Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged coronavirus that is responsible for the current pandemic of coronavirus disease 2019 (COVID-19), which has resulted in more than 3.7 million infections and 260,000 deaths as of 6 May 20201,2. Vaccine and therapeutic discovery efforts are paramount to curb the pandemic spread of ... this zoonotic virus. The SARS-CoV-2 spike (S) glycoprotein promotes entry into host cells and is the main target of neutralizing antibodies. Here we describe several monoclonal antibodies that target the S glycoprotein of SARS-CoV-2, which we identified from memory B cells of an individual who was infected with severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003. One antibody (named S309) potently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2, by engaging the receptor-binding domain of the S glycoprotein. Using cryo-electron microscopy and binding assays, we show that S309 recognizes an epitope containing a glycan that is conserved within the Sarbecovirus subgenus, without competing with receptor attachment. Antibody cocktails that include S309 in combination with other antibodies that we identified further enhanced SARS-CoV-2 neutralization, and may limit the emergence of neutralization-escape mutants. These results pave the way for using S309 and antibody cocktails containing S309 for prophylaxis in individuals at a high risk of exposure or as a post-exposure therapy to limit or treat severe disease.
Mesh Terms:
Angiotensin-Converting Enzyme 2, Animals, Antibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral, Antibody-Dependent Cell Cytotoxicity, B-Lymphocytes, Betacoronavirus, COVID-19, Chlorocebus aethiops, Coronavirus Infections, Cross Reactions, Cryoelectron Microscopy, Epitopes, B-Lymphocyte, HEK293 Cells, Humans, Immune Evasion, Immunoglobulin Fab Fragments, Immunologic Memory, Killer Cells, Natural, Models, Molecular, Neutralization Tests, Pandemics, Peptidyl-Dipeptidase A, Pneumonia, Viral, SARS-CoV-2, Severe Acute Respiratory Syndrome, Severe acute respiratory syndrome-related coronavirus, Spike Glycoprotein, Coronavirus, Vero Cells
Angiotensin-Converting Enzyme 2, Animals, Antibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral, Antibody-Dependent Cell Cytotoxicity, B-Lymphocytes, Betacoronavirus, COVID-19, Chlorocebus aethiops, Coronavirus Infections, Cross Reactions, Cryoelectron Microscopy, Epitopes, B-Lymphocyte, HEK293 Cells, Humans, Immune Evasion, Immunoglobulin Fab Fragments, Immunologic Memory, Killer Cells, Natural, Models, Molecular, Neutralization Tests, Pandemics, Peptidyl-Dipeptidase A, Pneumonia, Viral, SARS-CoV-2, Severe Acute Respiratory Syndrome, Severe acute respiratory syndrome-related coronavirus, Spike Glycoprotein, Coronavirus, Vero Cells
Nature
Date: Jul. 01, 2020
PubMed ID: 32422645
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