the mouse model. We have obsd. a more than 99% decrease in HCV RNA levels in mice treated with the nanozyme. These results show that this nanozyme approach has the potential to become a useful tool for functional genomics, as well as for combating protein-expression-related diseases such as viral infections and cancers.
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112Park, S.; Ko, Y. S.; Lee, S. J.; Lee, C.; Woo, K.; Ko, G. Inactivation of Influenza a Virus Via Exposure to Silver Nanoparticle-Decorated Silica Hybrid Composites. Environ. Sci. Pollut. Res. 2018, 25, 27021– 27030, DOI: 10.1007/s11356-018-2620-z112https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhtlGlsb%252FO&md5=54b7670a25dc289c763cd6e9848c692aInactivation of influenza A virus via exposure to silver nanoparticle-decorated silica hybrid compositesPark, SungJun; Ko, Young-Seon; Lee, Su Jin; Lee, Cheonghoon; Woo, Kyoungja; Ko, GwangPyoEnvironmental Science and Pollution Research (2018), 25 (27), 27021-27030CODEN: ESPLEC; ISSN:0944-1344. (Springer)Influenza A virus (IFV-A) is one of the main cause of seasonal flu and can infect various of host species via the reassortment of segmented RNA genomes. Silver nanoparticles (AgNPs) have been known as excellent antiviral agent against IFV. However, the use of free AgNPs has several major drawbacks, including the inherent aggregation among AgNPs and unwanted cytotoxic or genotoxic damages for human body via inhalation or ingestion. In this study, we assessed the efficacy of our novel ∼ 30-nm-diam. AgNP-decorated silica hybrid composite (Ag30-SiO2; ∼ 400 nm in diam.) for IFV-A inactivation. Ag30-SiO2 particles can inhibit IFV-A effectively in a clear dose-dependent manner. However, when real-time RT-PCR assay was used, merely 0.5-log10 redn. of IFV-A was obsd. at both 5 and 20°C. Moreover, even after 1 h of exposure to Ag30-SiO2 particles, more than 80% of hemagglutinin (HA) damage and 20% of neuraminidase (NA) activities had occurred, and the infection of Madin-Darby Canine Kidney (MDCK) cells by IFV-A was reduced. The results suggested that the major antiviral mechanism of Ag30-SiO2 particles is the interaction with viral components located at the membrane. Therefore, Ag30-SiO2 particles can cause nonspecific damage to various IFV-A components and be used as an effective method for inactivating IFV-A.
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113Botequim, D.; Maia, J.; Lino, M. M. F.; Lopes, L. M. F.; Simões, P. N.; Ilharco, L. M.; Ferreira, L. Nanoparticles and Surfaces Presenting Antifungal, Antibacterial and Antiviral Properties. Langmuir 2012, 28, 7646– 7656, DOI: 10.1021/la300948n113https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XmtlCrsrc%253D&md5=83f50bdd9b57eadc56e72a02f1698d21Nanoparticles and Surfaces Presenting Antifungal, Antibacterial and Antiviral PropertiesBotequim, D.; Maia, J.; Lino, M. M. F.; Lopes, L. M. F.; Simoes, P. N.; Ilharco, L. M.; Ferreira, L.Langmuir (2012), 28 (20), 7646-7656CODEN: LANGD5; ISSN:0743-7463. (American Chemical Society)Here, we present new antimicrobial nanoparticles based on silica nanoparticles (SNPs) coated with a quaternary ammonium cationic surfactant, didodecyldimethylammonium bromide (DDAB). Depending on the initial concn. of DDAB, SNPs immobilize between 45 and 275 μg of DDAB per mg of nanoparticle. For high concns. of DDAB adsorbed to SNP, a bilayer is formed as confirmed by zeta potential measurements, thermogravimetry, and diffuse reflectance IR Fourier transform (DRIFT) analyses. Interestingly, these nanoparticles have lower minimal inhibitory concns. (MIC) against bacteria and fungi than sol. surfactant. The electrostatic interaction of the DDAB with the SNP is strong, since no measurable loss of antimicrobial activity was obsd. after suspension in aq. soln. for 60 days. We further show that the antimicrobial activity of the nanoparticle does not require the leaching of the surfactant from the surface of the NPs. The SNPs may be immobilized onto surfaces with different chem. while maintaining their antimicrobial activity, in this case extended to a virucidal activity. The versatility, relative facility in prepn., low cost, and large antimicrobial activity of our platform makes it attractive as a coating for large surfaces.
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114Lara, H. H.; Ayala-Nuñez, N. V.; Ixtepan-Turrent, L.; Rodriguez-Padilla, C. Mode of Antiviral Action of Silver Nanoparticles against HIV-1. J. Nanobiotechnol. 2010, 8, 1, DOI: 10.1186/1477-3155-8-1114https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3c%252FpslertQ%253D%253D&md5=41c3f4b3c6c9d2bbe683745cc677830dMode of antiviral action of silver nanoparticles against HIV-1Lara Humberto H; Ayala-Nunez Nilda V; Ixtepan-Turrent Liliana; Rodriguez-Padilla CristinaJournal of nanobiotechnology (2010), 8 (), 1 ISSN:.BACKGROUND: Silver nanoparticles have proven to exert antiviral activity against HIV-1 at non-cytotoxic concentrations, but the mechanism underlying their HIV-inhibitory activity has not been not fully elucidated. In this study, silver nanoparticles are evaluated to elucidate their mode of antiviral action against HIV-1 using a panel of different in vitro assays. RESULTS: Our data suggest that silver nanoparticles exert anti-HIV activity at an early stage of viral replication, most likely as a virucidal agent or as an inhibitor of viral entry. Silver nanoparticles bind to gp120 in a manner that prevents CD4-dependent virion binding, fusion, and infectivity, acting as an effective virucidal agent against cell-free virus (laboratory strains, clinical isolates, T and M tropic strains, and resistant strains) and cell-associated virus. Besides, silver nanoparticles inhibit post-entry stages of the HIV-1 life cycle. CONCLUSIONS: These properties make them a broad-spectrum agent not prone to inducing resistance that could be used preventively against a wide variety of circulating HIV-1 strains.
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115Wei, X.; Zhang, G.; Ran, D.; Krishnan, N.; Fang, R. H.; Gao, W.; Spector, S. A.; Zhang, L. T-Cell-Mimicking Nanoparticles Can Neutralize HIV Infectivity. Adv. Mater. 2018, 30, 1802233, DOI: 10.1002/adma.201802233There is no corresponding record for this reference.
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116Bai, Y.; Zhou, Y.; Liu, H.; Fang, L.; Liang, J.; Xiao, S. Glutathione-Stabilized Fluorescent Gold Nanoclusters Vary in Their Influences on the Proliferation of Pseudorabies Virus and Porcine Reproductive and Respiratory Syndrome Virus. ACS Appl. Nano Mater. 2018, 1, 969– 976, DOI: 10.1021/acsanm.7b00386116https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhsl2jsbs%253D&md5=64430c2280999058678ccf45c71c6660Glutathione-Stabilized Fluorescent Gold Nanoclusters Vary in Their Influences on the Proliferation of Pseudorabies Virus and Porcine Reproductive and Respiratory Syndrome VirusBai, Yanli; Zhou, Yanrong; Liu, Huabing; Fang, Liurong; Liang, Jiangong; Xiao, ShaoboACS Applied Nano Materials (2018), 1 (2), 969-976CODEN: AANMF6; ISSN:2574-0970. (American Chemical Society)Gold nanoclusters (Au NCs) are widely used in biol. imaging and antitumor treatment because of their excellent cell membrane permeability, good fluorescence properties, and high biocompatibility. However, their effects on viruses are still largely unknown. Here, pseudorabies virus (PRV) and porcine reproductive and respiratory syndrome virus (PRRSV) were used resp. as the models of DNA virus and RNA virus to investigate the influences of glutathione-stabilized fluorescent Au NCs on viruses by plaque assay, indirect immunofluorescence assay, quant. real-time polymerase chain reaction assay, and Western blot assay. The exptl. data indicated that Au NCs selectively inhibited proliferation and protein expression of PRRSV but not that of PRV. Mechanistically, Au NCs directly inactivated PRRSV and blocked viral adsorption but showed no effect on viral genome replication. These findings prompt the possibility of developing Au NCs as an effective specific antiviral nanomaterial against RNA virus infection in the future.
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117Zhang, J.-M.; An, J. Cytokines, Inflammation, and Pain. Int. Anesthesiol. Clin. 2007, 45, 27– 37, DOI: 10.1097/AIA.0b013e318034194e117https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD2s3msF2ltg%253D%253D&md5=24aae56f3283e4a330226c914fd846bcCytokines, inflammation, and painZhang Jun-Ming; An JianxiongInternational anesthesiology clinics (2007), 45 (2), 27-37 ISSN:0020-5907.There is no expanded citation for this reference.
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118Lung, P.; Yang, J.; Li, Q. Nanoparticle Formulated Vaccines: Opportunities and Challenges. Nanoscale 2020, 12, 5746– 5763, DOI: 10.1039/C9NR08958F118https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXktFWgsbw%253D&md5=65a2fc077008f9fa9d0ac85352a50c29Nanoparticle formulated vaccines: opportunities and challengesLung, Pingsai; Yang, Jingnan; Li, QuanNanoscale (2020), 12 (10), 5746-5763CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)Vaccines harness the inherent properties of the immune system to prevent diseases or treat existing ones. Continuous efforts have been devoted to both gaining a mechanistic understanding of how the immune system operates and designing vaccines with high efficacies and effectiveness. Advancements in nanotechnol. in recent years have generated unique opportunities to meet the daunting challenges assocd. with immunol. and vaccine development. Firstly, nanoparticle formulated systems provide ideal model systems for studying the operation of the immune system, making it possible to systematically identify key factors and understand their roles in specific immune responses. Also, the versatile compns./architectures of nanoparticle systems enable new strategies/novel platforms for developing vaccines with high efficacies and effectiveness. In this review, we discuss the advantages of nanoparticles and the challenges faced during vaccine development, through the framework of the immunol. mechanisms of vaccination, with the aim of bridging the gap between immunol. and materials science, which are both involved in vaccine design. The knowledge obtained provides general guidelines for future vaccine development.
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119Ramshaw, I. A.; Ramsay, A. J.; Karupiah, G.; Rolph, M. S.; Mahalingam, S.; Ruby, J. C. Cytokines and Immunity to Viral Infections. Immunol. Rev. 1997, 159, 119– 135, DOI: 10.1111/j.1600-065X.1997.tb01011.x119https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXnvFKrtLw%253D&md5=b03bef37289586a5a4a899b20b216157Cytokines and immunity to viral infectionsRamshaw, Ian A.; Ramsay, Alistair J.; Karupiah, Gunasegaran; Rolph, Michael S.; Mahalingam, Surendran; Ruby, Janet C.Immunological Reviews (1997), 159 (), 119-135CODEN: IMRED2; ISSN:0105-2896. (Munksgaard International Publishers Ltd.)In this review with 96 refs., the authors discuss 2 broad approaches they have taken to study the role of cytokines and chemokines in antiviral immunity. Firstly, recombinant vaccinia viruses were engineered to express genes encoding cytokines and chemokines of interest. Potent antiviral activity was mediated by many of these encoded factors, including IL-2, IL-12, IFN-γ, TNF-α, CD40L, Mig, and Crg-2. In some cases, host defense mechanisms were induced, while for others, a direct antiviral effect was demonstrated. In sharp contrast, vector-directed expression of IL-4, a type 2 factor, greatly increased virus virulence, due to a downregulation of host type 1 immune responses. The second exptl. approach involved the use of strains of mice deficient for the prodn. of particular cytokines or their receptors, often in combination with the authors' engineered viruses. Mice deficient in either IFN-γ, IFN-γR, IFN-α/βR, TNFRs, CD40, or IL-6 were, in general, highly susceptible to poxvirus infection. Surprisingly, not only the TNFR1, but also the TNFR2, mediated the antiviral effects of TNF-α in vivo, while the antiviral activity obsd. following CD40/CD40L interaction is a newly defined function which may involve apoptosis of infected cells. Through the use of perforin-deficient mice, the authors could demonstrate a requirement for this mol. in the clearance of some viruses, while for others perforin was less important but IFN-γ was essential.
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120Ruby, J.; Bluethmann, H.; Peschon, J. J. Antiviral Activity of Tumor Necrosis Factor (TNF) Is Mediated Via P55 and P75 TNF Receptors. J. Exp. Med. 1997, 186, 1591– 1596, DOI: 10.1084/jem.186.9.1591120https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXntFerurw%253D&md5=fe4957c7083a12ac69aaa5ba5ad58c09Antiviral activity of tumor necrosis factor (TNF) is mediated via p55 and p75 TNF receptorsRuby, Janet; Bluethmann, Horst; Peschon, Jacques J.Journal of Experimental Medicine (1997), 186 (9), 1591-1596CODEN: JEMEAV; ISSN:0022-1007. (Rockefeller University Press)The antiviral nature of tumor necrosis factor (TNF) is generally well accepted. TNF appears to induce multiple antiviral mechanisms, and to synergize with interferon (IFN)-γ in promoting antiviral activities. We infected TNF receptor (TNFR)-deficient mice with the virulent murine pathogen, ectromelia virus (EV), and obsd. that otherwise resistant mice were susceptible to lethal infection. To study the mol. basis of the antiviral action of TNF, mice were infected with a recombinant vaccinia virus encoding murine TNF (VV-HA-TNF). In normal mice, the replication of VV-HA-TNF was highly attenuated. In contrast, mice in which the TNFR type 1 (p55) or the TNFR type 2 (p75) were genetically disrupted showed a moderate defect in their capacity to clear the TNF-encoding virus. The contribution of both TNF receptors to the control of VV-HA-TNF was confirmed by the enhanced replication of VV-HA-TNF in mice deficient for both p55 and p75. These observations were corroborated by infecting TNFR-deficient mice with EV. For both infections, the p55 and p75 TNFRs were necessary to maintain normal levels of resistance. Thus, the antiviral activity of TNF is mediated via both TNFRs in vivo. Furthermore, these studies establish that TNF is an important component of the host response to a natural virus infection.
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121Sekimukai, H.; Iwata-Yoshikawa, N.; Fukushi, S.; Tani, H.; Kataoka, M.; Suzuki, T.; Hasegawa, H.; Niikura, K.; Arai, K.; Nagata, N. Gold Nanoparticle-Adjuvanted S Protein Induces a Strong Antigen-Specific IgG Response against Severe Acute Respiratory Syndrome-Related Coronavirus Infection, but Fails to Induce Protective Antibodies and Limit Eosinophilic Infiltration in Lungs. Microbiol. Immunol. 2020, 64, 33– 51, DOI: 10.1111/1348-0421.12754121https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXitFKhsrvJ&md5=bab1fc4834c5732cb199c12a925b1ecaGold nanoparticle-adjuvanted S protein induces a strong antigen-specific IgG response against severe acute respiratory syndrome-related coronavirus infection, but fails to induce protective antibodies and limit eosinophilic infiltration in lungsSekimukai, Hanako; Iwata-Yoshikawa, Naoko; Fukushi, Shuetsu; Tani, Hideki; Kataoka, Michiyo; Suzuki, Tadaki; Hasegawa, Hideki; Niikura, Kenichi; Arai, Katsuhiko; Nagata, NoriyoMicrobiology and Immunology (2020), 64 (1), 33-51CODEN: MIIMDV; ISSN:0385-5600. (Wiley-Blackwell)The spike (S) protein of coronavirus, which binds to cellular receptors and mediates membrane fusion for cell entry, is a candidate vaccine target for blocking coronavirus infection. However, some animal studies have suggested that inadequate immunization against severe acute respiratory syndrome coronavirus (SARS-CoV) induces a lung eosinophilic immunopathol. upon infection. The present study evaluated two kinds of vaccine adjuvants for use with recombinant S protein: gold nanoparticles (AuNPs), which are expected to function as both an antigen carrier and an adjuvant in immunization; and Toll-like receptor (TLR) agonists, which have previously been shown to be an effective adjuvant in an UV-inactivated SARS-CoV vaccine. All the mice immunized with more than 0.5μg S protein without adjuvant escaped from SARS after infection with mouse-adapted SARS-CoV; however, eosinophilic infiltrations were obsd. in the lungs of almost all the immunized mice. The AuNP-adjuvanted protein induced a strong IgG response but failed to improve vaccine efficacy or to reduce eosinophilic infiltration because of highly allergic inflammatory responses. Whereas similar virus titers were obsd. in the control animals and the animals immunized with S protein with or without AuNPs, Type 1 interferon and pro-inflammatory responses were moderate in the mice treated with S protein with and without AuNPs. On the other hand, the TLR agonist-adjuvanted vaccine induced highly protective antibodies without eosinophilic infiltrations, as well as Th1/17 cytokine responses. The findings of this study will support the development of vaccines against severe pneumonia-assocd. coronaviruses.
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122Chen, H.-W.; Huang, C.-Y.; Lin, S.-Y.; Fang, Z.-S.; Hsu, C.-H.; Lin, J.-C.; Chen, Y.-I.; Yao, B.-Y.; Hu, C. -M. J. Synthetic Virus-Like Particles Prepared Via Protein Corona Formation Enable Effective Vaccination in an Avian Model of Coronavirus Infection. Biomaterials 2016, 106, 111– 118, DOI: 10.1016/j.biomaterials.2016.08.018122https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtlCqsLvN&md5=08e077389dab6a2808eb43fd4939f703Synthetic virus-like particles prepared via protein corona formation enable effective vaccination in an avian model of coronavirus infectionChen, Hui-Wen; Huang, Chen-Yu; Lin, Shu-Yi; Fang, Zih-Syun; Hsu, Chen-Hsuan; Lin, Jung-Chen; Chen, Yuan-I.; Yao, Bing-Yu; Hu, Che-Ming J.Biomaterials (2016), 106 (), 111-118CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)The ongoing battle against current and rising viral infectious threats has prompted increasing effort in the development of vaccine technol. A major thrust in vaccine research focuses on developing formulations with virus-like features towards enhancing antigen presentation and immune processing. Herein, a facile approach to formulate synthetic virus-like particles (sVLPs) is demonstrated by exploiting the phenomenon of protein corona formation induced by the high-energy surfaces of synthetic nanoparticles. Using an avian coronavirus spike protein as a model antigen, sVLPs were prepd. by incubating 100 nm gold nanoparticles in a soln. contg. an optimized concn. of viral proteins. Following removal of free proteins, antigen-laden particles were recovered and showed morphol. semblance to natural viral particles under nanoparticle tracking anal. and transmission electron microscopy. As compared to inoculation with free proteins, vaccination with the sVLPs showed enhanced lymphatic antigen delivery, stronger antibody titers, increased splenic T-cell response, and reduced infection-assocd. symptoms in an avian model of coronavirus infection. Comparison to a com. whole inactivated virus vaccine also showed evidence of superior antiviral protection by the sVLPs. The study demonstrates a simple yet robust method in bridging viral antigens with synthetic nanoparticles for improved vaccine application; it has practical implications in the management of human viral infections as well as in animal agriculture.
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123Coleman, C. M.; Venkataraman, T.; Liu, Y. V.; Glenn, G. M.; Smith, G. E.; Flyer, D. C.; Frieman, M. B. MERS-CoV Spike Nanoparticles Protect Mice from MERS-CoV Infection. Vaccine 2017, 35, 1586– 1589, DOI: 10.1016/j.vaccine.2017.02.012123https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXjt1KmtLY%253D&md5=92ba1c44d18a8f0fa8f27c84b03392a8MERS-CoV spike nanoparticles protect mice from MERS-CoV infectionColeman, Christopher M.; Venkataraman, Thiagarajan; Liu, Ye V.; Glenn, Gregory M.; Smith, Gale E.; Flyer, David C.; Frieman, Matthew B.Vaccine (2017), 35 (12), 1586-1589CODEN: VACCDE; ISSN:0264-410X. (Elsevier Ltd.)The Middle East respiratory syndrome coronavirus (MERS-CoV) was first discovered in late 2012 and has gone on to cause over 1800 infections and 650 deaths. There are currently no approved therapeutics or vaccinations for MERS-CoV. The MERS-CoV spike (S) protein is responsible for receptor binding and virion entry to cells, is immunodominant and induces neutralizing antibodies in vivo, all of which, make the S protein an ideal target for anti-MERS-CoV vaccines. In this study, we demonstrate protection induced by vaccination with a recombinant MERS-CoV S nanoparticle vaccine and Matrix-M1 adjuvant combination in mice. The MERS-CoV S nanoparticle vaccine produced high titer anti-S neutralizing antibody and protected mice from MERS-CoV infection in vivo.
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124Pimentel, T. A. P. F.; Yan, Z.; Jeffers, S. A.; Holmes, K. V.; Hodges, R. S.; Burkhard, P. Peptide Nanoparticles as Novel Immunogens: Design and Analysis of a Prototypic Severe Acute Respiratory Syndrome Vaccine. Chem. Biol. Drug Des. 2009, 73, 53– 61, DOI: 10.1111/j.1747-0285.2008.00746.x124https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXptFCnsw%253D%253D&md5=0e37d95d999b6eb71b22f0af593c8a13Peptide nanoparticles as novel immunogens: design and analysis of a prototypic severe acute respiratory syndrome vaccinePimentel, Tais A. P. F.; Yan, Zhe; Jeffers, Scott A.; Holmes, Kathryn V.; Hodges, Robert S.; Burkhard, PeterChemical Biology & Drug Design (2009), 73 (1), 53-61CODEN: CBDDAL; ISSN:1747-0277. (Wiley-Blackwell)Severe acute respiratory syndrome (SARS) is an infectious disease caused by a novel coronavirus that cost nearly 800 lives. While there have been no recent outbreaks of the disease, the threat remains as SARS coronavirus (SARS-CoV) like strains still exist in animal reservoirs. Therefore, the development of a vaccine against SARS is in grave need. Here, the authors have designed and produced a prototypic SARS vaccine: a self-assembling polypeptide nanoparticle that repetitively displays a SARS B-cell epitope from the C-terminal heptad repeat of the virus' spike protein. Biophys. analyses with CD, TEM and dynamic light scattering confirmed the computational design showing α-helcial nanoparticles with sizes of about 25 nm. Immunization expts. with no adjuvants were performed with BALB/c mice. An investigation of the binding properties of the elicited antibodies showed that they were highly conformation specific for the coiled-coil epitope because they specifically recognized the native trimeric conformation of C-terminal heptad repeat region. Consequently, the antisera exhibited neutralization activity in an in vitro infection inhibition assay. The authors conclude that these peptide nanoparticles represent a promising platform for vaccine design, in particular for diseases that are characterized by neutralizing epitopes with coiled-coil conformation such as SARS-CoV or other enveloped viruses.
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125Wang, C.; Zheng, X.; Gai, W.; Wong, G.; Wang, H.; Jin, H.; Feng, N.; Zhao, Y.; Zhang, W.; Li, N.; Zhao, G.; Li, J.; Yan, J.; Gao, Y.; Hu, G.; Yang, S.; Xia, X. Novel Chimeric Virus-Like Particles Vaccine Displaying MERS-CoV Receptor-Binding Domain Induce Specific Humoral and Cellular Immune Response in Mice. Antiviral Res. 2017, 140, 55– 61, DOI: 10.1016/j.antiviral.2016.12.019125https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhsVelsrw%253D&md5=05f1fe4c2e3ee67be7659c56aa490f0fNovel chimeric virus-like particles vaccine displaying MERS-CoV receptor-binding domain induce specific humoral and cellular immune response in miceWang, Chong; Zheng, Xuexing; Gai, Weiwei; Wong, Gary; Wang, Hualei; Jin, Hongli; Feng, Na; Zhao, Yongkun; Zhang, Weijiao; Li, Nan; Zhao, Guoxing; Li, Junfu; Yan, Jinghua; Gao, Yuwei; Hu, Guixue; Yang, Songtao; Xia, XianzhuAntiviral Research (2017), 140 (), 55-61CODEN: ARSRDR; ISSN:0166-3542. (Elsevier B.V.)Middle East respiratory syndrome coronavirus (MERS-CoV) has continued spreading since its emergence in 2012 with a mortality rate of 35.6%, and is a potential pandemic threat. Prophylactics and therapies are urgently needed to address this public health problem. We report here the efficacy of a vaccine consisting of chimeric virus-like particles (VLP) expressing the receptor binding domain (RBD) of MERS-CoV. In this study, a fusion of the canine parvovirus (CPV) VP2 structural protein gene with the RBD of MERS-CoV can self-assemble into chimeric, spherical VLP (sVLP). SVLP retained certain parvovirus characteristics, such as the ability to agglutinate pig erythrocytes, and structural morphol. similar to CPV virions. Immunization with sVLP induced RBD-specific humoral and cellular immune responses in mice. SVLP-specific antisera from these animals were able to prevent pseudotyped MERS-CoV entry into susceptible cells, with neutralizing antibody titers reaching 1:320. IFN-γ, IL-4 and IL-2 secreting cells induced by the RBD were detected in the splenocytes of vaccinated mice by ELISpot. Furthermore, mice inoculated with sVLP or an adjuvanted sVLP vaccine elicited T-helper 1 (Th1) and T-helper 2 (Th2) cell-mediated immunity. Our study demonstrates that sVLP displaying the RBD of MERS-CoV are promising prophylactic candidates against MERS-CoV in a potential outbreak situation.
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126Wiley, J. A.; Richert, L. E.; Swain, S. D.; Harmsen, A.; Barnard, D. L.; Randall, T. D.; Jutila, M.; Douglas, T.; Broomell, C.; Young, M.; Harmsen, A. Inducible Bronchus-Associated Lymphoid Tissue Elicited by a Protein Cage Nanoparticle Enhances Protection in Mice against Diverse Respiratory Viruses. PLoS One 2009, 4, e7142, DOI: 10.1371/journal.pone.0007142There is no corresponding record for this reference.
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127Lin, L. C. -W.; Huang, C.-Y.; Yao, B.-Y.; Lin, J.-C.; Agrawal, A.; Algaissi, A.; Peng, B.-H.; Liu, Y.-H.; Huang, P.-H.; Juang, R.-H.; Chang, Y.-C.; Tseng, C.-T.; Chen, H.-W.; Hu, C. -M. J. Viromimetic Sting Agonist-Loaded Hollow Polymeric Nanoparticles for Safe and Effective Vaccination against Middle East Respiratory Syndrome Coronavirus. Adv. Funct. Mater. 2019, 29, 1807616, DOI: 10.1002/adfm.201807616127https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB38znsFWmsw%253D%253D&md5=08ea75b08135b931abb937b01c2dddc5Viromimetic STING Agonist-Loaded Hollow Polymeric Nanoparticles for Safe and Effective Vaccination against Middle East Respiratory Syndrome CoronavirusLin Leon Chien-Wei; Yao Bing-Yu; Lin Jung-Chen; Liu Yu-Han; Hu Che-Ming Jack; Huang Chen-Yu; Huang Ping-Han; Chen Hui-Wen; Agrawal Anurodh; Algaissi Abdullah; Tseng Chien-Te; Algaissi Abdullah; Peng Bi-Hung; Juang Rong-Huay; Chang Yuan-Chih; Tseng Chien-TeAdvanced functional materials (2019), 29 (28), 1807616 ISSN:1616-301X.The continued threat of emerging, highly lethal infectious pathogens such as Middle East respiratory syndrome coronavirus (MERS-CoV) calls for the development of novel vaccine technology that offers safe and effective prophylactic measures. Here, a novel nanoparticle vaccine is developed to deliver subunit viral antigens and STING agonists in a virus-like fashion. STING agonists are first encapsulated into capsid-like hollow polymeric nanoparticles, which show multiple favorable attributes, including a pH-responsive release profile, prominent local immune activation, and reduced systemic reactogenicity. Upon subsequent antigen conjugation, the nanoparticles carry morphological semblance to native virions and facilitate codelivery of antigens and STING agonists to draining lymph nodes and immune cells for immune potentiation. Nanoparticle vaccine effectiveness is supported by the elicitation of potent neutralization antibody and antigen-specific T cell responses in mice immunized with a MERS-CoV nanoparticle vaccine candidate. Using a MERS-CoV-permissive transgenic mouse model, it is shown that mice immunized with this nanoparticle-based MERS-CoV vaccine are protected against a lethal challenge of MERS-CoV without triggering undesirable eosinophilic immunopathology. Together, the biocompatible hollow nanoparticle described herein provides an excellent strategy for delivering both subunit vaccine candidates and novel adjuvants, enabling accelerated development of effective and safe vaccines against emerging viral pathogens.
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128Plummer, E. M.; Manchester, M. Viral Nanoparticles and Virus-Like Particles: Platforms for Contemporary Vaccine Design. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 2011, 3, 174– 196, DOI: 10.1002/wnan.119128https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXislCkur8%253D&md5=3afbaf5a8765a7d8ebb05aac7982d5eeViral nanoparticles and virus-like particles: platforms for contemporary vaccine designPlummer, Emily M.; Manchester, MarianneWiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology (2011), 3 (2), 174-196CODEN: WIRNBH; ISSN:1939-0041. (Wiley-Blackwell)A review. Current vaccines that provide protection against infectious diseases have primarily relied on attenuated or inactivated pathogens. Virus-like particles (VLPs), comprised of capsid proteins that can initiate an immune response but do not include the genetic material required for replication, promote immunogenicity and have been developed and approved as vaccines in some cases. In addn., many of these VLPs can be used as mol. platforms for genetic fusion or chem. attachment of heterologous antigenic epitopes. This approach has been shown to provide protective immunity against the foreign epitopes in many cases. A variety of VLPs and virus-based nanoparticles are being developed for use as vaccines and epitope platforms. These particles have the potential to increase efficacy of current vaccines as well as treat diseases for which no effective vaccines are available.
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129Peek, L. J.; Middaugh, C. R.; Berkland, C. Nanotechnology in Vaccine Delivery. Adv. Drug Delivery Rev. 2008, 60, 915– 928, DOI: 10.1016/j.addr.2007.05.017129https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXlslagu7Y%253D&md5=ab9915070bea91ba6b236b11f0d37a68Nanotechnology in vaccine deliveryPeek, Laura J.; Middaugh, C. Russell; Berkland, CoryAdvanced Drug Delivery Reviews (2008), 60 (8), 915-928CODEN: ADDREP; ISSN:0169-409X. (Elsevier B.V.)A review. With very few adjuvants currently being used in marketed human vaccines, a crit. need exists for novel immunopotentiators and delivery vehicles capable of eliciting humoral, cellular and mucosal immunity. Such crucial vaccine components could facilitate the development of novel vaccines for viral and parasitic infections, such as hepatitis, HIV, malaria, cancer, etc. In this review, we discuss clin. trial results for various vaccine adjuvants and delivery vehicles being developed that are approx. nanoscale (< 1000 nm) in size. Humoral immune responses have been obsd. for most adjuvants and delivery platforms while only viral vectors, ISCOMs and Montanide ISA 51 and 720 have shown cytotoxic T cell responses in the clinic. MF59 and MPL have elicited Th1 responses, and virus-like particles, non-degradable nanoparticles and liposomes have also generated cellular immunity. Such vaccine components have also been evaluated for alternative routes of administration with clin. successes reported for intranasal delivery of viral vectors and proteosomes and oral delivery of a VLP vaccine.
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130World Health Organization (WHO). Draft Landscape of COVID-19 Candidate Vaccines, 2020. https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines (accessed Jul 10, 2020).There is no corresponding record for this reference.
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131Kim, Y.-S.; Son, A.; Kim, J.; Kwon, S. B.; Kim, M. H.; Kim, P.; Kim, J.; Byun, Y. H.; Sung, J.; Lee, J.; Yu, J. E.; Park, C.; Kim, Y.-S.; Cho, N.-H.; Chang, J.; Seong, B. L. Chaperna-Mediated Assembly of Ferritin-Based Middle East Respiratory Syndrome-Coronavirus Nanoparticles. Front. Immunol. 2018, 9, 1093, DOI: 10.3389/fimmu.2018.01093131https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXit1GjsrrE&md5=06d954421c57cd1fbe0b76793b71ebf2Chaperna-mediated assembly of ferritin-based middle east respiratory syndrome-coronavirus nanoparticlesKim, Young-Seok; Son, Ahyun; Kim, Jihoon; Kwon, Soon Bin; Kim, Myung Hee; Kim, Paul; Kim, Jieun; Byun, Young Ho; Sung, Jemin; Lee, Jinhee; Yu, Ji Eun; Park, Chan; Kim, Yeon-Sook; Cho, Nam-Hyuk; Chang, Jun; Seong, Baik L.Frontiers in Immunology (2018), 9 (), 1093/1-1093/20CODEN: FIRMCW; ISSN:1664-3224. (Frontiers Media S.A.)The folding of monomeric antigens and their subsequent assembly into higher ordered structures are crucial for robust and effective prodn. of nanoparticle (NP) vaccines in a timely and reproducible manner. Despite significant advances in in silico design and structure-based assembly, most engineered NPs are refractory to sol. expression and fail to assemble as designed, presenting major challenges in the manufg. process. The failure is due to a lack of understanding of the kinetic pathways and enabling tech. platforms to ensure successful folding of the monomer antigens into regular assemblages. Capitalizing on a novel function of RNA as a mol. chaperone (chaperna: chaperone + RNA), we provide a robust protein-folding vehicle that may be implemented to NP assembly in bacterial hosts. The receptor-binding domain (RBD) of Middle East respiratory syndrome-coronavirus (MERS-CoV) was fused with the RNA-interaction domain (RID) and bacterioferritin, and expressed in Escherichia coli in a sol. form. Site-specific proteolytic removal of the RID prompted the assemblage of monomers into NPs, which was confirmed by electron microscopy and dynamic light scattering. The mutations that affected the RNA binding to RBD significantly increased the sol. aggregation into amorphous structures, reducing the overall yield of NPs of a defined size. This underscored the RNA-antigen interactions during NP assembly. The sera after mouse immunization effectively interfered with the binding of MERS-CoV RBD to the cellular receptor hDPP4. The results suggest that RNA-binding controls the overall kinetic network of the antigen folding pathway in favor of enhanced assemblage of NPs into highly regular and immunol. relevant conformations. The concn. of the ion Fe2+, salt, and fusion linker also contributed to the assembly in vitro, and the stability of the NPs. The kinetic "pace-keeping" role of chaperna in the super mol. assembly of antigen monomers holds promise for the development and delivery of NPs and virus-like particles as recombinant vaccines and for serol. detection of viral infections.
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132Carter, D. C.; Wright, B.; Jerome, W. G.; Rose, J. P.; Wilson, E. A Unique Protein Self-Assembling Nanoparticle with Significant Advantages in Vaccine Development and Production. J. Nanomater. 2020, 2020, 4297937, DOI: 10.1155/2020/4297937There is no corresponding record for this reference.
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133Gelperina, S.; Kisich, K.; Iseman, M. D.; Heifets, L. The Potential Advantages of Nanoparticle Drug Delivery Systems in Chemotherapy of Tuberculosis. Am. J. Respir. Crit. Care Med. 2005, 172, 1487– 1490, DOI: 10.1164/rccm.200504-613PP133https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD2MnlsFeiuw%253D%253D&md5=3cd1441a228062dc8c82e3501b068e49The potential advantages of nanoparticle drug delivery systems in chemotherapy of tuberculosisGelperina Svetlana; Kisich Kevin; Iseman Michael D; Heifets LeonidAmerican journal of respiratory and critical care medicine (2005), 172 (12), 1487-90 ISSN:1073-449X.Nanoparticle-based drug delivery systems have considerable potential for treatment of tuberculosis (TB). The important technological advantages of nanoparticles used as drug carriers are high stability, high carrier capacity, feasibility of incorporation of both hydrophilic and hydrophobic substances, and feasibility of variable routes of administration, including oral application and inhalation. Nanoparticles can also be designed to allow controlled (sustained) drug release from the matrix. These properties of nanoparticles enable improvement of drug bioavailability and reduction of the dosing frequency, and may resolve the problem of nonadherence to prescribed therapy, which is one of the major obstacles in the control of TB epidemics. This article highlights some of the issues of nanotechnology relevant to the anti-TB drugs.
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134Singh, R.; Lillard, J. W. Nanoparticle-Based Targeted Drug Delivery. Exp. Mol. Pathol. 2009, 86, 215– 223, DOI: 10.1016/j.yexmp.2008.12.004134https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXlslWhtrs%253D&md5=51bbe150de7e5f9db5c27a9717198dffNanoparticle-based targeted drug deliverySingh, Rajesh; Lillard, James W.Experimental and Molecular Pathology (2009), 86 (3), 215-223CODEN: EXMPA6; ISSN:0014-4800. (Elsevier B.V.)A review. Nanotechnol. could be defined as the technol. that has allowed for the control, manipulation, study, and manuf. of structures and devices in the "nanometer" size range. These nano-sized objects, e.g., "nanoparticles", take on novel properties and functions that differ markedly from those seen from items made of identical materials. The small size, customized surface, improved soly., and multi-functionality of nanoparticles will continue to open many doors and create new biomedical applications. Indeed, the novel properties of nanoparticles offer the ability to interact with complex cellular functions in new ways. This rapidly growing field requires cross-disciplinary research and provides opportunities to design and develop multifunctional devices that can target, diagnose, and treat devastating diseases such as cancer. This article presents an overview of nanotechnol. for the biologist and discusses the attributes of the authors' novel XPclad nanoparticle formulation that has shown efficacy in treating solid tumors, single dose vaccination, and oral delivery of therapeutic proteins.
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135Sung, J. C.; Pulliam, B. L.; Edwards, D. A. Nanoparticles for Drug Delivery to the Lungs. Trends Biotechnol. 2007, 25, 563– 570, DOI: 10.1016/j.tibtech.2007.09.005135https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhtlCru7nK&md5=9a83415324703aa9cf44720616b4fff4Nanoparticles for drug delivery to the lungsSung, Jean C.; Pulliam, Brian L.; Edwards, David A.Trends in Biotechnology (2007), 25 (12), 563-570CODEN: TRBIDM; ISSN:0167-7799. (Elsevier B.V.)A review. The lungs are an attractive route for non-invasive drug delivery with advantages for both systemic and local applications. Incorporating therapeutics with polymeric nanoparticles offers addnl. degrees of manipulation for delivery systems, providing sustained release and the ability to target specific cells and organs. However, nanoparticle delivery to the lungs has many challenges including formulation instability due to particle-particle interactions and poor delivery efficiency due to exhalation of low-inertia nanoparticles. Thus, novel methods formulating nanoparticles into the form of micron-scale dry powders were developed. These carrier particles exhibit improved handling and delivery, while releasing nanoparticles upon deposition in the lungs. This review covers the development of nanoparticle formulations for pulmonary delivery as both individual nanoparticles and encapsulated within carrier particles.
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136Arruebo, M.; Fernández-Pacheco, R.; Ibarra, M. R.; Santamaría, J. Magnetic Nanoparticles for Drug Delivery. Nano Today 2007, 2, 22– 32, DOI: 10.1016/S1748-0132(07)70084-1There is no corresponding record for this reference.
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137Bryan, W. W.; Medhi, R.; Marquez, M. D.; Rittikulsittichai, S.; Tran, M.; Lee, T. R. Porous Silver-Coated pNIPAM-Co-AAc Hydrogel Nanocapsules. Beilstein J. Nanotechnol. 2019, 10, 1973– 1982, DOI: 10.3762/bjnano.10.194137https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXitlShsb3K&md5=dcfc82e7827e3ec8238b2cc979f958e9Porous silver-coated pNIPAM-co-AAc hydrogel nanocapsulesBryan, William W.; Medhi, Riddhiman; Marquez, Maria D.; Rittikulsittichai, Supparesk; Tran, Michael; Lee, T. RandallBeilstein Journal of Nanotechnology (2019), 10 (), 1973-1982CODEN: BJNEAH; ISSN:2190-4286. (Beilstein-Institut zur Foerderung der Chemischen Wissenschaften)This paper describes the prepn. and characterization of a new type of core-shell nanoparticle in which the structure consists of a hydrogel core encapsulated within a porous silver shell. The thermo-responsive hydrogel cores were prepd. by surfactant-free emulsion polymn. of a selected mixt. of N-isopropylacrylamide (NIPAM) and acrylic acid (AAc). The hydrogel cores were then encased within either a porous or complete silver shell for which the localized surface plasmon resonance (LSPR) extends from visible to near-IR (NIR) wavelengths (i.e., max varies from 550 to 1050 nm, depending on the porosity), allowing for reversible contraction and swelling of the hydrogel via photothermal heating of the surrounding silver shell. Given that NIR light can pass through tissue, and the silver shell is porous, this system can serve as a platform for the smart delivery of payloads stored within the hydrogel core. The morphol. and compn. of the composite nanoparticles were characterized by SEM, TEM, and FTIR, resp. UV-vis spectroscopy was used to characterize the optical properties.
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138Tacken, P. J.; de Vries, I. J. M.; Torensma, R.; Figdor, C. G. Dendritic-Cell Immunotherapy: From Ex Vivo Loading to In Vivo Targeting. Nat. Rev. Immunol. 2007, 7, 790– 802, DOI: 10.1038/nri2173138https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhtVOrtbjL&md5=b462fa900c109e377467d4a2f37a20e4Dendritic-cell immunotherapy: from ex vivo loading to in vivo targetingTacken, Paul J.; de Vries, I. Jolanda M.; Torensma, Ruurd; Figdor, Carl G.Nature Reviews Immunology (2007), 7 (10), 790-802CODEN: NRIABX; ISSN:1474-1733. (Nature Publishing Group)A review. The realization that dendritic cells (DCs) orchestrate innate and adaptive immune responses has stimulated research on harnessing DCs to create more effective vaccines. Early clin. trials exploring autologous DCs that were loaded with antigens ex vivo to induce T-cell responses have provided proof of principle. Here, the authors discuss how direct targeting of antigens to DC surface receptors in vivo might replace laborious and expensive ex vivo culturing, and facilitate large-scale application of DC-based vaccination therapies.
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139Ciejka, J.; Wolski, K.; Nowakowska, M.; Pyrc, K.; Szczubiałka, K. Biopolymeric Nano/Microspheres for Selective and Reversible Adsorption of Coronaviruses. Mater. Sci. Eng., C 2017, 76, 735– 742, DOI: 10.1016/j.msec.2017.03.047139https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXltVWhtbs%253D&md5=fb115099d070e189ed074f796dbfd742Biopolymeric nano/microspheres for selective and reversible adsorption of coronavirusesCiejka, Justyna; Wolski, Karol; Nowakowska, Maria; Pyrc, Krzysztof; Szczubialka, KrzysztofMaterials Science & Engineering, C: Materials for Biological Applications (2017), 76 (), 735-742CODEN: MSCEEE; ISSN:0928-4931. (Elsevier B.V.)A novel biopolymeric material in the form of nano/microspheres was developed which was capable of adsorbing coronaviruses. The biopolymer was obtained by crosslinking of chitosan (CHIT) with genipin, a nontoxic compd. of plant origin, in inverted emulsion and reacting the chitosan nano/microspheres obtained (CHIT-NS/MS) with glycidyltrimethyl-ammonium chloride (GTMAC). As a result the nano/microspheres of N-(2-hydroxypropyl)-3-trimethyl chitosan (HTCC-NS/MS) were obtained. HTCC-NS/MS were studied as the adsorbents of human coronavirus NL63 (HCoV-NL63), mouse hepatitis virus (MHV), and human coronavirus HCoV-OC43 particles in aq. virus suspensions. By studying cytopathic effect (CPE) caused by these viruses and performing PCR analyses it was found HTCC-NS/MS strongly adsorb the particles of HCoV-NL63 virus, moderately adsorb mouse hepatitis virus (MHV) particles, but do not adsorb HCoV-OC43 coronavirus. The adsorption capacity of HTCC-NS/MS well correlated with the antiviral activity of sol. HTCC against a given virus. Importantly, it was shown that HCoV-NL63 particles could be desorbed from the HTCC-NS/MS surface with a salt soln. of high ionic strength with retention of virus virulence. The obtained material may be applied for the removal of coronaviruses, purifn. and concn. of virus samples obtained from biol. matrixes and for purifn. of water from pathogenic coronaviruses.
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140Xu, Y.; Yuen, P.-W.; Lam, J. K. -W. Intranasal DNA Vaccine for Protection against Respiratory Infectious Diseases: The Delivery Perspectives. Pharmaceutics 2014, 6, 378– 415, DOI: 10.3390/pharmaceutics6030378140https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhs12qtL%252FJ&md5=d92affc86a4dfd5239fa92b4124ccb8eIntranasal DNA vaccine for protection against respiratory infectious diseases: the delivery perspectivesXu, Yingying; Yuen, Pak-Wai; Lam, Jenny Ka-WingPharmaceutics (2014), 6 (3), 378-415CODEN: PHARK5; ISSN:1999-4923. (MDPI AG)A review. Intranasal delivery of DNA vaccines has become a popular research area recently. It offers some distinguished advantages over parenteral and other routes of vaccine administration. Nasal mucosa as site of vaccine administration can stimulate respiratory mucosal immunity by interacting with the nasopharyngeal-assocd. lymphoid tissues (NALT). Different kinds of DNA vaccines are investigated to provide protection against respiratory infectious diseases including tuberculosis, coronavirus, influenza and respiratory syncytial virus (RSV) etc. DNA vaccines have several attractive development potential, such as producing cross-protection towards different virus subtypes, enabling the possibility of mass manuf. in a relatively short time and a better safety profile. The biggest obstacle to DNA vaccines is low immunogenicity. One of the approaches to enhance the efficacy of DNA vaccine is to improve DNA delivery efficiency. This review provides insight on the development of intranasal DNA vaccine for respiratory infections, with special attention paid to the strategies to improve the delivery of DNA vaccines using non-viral delivery agents.
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141Tse, G. M. -K.; To, K.-F.; Chan, P. K.-S.; Lo, A. W. I.; Ng, K.-C.; Wu, A.; Lee, N.; Wong, H.-C.; Mak, S.-M.; Chan, K.-F.; Hui, D. S. C.; Sung, J. J. -Y.; Ng, H.-K. Pulmonary Pathological Features in Coronavirus Associated Severe Acute Respiratory Syndrome (SARS). J. Clin. Pathol. 2004, 57, 260– 265, DOI: 10.1136/jcp.2003.013276141https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD2c7jsVGltw%253D%253D&md5=6c43791207beb06113fe50b0e43f93edPulmonary pathological features in coronavirus associated severe acute respiratory syndrome (SARS)Tse G M-K; To K-F; Chan P K-S; Lo A W I; Ng K-C; Wu A; Lee N; Wong H-C; Mak S-M; Chan K-F; Hui D S C; Sung J J-Y; Ng H-KJournal of clinical pathology (2004), 57 (3), 260-5 ISSN:0021-9746.BACKGROUND: Severe acute respiratory syndrome (SARS) became a worldwide outbreak with a mortality of 9.2%. This new human emergent infectious disease is dominated by severe lower respiratory illness and is aetiologically linked to a new coronavirus (SARS-CoV). METHODS: Pulmonary pathology and clinical correlates were investigated in seven patients who died of SARS in whom there was a strong epidemiological link. Investigations include a review of clinical features, morphological assessment, histochemical and immunohistochemical stainings, ultrastructural study, and virological investigations in postmortem tissue. RESULTS: Positive viral culture for coronavirus was detected in most premortem nasopharyngeal aspirate specimens (five of six) and postmortem lung tissues (two of seven). Viral particles, consistent with coronavirus, could be detected in lung pneumocytes in most of the patients. These features suggested that pneumocytes are probably the primary target of infection. The pathological features were dominated by diffuse alveolar damage, with the presence of multinucleated pneumocytes. Fibrogranulation tissue proliferation in small airways and airspaces (bronchiolitis obliterans organising pneumonia-like lesions) in subpleural locations was also seen in some patients. CONCLUSIONS: Viable SARS-CoV could be isolated from postmortem tissues. Postmortem examination allows tissue to be sampled for virological investigations and ultrastructural examination, and when coupled with the appropriate lung morphological changes, is valuable to confirm the diagnosis of SARS-CoV, particularly in clinically unapparent or suspicious but unconfirmed cases.
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142Gu, J.; Korteweg, C. Pathology and Pathogenesis of Severe Acute Respiratory Syndrome. Am. J. Pathol. 2007, 170, 1136– 1147, DOI: 10.2353/ajpath.2007.061088142https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXkvFymsLw%253D&md5=9762a0dc94960ea810377891759f07bbPathology and pathogenesis of severe acute respiratory syndromeGu, Jiang; Korteweg, ChristineAmerican Journal of Pathology (2007), 170 (4), 1136-1147CODEN: AJPAA4; ISSN:0002-9440. (American Society for Investigative Pathology)A review. Severe acute respiratory syndrome (SARS) is an emerging infectious viral disease characterized by severe clin. manifestations of the lower respiratory tract. The pathogenesis of SARS is highly complex, with multiple factors leading to severe injury in the lungs and dissemination of the virus to several other organs. The SARS coronavirus targets the epithelial cells of the respiratory tract, resulting in diffuse alveolar damage. Several organs/cell types may be infected in the course of the illness, including mucosal cells of the intestines, tubular epithelial cells of the kidneys, neurons of the brain, and several types of immune cells, and certain organs may suffer from indirect injury. Extensive studies have provided a basic understanding of the pathogenesis of this disease. In this review we describe the most significant pathol. features of SARS, explore the etiol. factors causing these pathol. changes, and discuss the major pathogenetic mechanisms. The latter include dysregulation of cytokines/chemokines, deficiencies in the innate immune response, direct infection of immune cells, direct viral cytopathic effects, down-regulation of lung protective angiotensin converting enzyme 2, autoimmunity, and genetic factors. It seems that both abnormal immune responses and injury to immune cells may be key factors in the pathogenesis of this new disease.
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143Nascimento, T. L.; Hillaireau, H.; Fattal, E. Nanoscale Particles for Lung Delivery of siRNA. J. Drug Delivery Sci. Technol. 2012, 22, 99– 108, DOI: 10.1016/S1773-2247(12)50010-9143https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XkvFyisbs%253D&md5=cc42c312220019972db3ff63d5d588f4Nanoscale particles for lung delivery of siRNANascimento, T. L.; Hillaireau, H.; Fattal, E.Journal of Drug Delivery Science and Technology (2012), 22 (1), 99-108CODEN: JDDSAL; ISSN:1773-2247. (Editions de Sante)A review. Small interfering RNAs (siRNAs) are potent mols. capable of blocking gene expression after entering cell cytoplasm. Despite their strong efficacy, they need to be carried by nanoscale delivery systems that can protect them against degrdn. in biol. fluids, increase their cellular uptake and favor their subcellular distribution. Several studies have highlighted the potential of local pulmonary delivery of siRNAs for the treatment of lung diseases. For this purpose, nanoscale delivery systems were addressed to target passively or actively the target cell. This review discusses the possibilities of approaching lung delivery of nanoscale particles carrying siRNAs.
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144Wang, F.; Kream, R. M.; Stefano, G. B. An Evidence Based Perspective on mRNA-SARS-CoV-2 Vaccine Development. Med. Sci. Monit. 2020, 26, 924700, DOI: 10.12659/MSM.924700There is no corresponding record for this reference.
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145Liu, C.; Zhou, Q.; Li, Y.; Garner, L. V.; Watkins, S. P.; Carter, L. J.; Smoot, J.; Gregg, A. C.; Daniels, A. D.; Jervey, S.; Albaiu, D. Research and Development on Therapeutic Agents and Vaccines for Covid-19 and Related Human Coronavirus Diseases. ACS Cent. Sci. 2020, 6, 315– 331, DOI: 10.1021/acscentsci.0c00272145https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXkslWrsbo%253D&md5=fa29fb4cc3353a140e3a6a74059a99b1Research and Development on Therapeutic Agents and Vaccines for COVID-19 and Related Human Coronavirus DiseasesLiu, Cynthia; Zhou, Qiongqiong; Li, Yingzhu; Garner, Linda V.; Watkins, Steve P.; Carter, Linda J.; Smoot, Jeffrey; Gregg, Anne C.; Daniels, Angela D.; Jervey, Susan; Albaiu, DanaACS Central Science (2020), 6 (3), 315-331CODEN: ACSCII; ISSN:2374-7951. (American Chemical Society)A review. Since the outbreak of the novel coronavirus disease COVID-19, caused by the SARS-CoV-2 virus, this disease has spread rapidly around the globe. Considering the potential threat of a pandemic, scientists and physicians have been racing to understand this new virus and the pathophysiol. of this disease to uncover possible treatment regimens and discover effective therapeutic agents and vaccines. To support the current research and development, CAS has produced a special report to provide an overview of published scientific information with an emphasis on patents in the CAS content collection. It highlights antiviral strategies involving small mols. and biologics targeting complex mol. interactions involved in coronavirus infection and replication. The drug-repurposing effort documented herein focuses primarily on agents known to be effective against other RNA viruses including SARS-CoV and MERS-CoV. The patent anal. of coronavirus-related biologics includes therapeutic antibodies, cytokines, and nucleic acid-based therapies targeting virus gene expression as well as various types of vaccines. More than 500 patents disclose methodologies of these four biologics with the potential for treating and preventing coronavirus infections, which may be applicable to COVID-19. The information included in this report provides a strong intellectual groundwork for the ongoing development of therapeutic agents and vaccines.
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146Frede, A.; Neuhaus, B.; Knuschke, T.; Wadwa, M.; Kollenda, S.; Klopfleisch, R.; Hansen, W.; Buer, J.; Bruder, D.; Epple, M.; Westendorf, A. M. Local Delivery of siRNA-Loaded Calcium Phosphate Nanoparticles Abates Pulmonary Inflammation. Nanomedicine 2017, 13, 2395– 2403, DOI: 10.1016/j.nano.2017.08.001146https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtlegsb3K&md5=59331b85b1b1fc6333750c5c68de0941Local delivery of siRNA-loaded calcium phosphate nanoparticles abates pulmonary inflammationFrede, Annika; Neuhaus, Bernhard; Knuschke, Torben; Wadwa, Munisch; Kollenda, Sebastian; Klopfleisch, Robert; Hansen, Wiebke; Buer, Jan; Bruder, Dunja; Epple, Matthias; Westendorf, Astrid M.Nanomedicine (New York, NY, United States) (2017), 13 (8), 2395-2403CODEN: NANOBF; ISSN:1549-9634. (Elsevier)The local interference of cytokine signaling mediated by siRNA-loaded nanoparticles might be a promising new therapeutic approach to dampen inflammation during pulmonary diseases. For the local therapeutic treatment of pulmonary inflammation, we produced multi-shell nanoparticles consisting of a calcium phosphate core, coated with siRNAs directed against pro-inflammatory mediators, encapsulated into poly(lactic-co-glycolic acid), and coated with a final outer layer of polyethylenimine. Nasal instillation of nanoparticles loaded with a mixt. of siRNAs directed against different cytokines to mice suffering from TH1 cell-mediated lung inflammation, or of siRNA directed against NS-1 in an influenza infection model led to a significant redn. of target gene expression which was accompanied by distinct amelioration of lung inflammation in both models. Thus, this study provides strong evidence that the specific and local modulation of the inflammatory response by CaP/PLGA nanoparticle-mediated siRNA delivery could be a promising approach for the treatment of inflammatory disorders of the lung.
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147Dykman, L. A.; Khlebtsov, N. G. Immunological Properties of Gold Nanoparticles. Chem. Sci. 2017, 8, 1719– 1735, DOI: 10.1039/C6SC03631G147https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhvVKgtLfE&md5=03448b78fd528a6017504d1dde11a349Immunological properties of gold nanoparticlesDykman, Lev A.; Khlebtsov, Nikolai G.Chemical Science (2017), 8 (3), 1719-1735CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)In the past decade, gold nanoparticles have attracted strong interest from the nanobiotechnol. community owing to the significant progress made in robust and easy-to-make synthesis technologies, in surface functionalization, and in promising biomedical applications. These include bioimaging, gene diagnostics, anal. sensing, photothermal treatment of tumors, and targeted delivery of various biomol. and chem. cargos. For the last-named application, gold nanoparticles should be properly fabricated to deliver the cargo into the targeted cells through effective endocytosis. In this review, we discuss recent progress in understanding the selective penetration of gold nanoparticles into immune cells. The interaction of gold nanoparticles with immune cell receptors is discussed. As distinct from other published reviews, we present a summary of the immunol. properties of gold nanoparticles. This review also summarizes what is known about the application of gold nanoparticles as an antigen carrier and adjuvant in immunization for the prepn. of antibodies in vivo. For each of the above topics, the basic principles, recent advances, and current challenges are discussed. Thus, this review presents a detailed anal. of data on interaction of gold nanoparticles with immune cells. Emphasis is placed on the systematization of data over prodn. of antibodies by using gold nanoparticles and adjuvant properties of gold nanoparticles. Specifically, we start our discussion with current data on interaction of various gold nanoparticles with immune cells. The next section describes existing technologies to improve prodn. of antibodies in vivo by using gold nanoparticles conjugated with specific ligands. Finally, we describe what is known about adjuvant properties of bare gold or functionalized nanoparticles. In the Conclusion section, we present a short summary of reported data and some challenges and perspectives.
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148Comber, J. D.; Bamezai, A. Gold Nanoparticles (AuNPs): A New Frontier in Vaccine Delivery. J. Nanomed. Biother. Discovery 2015, 5, e139, DOI: 10.4172/2155-983X.1000e139148https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXmtVGku7Y%253D&md5=a7c20256e9843780d398e1c2f540adbaGold nanoparticles (AuNPs): a new frontier in vaccine deliveryComber, Joseph D.; Bamezai, AnilJournal of Nanomedicine & Biotherapeutic Discovery (2015), 5 (4), 139/1-139/4CODEN: JNBDB3; ISSN:2155-983X. (OMICS International)There is no expanded citation for this reference.
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149Niikura, K.; Matsunaga, T.; Suzuki, T.; Kobayashi, S.; Yamaguchi, H.; Orba, Y.; Kawaguchi, A.; Hasegawa, H.; Kajino, K.; Ninomiya, T.; Ijiro, K.; Sawa, H. Gold Nanoparticles as a Vaccine Platform: Influence of Size and Shape on Immunological Responses In Vitro and In Vivo. ACS Nano 2013, 7, 3926– 3938, DOI: 10.1021/nn3057005149https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXmvVylsrw%253D&md5=7b184b14dba10fafe46b9f63850b2e7cGold Nanoparticles as a Vaccine Platform: Influence of Size and Shape on Immunological Responses in Vitro and in VivoNiikura, Kenichi; Matsunaga, Tatsuya; Suzuki, Tadaki; Kobayashi, Shintaro; Yamaguchi, Hiroki; Orba, Yasuko; Kawaguchi, Akira; Hasegawa, Hideki; Kajino, Kiichi; Ninomiya, Takafumi; Ijiro, Kuniharu; Sawa, HirofumiACS Nano (2013), 7 (5), 3926-3938CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)This paper demonstrates how the shape and size of gold nanoparticles (AuNPs) affect immunol. responses in vivo and in vitro for the prodn. of antibodies for West Nile virus (WNV). The authors prepd. spherical (20 and 40 nm in diam.), rod (40×10 nm), and cubic (40×40×40 nm) AuNPs as adjuvants and coated them with WNV envelope (E) protein. The authors measured anti-WNVE antibodies after inoculation of these WNVE-coated AuNPs (AuNP-Es) into mice. The 40 nm spherical AuNP-Es (Sphere40-Es) induced the highest level of WNVE-specific antibodies, while rod AuNP-Es (Rod-Es) induced only 50% of that of Sphere40-E. To examine the mechanisms of the shape-dependent WNVE antibody prodn., the authors next measured the efficiency of cellular uptake of AuNP-Es into RAW264.7 macrophage cells and bone-marrow-derived dendritic cells (BMDCs) and the subsequent cytokine secretion from BMDCs. The uptake of Rod-Es into the cells proceeded more efficiently than those of Sphere-Es or cubic WNVE-coated AuNPs (Cube-Es), suggesting that antibody prodn. was not dependent on the uptake efficiency of the different AuNP-Es. Cytokine prodn. from BMDCs treated with the AuNP-Es revealed that only Rod-E-treated cells produced significant levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18), indicating that Rod-Es activated inflammasome-dependent cytokine secretion. Meanwhile, Sphere40-Es and Cube-Es both significantly induced inflammatory cytokine prodn., including tumor necrosis factor-α (TNF-α), IL-6, IL-12, and granulocyte macrophage colony-stimulating factor (GM-CSF). These results suggested that AuNPs are effective vaccine adjuvants and enhance the immune response via different cytokine pathways depending on their sizes and shapes.
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