Introduction
Coronaviruses (CoVs) belong to the Coronaviridae family, which includes a group of enveloped, positive, single-RNA viruses [1]. Such viruses that bear the largest genome among RNA viruses were called ‘CoVs’ because of their crown morphology under an electron microscope. CoVs are structurally nongenomic and share a common organization [2]. Around two-thirds of the genome consists of two large overlapping open reading frames (ORF1a and ORF1b), which are translated into the polyproteins pp1a and pp1ab replicate [3,4]. The remainder of the genome contains structural open reading frame (ORF) proteins, including spike (S), envelope (E), membrane (M), and nucleoprotein (N). Different lineages of CoVs encode a variety of lineage-specific accessory proteins too [5]. Thus, the accurate detection of coronavirus is an important issue.
CoVs are classified into four genera (alpha-CoV, beta-CoV, gamma-CoV, and delta-CoV) based on the difference in protein sequences, of which the beta-CoV genera contain the most HCoVs [6,7]. Seven human CoVs (HCoVs) have been identified. Among them are alpha-CoVs, HCoV-229E, and HCoV-NL63. The remaining five beta-CoVs are HCoV-OC43, HCoV-HKU1, extreme acute respiratory coronavirus syndrome (SARS-CoV), Middle East coronavirus respiratory syndrome (MERS-CoV), and SARS-CoV-2 [8–11]. Conversely, SARS-CoV, MERS-CoV, and the recently identified SARS-CoV-2 are highly pathogenic, triggering a significant lower respiratory tract infection in comparatively more patients at higher risk of developing acute respiratory distress syndrome (ARDS) and extrapulmonary manifestations [12].
Spike proteins SARS-CoV-2 and SARS-CoV share a similarity of 76.5% in amino acid sequences [13], and most significantly, the spike proteins SARS-CoV-2 and SARS-CoV have a high homology degree [14,15]. Over-expression of human ACE2 increased disease severity in a mouse model of SARS-Cov infection, demonstrating that viral cell entry is a key stage [16]. Injecting SARS-CoV spike into mice exacerbated lung injury; this injury was significantly attenuated by blocking the pathway to renin--angiotensin and depended on the expression of ACE2 [17]. Consequently, ACE2 is not only the virus entry receptor for pathogenesis of SARS-CoV but also protects against lung injury. Additionally, the SARS-CoV-2 spike protein binds directly to the host cell surface of the ACE2 receptor to facilitate virus entry and replication.
Therefore, knowing how this virus affects human proteins, plays a key role in making pharmacological strategies a priority [4,18]. The COVID-19 epidemic has presented the world with major medical, technological, political, and moral challenges [19]. In this study, we will look at the comparison and contrast of the various HCoVs from a virus evolution and genome recombination perspective, which in turn will assist in the creation of new drugs that interact with SARS-CoV-2 viral N protein and viral replication, and highly related SARS-CoV virus.
Furthermore, it is attempted to highlight COVID-19's molecular mechanisms and pathogenesis to demonstrate the best ways to help medical staff diagnose infection rapidly and reliably, and survive patient life and prevent infection from spreading. Through this study, various currently available approaches to coronavirus detection will be analyzed. It is expected to help researchers develop rapid and accurate detection techniques.
Analysis of the clinical characteristics of human coronaviruses
The first strain of HCoV-229E has been isolated from the patients with upper respiratory tract infection breathing tract [20]. Patients diagnosed with HCoV-229E have typical symptoms of cold, including headache, malaise, sneezing and sore throat, cough, and fever [21]. It was isolated from the culture of the organ, and the subsequent serial passage of suckling mice in the brains [22]. HCoV-OC43 isolated from organ culture, and the clinical features of HCoV-OC43 infection appear to be close to those of HCoV-229E infection, which are symptomatically isolated from other pathogens in respiratory tract infections, such as influenza A viruses and rhinoviruses [2]. HCoV-229E and HCoV-OC43 are both widely distributed and tend to be transmitted mostly during the winter season in a temperate climate [23]. The incubation period for these two viruses usually is less than 1 week, along with an outbreak of around 2 weeks [24].
Patients with extreme acute respiratory coronavirus syndrome (SARS-CoV) initially have myalgia, headache, vomiting, nausea, pain, and chills, followed by late signs of dyspnea, cough, and respiratory distress [25]. The specific laboratory abnormalities of SARS are lymphopenia, deranged liver function tests, and raised creatine kinase [26,27]. SARS patients also experience diffuse alveolar damage, the proliferation of the epithelial cells, and increased macrophages [28]. In addition to the lower respiratory tract, in these severe cases, several organs, including the gastrointestinal tract, liver, and kidney, may also be compromised, generally followed by a cytokine storm, This could be lethal, especially in immunocompromised patients [29].
Coryza, conjunctivitis, fever, and bronchiolitis are normal in the HCoV-NL63 outbreak. Their peak occurrence is in early summer, spring, and winter [30].
HCoV-NL63 triggers obstructive laryngitis also referred to as croup [31]. The acute asthmatic exacerbation of HCoV-HKU1 has been reported, in addition to community-acquired pneumonia and bronchiolitis [32]. HCoV-HKU1 has been found worldwide, causing mild respiratory diseases, similar to HCoV-NL63, HCoV-229E, and HCoV-OC43 [33]. All four of these community-acquired HCoVs were well suited to humans, and are therefore, less likely and mutating and developing highly pathogenic diseases [34]. In general, they often become less virulent or pathogenic as these HCoVs learn the ability to transmit efficiently and to sustain themselves continuously inside humans [35]. MERS symptoms are similar to those of SARS, distinguished by recurrent severe pneumonia [36]. Like SARS, most MERS patients have had acute renal failure, which has so far been exceptional among HCoV-induced MERS diseases [37].
SARS-CoV-2 causes severe respiratory infections, such as SARS-CoV and MERS-CoV, which are described as dyspnea, cough, and fever [38]. Moreover, some patients also suffer from diarrhea [39]. Pneumonia is one of the most serious signs and may progress quickly into the condition of acute respiratory distress [40]. Although SARS-CoV and SARS-CoV-2 are very similar because of homology of 82% high nucleotide sequence, they cluster into various branches of the phylogenetic tree [5]. Compared with SARS-CoV and MERS-CoV, SARS-CoV-2 is potentially less pathogenic but more conveyable [41]. Comparing the SARS-CoV-2 to the other six HCoVs demonstrate similarities and very interesting variations [42]. Firstly, the period of incubation and the duration of the HCoV disease course are quite similar [43]. SARS-CoV-2 is following the general pattern of the six other HCoVs in this regard. Second, the intensity of symptoms of COVID-19 lies between SARS-CoV and the four community-acquired HCoVs (i.e. HCoV-229E, HCoV-HKU1, HCoV-OC43, and HCoV-NL63) [37]. On one hand, SARS-CoV-2 infection exhibits features that are most often seen during community-acquired HCoV infection, including the presentation of nonspecific, moderate, or even no symptoms. Second, SARS-CoV-2 transmission often demonstrates interesting characteristic patterns in community-acquired SARS-CoVs and HCoVs (Table 1).
Table 1 - Comparison of clinical features of the seven human coronaviruses.
| HCoVs |
Classification |
Clinical symptoms |
Representative References |
| HCoV-229E |
Alpha-CoV |
Malaise, headache, nasal discharge, sneezing, sore throat, fever and cough |
[20] |
| HCoV-OC43 |
Beta-CoV, lineage A |
Malaise, headache, nasal discharge, sneezing, sore throat |
[2] |
| SARS-CoV |
Beta-CoV, lineage B |
Malaise, headache, myalgia, dyspnea, diarrhea, fever and dry cough |
[25] |
| HCoV-NL63 |
Alpha-CoV |
Cough, rhinorrhea, tachypnea, fever, hypoxia, croup |
[31] |
| HCoV-HKU1 |
Beta-CoV, lineage A |
fever, running nose, cough, dyspnea |
[32] |
| MERS-CoV |
Beta-CoV, lineage C |
fever, chills, cough, myalgia, pneumonia, arthralgia, diarrhea and vomiting |
[36] |
| SARS-CoV-2 |
Beta-CoV, lineage B |
Myalgia, dyspnea, fever, headache, diarrhea, dry cough |
[5] |
Specific features of SARS CoV 2 genome
Analysis of phylogenetic of SARS-CoV-2 illustrated that this virus belonged to lineage B of the betacoronavirus genus. SARS-CoV-2 includes a high percentage of similarity with SARS-CoV as well as, the genomic analogy of viruses identified of two particular characteristics of SARS CoV 2, I: based on structural studies and biochemical tests, SARS CoV 2 has been optimized for binding to the human receptor ACE2, II: SARS CoV 2 spike protein has a functional polybasic (Furine) cleavage site in the S1-S2 region, which results in the further prediction of three O-linked glycans around the site by the addition of 12 nucleotides [5,44,45].
Mutation in the domain SARS CoV 2 receptor binding
The most variable component of the coronavirus genome is the receptor-binding domain (RBD) in the spike protein [46,47]. Six RBD amino acids are essential for binding to ACE2 receptors and for deciding host receptor binding to SARS CoV, whose coordinates are based on (SARS CoV) Y442, L472, N479, D480, T487, and Y4911, which correspond to L455, F486, Q493, S494, N501, and Y505 in (SARS CoV 2), in which five of the six cases vary between SARS CoV 2 and SARS CoV [15,48].
Polybasic furin cleavage site and O-linked glycans
The next noticeable characteristic of SARS CoV 2 is a polybasic cleavage site (RRAR) in the spike protein at the junction between S1 and S2. This allows it to be effective through furin and other proteases, and play a role in identifying viral infection and binding to the host cell [43]. In addition, in this site, SARS-CoV-2 can insert a precursor proline by inserted sequence RRAR. Thus, it is anticipated that proline will add O glycans linked to S673, T678, and S686 that fill the gap portion and are specific to SARS CoV 2 [44].
SARS-CoV-2 and the severe coronavirus acute respiratory syndrome
The sequence of hundreds of SARS-CoV-2 virus isolates has shown that there is a near relationship between two bats-derived SARS-like coronaviruses as well as, RBD of SARS-CoV-2 is similar to the SARS-CoV RBD, suggesting a probable common receptor of the host cell [49]. In-vitro and in-vivo investigations have shown that these strains of coronavirus have an analogous receptor-binding domain structure in the spike (S) protein for host angiotensin-converting enzyme (ACE2) proteins [50,51]. In mice infected with SARS-CoV, human ACE2 over-expression increased the severity of the disease, demonstrated that the ACE2-dependent entrance of the virus into cells is a critical step [52]. Injection of SARS-CoV spike into mice has been reported to decrease levels of ACE2 expression, thus aggravating lung injury [50,51]. In addition, studies have shown that ACE2 acts both as the SARS-CoV entry receptor and to defend the lung against injury [17].
Using the angiotensin-converting enzyme 2 receptor (SARS-CoV) to facilitate the viral entry into target cells
Cryo-EM is a type of transmission electron microscope (TEM) in which the sample studied in refrigeration (liquid nitrogen temperature) is examined [53]. In line with this, there are three recent cryo-EM studies, which demonstrated that the new coronavirus enters human cells using a glycoprotein called ‘SARS-CoV-2 Spike’ or ‘S’ that binds to the protein of cell membrane, ‘angiotensin-converting enzyme 2’ (ACE2), as well as they, discovered that the ability of (SARS-CoV-2) to bind receptors 10 up to 20 times more efficient than another coronavirus [15,48,54]. The prerequisite for a coronavirus attack on the host cell is bound to the receptor [55]. After that, viral spike protein through cathepsin acid-dependent proteolysis, TMPRRS2 or furin protease breaks down and then integrates with the viral envelope to cell membranes [56]. The spike is a big clover-shaped trimmer that can be broken down by proteases into an RBD receptor-binding domain-containing ns1 subunit and a region of C terminal S2 [57].
Unlike other coronavirus proteins, the spike protein contains the most complex sequence of amino acids, which is the best way to conform to their hosts [15,58,59]. The glycoprotein, or SARS-CoV-2 spike, is a combination of protein and carbohydrate that it has been glycosylated with small chains of oligosaccharides (sugars) but does not contain phosphoric acid, purine or pyrimidine. On the other hand, ‘ACE2’, is an exopeptidase that converts angiotensin-1 to 9 (Ang 1–9) or it is led to converting angiotensin-II (Ang-II) to angiotensin 1–7 (Ang 1–7) [15,58,59]. This enzyme has a direct effect on heart function and is mostly expressed in the inner layer of blood vessels, heart, and kidneys [10,60,61]. When coronavirus infects a human cell, the ‘S’ protein is subdivided into ‘S1’ and ‘S2’ subunits. ‘S1’ encompasses the RBD, thus ‘COVID-19’ can bind to the peptidase domain directly in ‘ACE2’ [62–64]. It is assumed that the ‘S2’ subunit has a role in cell fusion (Fig. 1).
;)
Fig. 1:
Schematic illustration of therapeutic mechanism against corona virus disease-2019 in the context of host pathways and viral entry mechanism.
Cleavage of SARS-COV-2 S proteins by host furin
As mentioned, The S protein of SARS-CoV-2 binds with a stronger affinity to human ACE2 receptors than that of the SARS-CoV virus [54,65], it can be because of a furin-like cleavage site (682RRAR/S686) implanted in the S1/S2 SARS-CoV-2 virus protease cleavage site. The spike protein (S1 region) is in charge of binding to the host cell receptor ACE2, where the S2 region is responsible for viral RNA fusion and cellular membranes [54,66]. Such polybasic furin sites in hemagglutinin proteins have most also been observed in highly virulent influenza viruses. Therefore, the addition of the furin site can increase the ability of this new SARS-CoV-2 to bind and invade human ACE2-expressed cells [67].
SARS-CoV-2 invades host cells via a CD147-spike protein
CD147 is a transmembrane glycoprotein that belongs to the superfamily of immunoglobulins, which is implicated in the development of cancers, plasmodium invasions, and virus infections [68–71]. CD147 express in by various sorts of cells, including epithelial cells, endothelial cells, and leukocytes [72]. Previously, studies have been shown that CD147 plays a working role in promoting SARS-CoV invasion of host cells, and that CD147-antagonistic peptide-9 has a high binding capacity to HEK293 cells and a SARS-CoV inhibitory effect [71]. Nowadays, scientist reported that SARS-CoV-2 invades host cells through a new way of CD147-spike protein. The host-cell-expressed basigin (CD147) may bind SARS-CoV-2 spike protein and possibly be involved in the invasion of host cells [73,74]. Consequently, Meplazumab has been studied in patients with SARS-CoV-2 pneumonia as a humanized anti-CD147 antibody [74].
Human angiotensin-converting enzyme 2 in complex with B0AT1 and pathogenesis of coronavirus disease-2019
Recent studies show that ACE2 moonlights as the chaperone for the membrane trafficking of an amino acid transporter. B0AT1, also known as (SLC6A19) mediates the absorption of neutral amino acids into the intestinal cells using a sodium-related method as well as whose surface expression in intestinal cells requires ACE2 [75–78]. Newly, scientists presented modeling of the 2.9 Å resolution cryo-EM configuration of full-length human ACE2 in complex with B0AT1. The investigations indicating that human ACE2 in complex with B0AT1 can bind two spike proteins simultaneously so, this data can be an important clue to the molecular basis for coronavirus detection and infection [60].
Molecular pathways and therapeutic target
The lung seems to be the most vulnerable goal organ as the lung's vast surface area makes it particularly susceptible to inhaled viruses [79]. Gene ontology enrichment research revealed that ACE2-expressing AECII has high rates of several viral process-related genes including viral process regulatory genes, viral life cycle, viral assembly, and replication of viral genomes, indicating that the ACE2-expressing AECII facilitates the replication of coronavirus in the lungs [80]. ACE2 receptor expression can also be observed in multiple extrapulmonary tissues, such as the heart, intestine, endothelium, and kidney. Significantly, ACE2 is expressed so much on the luminal surface of intestinal epithelial cells, acting as a co-receptor for the absorption of nutrients, especially for the resorption of amino acid from food [17]. Therefore, it is predicted that the intestine may also be an essential SARS-CoV-2 entry site.
Potential pathways to corona virus disease-2019, mediated by angiotensin-converting enzyme 2
Spike protein vaccine
The creation of a vaccine based on a spike 1 subunit of protein could be contingent on the reality that ACE2 is the receptor for SARS-CoV-2 [81]. Cell lines, which promote viral replication in the presence of ACE2 can be the most effective in the large-scale production of vaccines [48].
Inhibition of transmembrane protease serine 2 activity
Many experiments have described that the SARS spike protein engages ACE2 as an input receptor and then uses the TMPRSS2 cell serine protease for S protein priming by host cell proteases [56,63,64,82]. Recently, researchers have demonstrated that the serum form a convalescent SARS patient neutralized 2019-nCoV32 S-driven entry [56,63,64,82]. Therefore, A TMPRSS2 inhibitor has then blocked entry and may represent a therapeutic choice. In addition, initial spike protein priming by transmembrane protease serine 2 (TMPRSS2) is needed for SARS-input and viral dissemination via interaction with the ACE2 receptor [64]. A serine protease inhibitor, camostat mesylate, approved for the treatment of unknown diseases in Japan, has been shown to counteract the activity of TMPRSS2, and is thus a well tolerated alternative [83,84].
Blocking the angiotensin-converting enzyme 2 receptor
The interaction sites between ACE2 and SARS-CoV have been identified at the atomic level, and the associations between ACE2 and SARS-CoV-2 should also be true from the studies to date [85]. Therefore, one may target this site of interaction with antibodies or small molecules.
Delivering excessively soluble form of angiotensin-converting enzyme 2
In mice, it is proved that SARS-CoV downregulates ACE2 protein (but not ACE) via binding its spike protein, which leads to serious lung damage [51]. This indicates that excessive ACE2 can compete with SARS-CoV-2 not only to neutralize the virus but also to rescue cellular ACE2 function that adversely regulates the system of renin--angiotensin (RAS) to protect the lung against injury [86]. In addition, increased activity of the ACE and reduced availability of ACE2 lead to lung injury during lung injury caused by acid and ventilator. Therefore, the treatment of ACE2 in a soluble form may have dual functions: slowing the entry of the virus into cells, and thus viral distribution, and shielding the lung from damage [87] (Fig. 2).
Fig. 2:
Pathogenesis and transmission mechanism of Sars and Sars-CoV-2 by angiotensin-converting enzyme 2 receptor.
New treatment strategies for corona virus disease-2019
The ACE2 enzyme is a transgenic protein and the main entry point for the Coronavirus disease 2019 (COVID-19) into the host cell [88]. Decreased levels of the ACE2 enzyme in the cell are thought to help fight the infection. On the other hand, the presence of the ACE2 enzyme protects lung cells from damage caused by the virus by increasing the level of the angiotensin-1–7 dilating agent [89]. Thought to be an ACE2 human recombinant enzyme (rhACE2) is a new treatment for acute respiratory damage [90]. In this regard, scientists used a human recombinant solution (ACE2) to prevent the growth of SARS-CoV-2, investigation shows that recombinant human angiotensin-converting enzyme 2 (hrsACE2) has an inhibitory effect on the growth of the SARS-CoV-2 virus and was able to decrease the virus by 1000 to 5000 times compared with normal cell culture [91]. Moreover, blood and kidney arteries were used to display that SARS-CoV-2 could infect these tissues directly and multiply, which could be a potential cause of any organ failure and cardiovascular damage in serious COVID-19 cases [92]. These findings showed that hrsACE2 is also able to reduce SARS-CoV-2 infection in these organoids.
Conclusion
Many studies showed that ‘ACE2’ must undergo a molecular process in which it binds to another identical molecule so that it can become active or infectious or contagious. The resulting molecule can simultaneously bind two molecules of (COVID-19) S protein. The scientists also studied different binding models of ‘SARS-CoV-2 RBD’ than other related viruses and showing how subtle changes in the molecular binding sequence make the coronavirus structure stronger. The scientists concluded that their research could help global efforts to design new customized antibodies to target ‘ACE2’ or other coronavirus proteins that prevent coronavirus infection. The scientists also figured out that ‘COVID-19’ could be linked to another complex structure called ‘ACE2-B0AT1’. Previously, none of these molecular structures have been identified and now likely to be contributing to the production of antiviral drugs or even a vaccine that will be capable of inhibiting coronavirus targeting cells (ACE2).
Acknowledgements
This study was supported by the Drug Applied Research Center, Tabriz University of Medical Sciences.
Transparency document: The Transparency document associated with this article can be found, in the online version.
Funding: This study was supported by Tabriz University of Medical Sciences with grant number 65174.
Conflicts of interest
There are no conflicts of interest.
References
1. DeDiego ML, Nieto-Torres JL, Jiménez-Guardeño JM, Regla-Nava JA, Alvarez E, Oliveros JC, et al. Severe acute respiratory syndrome coronavirus envelope protein regulates cell stress response and apoptosis.
PLoS Pathog 2011; 7:e1002315.
2. Su S, Wong G, Shi W, Liu J, Lai AC, Zhou J, et al. Epidemiology, genetic recombination, and pathogenesis of coronaviruses.
Trends Microbiol 2016; 24:490–502.
3. Wong L-YR, Lui P-Y, Jin D-Y. A molecular arms race between host innate antiviral response and emerging human coronaviruses.
Virologica Sinica 2016; 31:12–23.
4. Khodadadi E, Maroufi P, Khodadadi E, Esposito I, Ganbarov K, Espsoito S, et al. Study of combining virtual screening and antiviral treatments of the Sars-CoV-2 (Covid-19).
Microb Pathog 2020; 146:104241.
5. Chan JF-W, Kok K-H, Zhu Z, Chu H, To KK-W, Yuan S, Yuen KY. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan.
Emerg Microbes Infect 2020; 9:221–236.
6. Anderson RM, Fraser C, Ghani AC, Donnelly CA, Riley S, Ferguson NM, et al. Epidemiology, transmission dynamics and control of SARS: the 2002–2003 epidemic.
Philos Trans R Soc Lond B Biol Sci 2004; 359:1091–1105.
7. Peeri NC, Shrestha N, Rahman MS, Zaki R, Tan Z, Bibi S, et al. The SARS, MERS and novel coronavirus (COVID-19) epidemics, the newest and biggest global health threats: what lessons have we learned?
Int J Epidemiol 2020; dyaa033.
8. Zhong N, Zheng B, Li Y, Poon L, Xie Z, Chan K, et al. Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People's Republic of China, in February, 2003.
Lancet 2003; 362:1353–1358.
9. Mobaraki K, Ahmadzadeh J. Current epidemiological status of Middle East respiratory syndrome coronavirus in the world from 1.1. 2017 to 17.1. 2018: a cross-sectional study.
BMC Infect Dis 2019; 19:351.
10. Zhao Y, Zhao Z, Wang Y, Zhou Y, Ma Y, Zuo W. Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov.
BioRxiv 2020.
11. Jiang S, Du L, Shi Z. An emerging coronavirus causing pneumonia outbreak in Wuhan, China: calling for developing therapeutic and prophylactic strategies.
Emerg Microbes Infect 2020; 9:275–277.
12. Ozma MA, Maroufi P, Khodadadi E, Köse Ş, Esposito I, Ganbarov K, et al. Clinical manifestation, diagnosis, prevention and control of SARS-CoV-2 (Covid-19) during the outbreak period.
Infez Med 2020; 28:153–165.
13. Xu X, Chen P, Wang J, Feng J, Zhou H, Li X, et al. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission.
Sci China Life Sci 2020; 63:457–460.
14. Li F. Receptor recognition and cross-species infections of SARS coronavirus.
Antiviral Res 2013; 100:246–254.
15. Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor recognition by the novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus.
J Virol 2020; 94:e00127–20.
16. Peck KM, Burch CL, Heise MT, Baric RS. Coronavirus host range expansion and Middle East respiratory syndrome coronavirus emergence: biochemical mechanisms and evolutionary perspectives.
Annu Rev Virol 2015; 2:95–117.
17. Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target.
Intensive Care Med 2020; 46:586–590.
18. Guarner J. Three emerging coronaviruses in two decades: the story of SARS, MERS, and now COVID-19. USA: Oxford University Press; 2020.
19. Fathizadeh H, Maroufi P, Momen-Heravi M, Dao S, Köse Ş, Ganbarov K, et al. Protection and disinfection policies against SARS-CoV-2 (COVID-19).
Infez Med 2020; 28:185–191.
20. Hamre D, Procknow JJ. A new virus isolated from the human respiratory tract.
Proc Soc Exp Biol Med 1966; 121:190–193.
21. Xia S, Xu W, Wang Q, Wang C, Hua C, Li W, et al. Peptide-based membrane fusion inhibitors targeting HCoV-229E spike protein HR1 and HR2 domains.
Int J Mol Sci 2018; 19:487.
22. Prill MM, Iwane MK, Edwards KM, Williams JV, Weinberg GA, Staat MA, et al. New Vaccine Surveillance Network. Human coronavirus in young children hospitalized for acute respiratory illness and asymptomatic controls.
Pediatr Infect Dis J 2012; 31:235–240.
23. Zhang S-F, Tuo J-L, Huang X-B, Zhu X, Zhang D-M, Zhou K, et al. Epidemiology characteristics of human coronaviruses in patients with respiratory infection symptoms and phylogenetic analysis of HCoV-OC43 during 2010–2015 in Guangzhou.
PloS One 2018; 13:e0191789.
24. Dijkman R, Jebbink MF, Gaunt E, Rossen JW, Templeton KE, Kuijpers TW, van der Hoek L. The dominance of human coronavirus OC43 and NL63 infections in infants.
J Clin Virol 2012; 53:135–139.
25. Zhou J, Chu H, Chan JF-W, Yuen K-Y. Middle East respiratory syndrome coronavirus infection: virus-host cell interactions and implications on pathogenesis.
Virol J 2015; 12:218.
26. Chan JF, Chan K-H, Kao RY, To KK, Zheng B-J, Li CP, et al. Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus.
J Infect 2013; 67:606–616.
27. Gholizadeh P, Safari R, Marofi P, Zeinalzadeh E, Pagliano P, Ganbarov K, et al. Alteration of liver biomarkers in patients with SARS-CoV-2 (COVID-19).
J Inflamm Res 2020; 13:285–292.
28. To KK, Hung IF, Chan JF, Yuen K-Y. From SARS coronavirus to novel animal and human coronaviruses.
J Thorac Dis 2013; 5: (Suppl 2): S103.
29. Yuan Y, Cao D, Zhang Y, Ma J, Qi J, Wang Q, et al. Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains.
Nat Commun 2017; 8:15092.
30. Donaldson EF, Haskew AN, Gates JE, Huynh J, Moore CJ, Frieman MB. Metagenomic analysis of the viromes of three North American bat species: viral diversity among different bat species that share a common habitat.
J Virol 2010; 84:13004–13018.
31. Pfefferle S, Oppong S, Drexler JF, Gloza-Rausch F, Ipsen A, Seebens A, et al. Distant relatives of severe acute respiratory syndrome coronavirus and close relatives of human coronavirus 229E in bats, Ghana.
Emerg Infect Dis 2009; 15:1377.
32. Woo PC, Lau SK, Tsoi H-W, Huang Y, Poon RW, Chu C-M, et al. Clinical and molecular epidemiological features of coronavirus HKU1–associated community-acquired pneumonia.
J Infect Dis 2005; 192:1898–1907.
33. Ramirez JA, Carrico R, Cavallazzi R, Beavin LA, Raghuram A, Burns MV, et al. Community-acquired pneumonia due to endemic human coronaviruses compared to 2019 novel coronavirus: a review.
The University of Louisville J Respir Infect 2020; 4:2.
34. Shirato K, Kawase M, Matsuyama S. Wild-type human coronaviruses prefer cell-surface TMPRSS2 to endosomal cathepsins for cell entry.
Virology 2018; 517:9–15.
35. Wu D, Wu T, Liu Q, Yang Z. The SARS-CoV-2 outbreak: what we know.
Int J Infect Dis 2020; 94:44–48.
36. Reusken C, Farag E, Jonges M, Godeke G-J, El-Sayed AM, Pas S, et al. Middle East respiratory syndrome coronavirus (MERS-CoV) RNA and neutralising antibodies in milk collected according to local customs from dromedary camels, Qatar, April 2014.
Euro surveill 2014; 19:20829.
37. Mohd HA, Al-Tawfiq JA, Memish ZA. Middle East respiratory syndrome coronavirus (MERS-CoV) origin and animal reservoir.
Virol J 2016; 13:87.
38. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.
Lancet 2020; 395:497–506.
39. van Doremalen N, Bushmaker T, Morris DH, Holbrook MG, Gamble A, Williamson BN, et al. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1.
New Engl J Med 2020; 382:1564–1567.
40. Lam TT-Y, Shum MH-H, Zhu H-C, Tong Y-G, Ni X-B, Liao Y-S, et al. Identification of 2019-nCoV related coronaviruses in Malayan pangolins in southern China.
Nature 2020; 583:282–285.
41. Lai C-C, Shih T-P, Ko W-C, Tang H-J, Hsueh P-R. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and corona virus disease-2019 (COVID-19): the epidemic and the challenges.
Int J Antimicrob Agents 2020; 105924.
42. Xu J, Zhao S, Teng T, Abdalla AE, Zhu W, Xie L, et al. Systematic comparison of two animal-to-human transmitted human coronaviruses: SARS-CoV-2 and SARS-CoV.
Viruses 2020; 12:244.
43. Yang Y, Peng F, Wang R, Guan K, Jiang T, Xu G, et al. The deadly coronaviruses: the 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China.
J Autoimmun 2020; 109:102434.
44. Andersen KG, Rambaut A, Lipkin WI, Holmes EC, Garry RF. The proximal origin of SARS-CoV-2.
Nat Med 2020; 26:450–452.
45. Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses.
Nat Microbiol 2020; 5:562–569.
46. Zhou P, Yang X-L, Wang X-G, Hu B, Zhang L, Zhang W, et al. Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin.
BioRxiv 2020; In press.
47. Wu F, Zhao S, Yu B. A new coronavirus associated with human respiratory disease in China.
Nature 2020; 579:265–269.
48. Walls AC, Park Y-J, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein.
Cell 2020.
49. Liu Z, Xiao X, Wei X, Li J, Yang J, Tan H, et al. Composition and divergence of coronavirus spike proteins and host ACE2 receptors predict potential intermediate hosts of SARS-CoV-2.
J Med Virol 2020; 92:595–601.
50. Imai Y, Kuba K, Rao S, Huan Y, Guo F, Guan B, et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure.
Nature 2005; 436:112–116.
51. Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus–induced lung injury.
Nature medicine 2005; 11:875–879.
52. Yang X-H, Deng W, Tong Z, Liu Y-X, Zhang L-F, Zhu H, et al. Mice transgenic for human angiotensin-converting enzyme 2 provide a model for SARS coronavirus infection.
Comp Med 2007; 57:450–459.
53. Yan 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.
54. Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh C-L, Abiona O, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation.
Science 2020; 367:1260–1263.
55. Ozma MA, Maroufi P, Khodadadi E, Köse S, Esposito I, Ganbarov K, et al. Clinical manifestation, diagnosis, prevention and control of SARS-CoV-2 (COVID-19) during the outbreak period.
56. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor.
Cell 2020; 181:271–280.
57. Tai W, He L, Zhang X, Pu J, Voronin D, Jiang S, et al. Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine.
Cell Mol Immunol 2020; 17:613–620.
58. Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early transmission dynamics in Wuhan, China, of novel coronavirus–infected pneumonia.
New Engl J Med 2020; 382:1199–1207.
59. Letko MC, Munster V. Functional assessment of cell entry and receptor usage for lineage B β-coronaviruses, including 2019-nCoV.
Nature Microbiology 2020; 5:562–569.
60. Zhou Q, Yan R, Zhang Y, Li Y, Xia L. Structure of dimeric full-length human ACE2 in complex with B0AT1.
bioRxiv 2020.
61. Zhang H, Kang Z, Gong H, Xu D, Wang J, Li Z, et al. The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes.
BioRxiv 2020; Inpress.
62. Zhou P, Yang X-L, Wang X-G, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin.
Nature 2020; 579:270–273.
63. Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus.
Nature 2003; 426:450–454.
64. Hoffmann M, Kleine-Weber H, Krüger N, Mueller MA, Drosten C, Pöhlmann S. The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells.
BioRxiv 2020.
65. Ouyang S. Cryo-electron microscopy structure of the SADS-CoV spike glycoprotein provides insights into an evolution of unique coronavirus spike proteins.
BioRxiv 2020.
66. Coutard B, Valle C, de Lamballerie X, Canard B, Seidah N, Decroly E. The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade.
Antiviral Res 2020; 176:104742.
67. Lu X, Shi Y, Gao F, Xiao H, Wang M, Qi J, Gao GF. Insights into avian influenza virus pathogenicity: the hemagglutinin precursor HA0 of subtype H16 has an alpha-helix structure in its cleavage site with inefficient HA1/HA2 cleavage.
J Virol 2012; 86:12861–12870.
68. Cui J, Huang W, Wu B, Jin J, Jing L, Shi WP, et al. N-glycosylation by N-acetylglucosaminyltransferase V enhances the interaction of CD147/basigin with integrin β1 and promotes HCC metastasis.
J Pathol 2018; 245:41–52.
69. Huang Q, Li J, Xing J, Li W, Li H, Ke X, et al. CD147 promotes reprogramming of glucose metabolism and cell proliferation in HCC cells by inhibiting the p53-dependent signaling pathway.
J Hepatol 2014; 61:859–866.
70. Lu M, Wu J, Hao ZW, Shang YK, Xu J, Nan G, et al. Basolateral CD147 induces hepatocyte polarity loss by E-cadherin ubiquitination and degradation in hepatocellular carcinoma progress.
Hepatology 2018; 68:317–332.
71. Chen Z, Mi L, Xu J, Yu J, Wang X, Jiang J, et al. Function of HAb18G/CD147 in invasion of host cells by severe acute respiratory syndrome coronavirus.
J Infect Dis 2005; 191:755–760.
72. Yurchenko V, Constant S, Bukrinsky M. Dealing with the family: CD147 interactions with cyclophilins.
Immunology 2006; 117:301–309.
73. Wang K, Chen W, Zhou Y-S, Lian J-Q, Zhang Z, Du P, et al. SARS-CoV-2 invades host cells via a novel route: CD147-spike protein.
bioRxiv 2020; In press.
74. Bian H, Zheng Z-H, Wei D, Zhang Z, Kang W-Z, Hao C-Q, et al. Meplazumab treats COVID-19 pneumonia: an open-labelled, concurrent controlled add-on clinical trial.
medRxiv 2020; In press.
75. Kowalczuk S, Broer A, Tietze N, Vanslambrouck JM, Rasko JE, Broer S. A protein complex in the brush-border membrane explains a Hartnup disorder allele.
FASEB J 2008; 22:2880–2887.
76. Seow HF, Bröer S, Bröer A, Bailey CG, Potter SJ, Cavanaugh JA, et al. Hartnup disorder is caused by mutations in the gene encoding the neutral amino acid transporter SLC6A19.
Nat Genet 2004; 36:1003–1007.
77. Kleta R, Romeo E, Ristic Z, Ohura T, Stuart C, Arcos-Burgos M, et al. Mutations in SLC6A19, encoding B0AT1, cause Hartnup disorder.
Nat Genet 2004; 36:999–1002.
78. Broer A, Klingel K, Kowalczuk S, Rasko JE, Cavanaugh J, Broer S. Molecular cloning of mouse amino acid transport system B.
J Biol Chem 2004; 279:24467–24476.
79. Zhao Y, Zhao Z, Wang Y, Zhou Y, Ma Y, Zuo W. Single-cell RNA expression profiling of ACE2, thereceptor of SARS-CoV-2.
bioRxiv 2020; In press.
80. Hamming I, Timens W, Bulthuis M, Lely A, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis.
J Pathol 2004; 203:631–637.
81. Wang C, Wang S, Li D, Zhao X, Han S, Wang T, et al. Lectin-like intestinal defensin inhibits 2019-nCoV spike binding to ACE2.
bioRxiv 2020; In press.
82. Glowacka I, Bertram S, Müller MA, Allen P, Soilleux E, Pfefferle S, et al. Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response.
J Virol 2011; 85:4122–4134.
83. Kawase M, Shirato K, van der Hoek L, Taguchi F, Matsuyama S. Simultaneous treatment of human bronchial epithelial cells with serine and cysteine protease inhibitors prevents severe acute respiratory syndrome coronavirus entry.
J Virol 2012; 86:6537–6545.
84. Zhou Y, Vedantham P, Lu K, Agudelo J, Carrion R Jr, Nunneley JW, et al. Protease inhibitors targeting coronavirus and filovirus entry.
Antiviral Res 2015; 116:76–84.
85. Perico L, Benigni A, Remuzzi G. Should COVID-19 concern nephrologists? Why and to what extent? the emerging impasse of angiotensin blockade.
Nephron 2020; 144:213–221.
86. Yu L, Yuan K, Phuong HTA, Park BM, Kim SH. Angiotensin-(1-5), an active mediator of renin-angiotensin system, stimulates ANP secretion via Mas receptor.
Peptides 2016; 86:33–41.
87. Zhang R, Pan Y, Fanelli V, Wu S, Luo AA, Islam D, et al. Mechanical stress and the induction of lung fibrosis via the midkine signaling pathway.
Am J Respir Crit Care Med 2015; 192:315–323.
88. Chan JF-W, Zhang AJ, Yuan S, Poon VK-M, Chan CC-S, Lee AC-Y, et al. Simulation of the clinical and pathological manifestations of Coronavirus Disease 2019 (COVID-19) in golden Syrian hamster model: implications for disease pathogenesis and transmissibility.
Clin Infect Dis 2020; In press.
89. Imai Y, Kuba K, Penninger JM. The discovery of angiotensin-converting enzyme 2 and its role in acute lung injury in mice.
Exp Physiol 2008; 93:543–548.
90. Colafella KMM, Uijl E, Danser J. Interference with the renin-angiotensin system (RAS): classical inhibitors and novel approaches. In: Reference module in biomedical sciences: encyclopedia of endocrine diseases: Elsevier; 2018.
91. Monteil V, Kwon H, Prado P, Hagelkrüys A, Wimmer RA, Stahl M, et al. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2.
Cell 2020; 181:905.e7–913.e7.
92. Khodarahmi R, Jalali A, Sobhani M. The active-site engineered ‘inactive hrsACE2’ could be considered as a safer therapeutic agent in the treatment of COVID-19: an opinion. OSF. 2020. In press.
