Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, at the end of 2019, and there are currently no specific antiviral treatments or vaccines available. SARS-CoV-2 has been shown to use the same cell entry receptor as SARS-CoV, angiotensin-converting enzyme 2 (ACE2). In this report, we generate a recombinant protein by connecting the extracellular domain of human ACE2 to the Fc region of the human immunoglobulin IgG1. A fusion protein containing an ACE2 mutant with low catalytic activity is also used in this study. The fusion proteins are then characterized. Both fusion proteins have a high binding affinity for the receptor-binding domains of SARS-CoV and SARS-CoV-2 and exhibit desirable pharmacological properties in mice. Moreover, the fusion proteins neutralize virus pseudotyped with SARS-CoV or SARS-CoV-2 spike proteins in vitro. As these fusion proteins exhibit cross-reactivity against coronaviruses, they have potential applications in the diagnosis, prophylaxis, and treatment of SARS-CoV-2.
Publication types
- Research Support, Non-U.S. Gov't
MeSH terms
- Angiotensin-Converting Enzyme 2
- Animals
- Betacoronavirus / drug effects*
- Betacoronavirus / metabolism
- Binding, Competitive / drug effects
- Cross Reactions
- Drug Design
- Humans
- Immunoglobulin Fc Fragments / chemistry*
- Immunoglobulin Fc Fragments / metabolism
- Immunoglobulin Fc Fragments / pharmacology
- Immunoglobulin G / chemistry*
- Immunoglobulin G / metabolism
- Immunoglobulin G / pharmacology
- In Vitro Techniques
- Inhibitory Concentration 50
- Membrane Fusion / drug effects
- Mice
- Mice, Inbred BALB C
- Mutation
- Neutralization Tests*
- Peptide Fragments / chemistry
- Peptide Fragments / genetics
- Peptide Fragments / metabolism
- Peptide Fragments / pharmacology
- Peptidyl-Dipeptidase A / chemistry*
- Peptidyl-Dipeptidase A / genetics
- Peptidyl-Dipeptidase A / pharmacokinetics
- Peptidyl-Dipeptidase A / pharmacology
- Protein Domains / genetics
- Protein Stability
- Receptors, Virus / antagonists & inhibitors
- Receptors, Virus / chemistry
- Receptors, Virus / genetics
- Receptors, Virus / metabolism
- Recombinant Fusion Proteins / chemistry*
- Recombinant Fusion Proteins / genetics
- Recombinant Fusion Proteins / pharmacokinetics
- Recombinant Fusion Proteins / pharmacology*
- SARS-CoV-2
- Severe acute respiratory syndrome-related coronavirus / drug effects
- Severe acute respiratory syndrome-related coronavirus / metabolism
- Spike Glycoprotein, Coronavirus / antagonists & inhibitors*
- Spike Glycoprotein, Coronavirus / chemistry
- Spike Glycoprotein, Coronavirus / metabolism
Substances
- Immunoglobulin Fc Fragments
- Immunoglobulin G
- Peptide Fragments
- Receptors, Virus
- Recombinant Fusion Proteins
- Spike Glycoprotein, Coronavirus
- spike protein, SARS-CoV-2
- Peptidyl-Dipeptidase A
- ACE2 protein, human
- Ace2 protein, mouse
- Angiotensin-Converting Enzyme 2