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
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiotensin-Converting Enzyme 2
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Animals
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Betacoronavirus / drug effects*
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Betacoronavirus / metabolism
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Binding, Competitive / drug effects
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Cross Reactions
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Drug Design
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Humans
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Immunoglobulin Fc Fragments / chemistry*
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Immunoglobulin Fc Fragments / metabolism
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Immunoglobulin Fc Fragments / pharmacology
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Immunoglobulin G / chemistry*
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Immunoglobulin G / metabolism
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Immunoglobulin G / pharmacology
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In Vitro Techniques
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Inhibitory Concentration 50
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Membrane Fusion / drug effects
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Mice
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Mice, Inbred BALB C
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Mutation
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Neutralization Tests*
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Peptide Fragments / chemistry
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Peptide Fragments / genetics
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Peptide Fragments / metabolism
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Peptide Fragments / pharmacology
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Peptidyl-Dipeptidase A / chemistry*
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Peptidyl-Dipeptidase A / genetics
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Peptidyl-Dipeptidase A / pharmacokinetics
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Peptidyl-Dipeptidase A / pharmacology
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Protein Domains / genetics
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Protein Stability
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Receptors, Virus / antagonists & inhibitors
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Receptors, Virus / chemistry
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Receptors, Virus / genetics
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Receptors, Virus / metabolism
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Recombinant Fusion Proteins / chemistry*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / pharmacokinetics
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Recombinant Fusion Proteins / pharmacology*
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SARS-CoV-2
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Severe acute respiratory syndrome-related coronavirus / drug effects
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Severe acute respiratory syndrome-related coronavirus / metabolism
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Spike Glycoprotein, Coronavirus / antagonists & inhibitors*
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Spike Glycoprotein, Coronavirus / chemistry
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Spike Glycoprotein, Coronavirus / metabolism
Substances
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Immunoglobulin Fc Fragments
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Immunoglobulin G
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Peptide Fragments
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Receptors, Virus
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Recombinant Fusion Proteins
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Spike Glycoprotein, Coronavirus
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spike protein, SARS-CoV-2
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Peptidyl-Dipeptidase A
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ACE2 protein, human
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Ace2 protein, mouse
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Angiotensin-Converting Enzyme 2