Abstract
SARS-CoV-2 is a betacoronavirus virus responsible for the COVID-19 pandemic. Here, we determine the X-ray crystal structure of a potent neutralizing monoclonal antibody, CV30, isolated from a patient infected with SARS-CoV-2, in complex with the receptor binding domain. The structure reveals that CV30 binds to an epitope that overlaps with the human ACE2 receptor binding motif providing a structural basis for its neutralization. CV30 also induces shedding of the S1 subunit, indicating an additional mechanism of neutralization. A germline reversion of CV30 results in a substantial reduction in both binding affinity and neutralization potential indicating the minimal somatic mutation is needed for potently neutralizing antibodies against SARS-CoV-2.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Angiotensin-Converting Enzyme 2
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Antibodies, Blocking / chemistry
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Antibodies, Blocking / immunology
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Antibodies, Monoclonal / chemistry
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Antibodies, Monoclonal / immunology
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Antibodies, Neutralizing / chemistry*
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Antibodies, Neutralizing / immunology*
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Antibody Affinity*
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Betacoronavirus / immunology*
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COVID-19
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Coronavirus Infections / immunology
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Crystallography, X-Ray
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Epitopes, B-Lymphocyte
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HEK293 Cells
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Humans
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Inhibitory Concentration 50
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Models, Molecular
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Pandemics
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Peptidyl-Dipeptidase A / chemistry
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Peptidyl-Dipeptidase A / metabolism
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Pneumonia, Viral / immunology
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Protein Interaction Domains and Motifs
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Protein Subunits
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SARS-CoV-2
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Somatic Hypermutation, Immunoglobulin
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Spike Glycoprotein, Coronavirus / chemistry
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Spike Glycoprotein, Coronavirus / immunology
Substances
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Antibodies, Blocking
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Antibodies, Monoclonal
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Antibodies, Neutralizing
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Epitopes, B-Lymphocyte
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Protein Subunits
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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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Angiotensin-Converting Enzyme 2