Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient
pmid: 32737466
Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient
AbstractThe COVID-19 pandemic has had unprecedented health and economic impact, but currently there are no approved therapies. We have isolated an antibody, EY6A, from a late-stage COVID-19 patient and show it neutralises SARS-CoV-2 and cross-reacts with SARS-CoV-1. EY6A Fab binds tightly (KDof 2 nM) the receptor binding domain (RBD) of the viral Spike glycoprotein and a 2.6Å crystal structure of an RBD/EY6A Fab complex identifies the highly conserved epitope, away from the ACE2 receptor binding site. Residues of this epitope are key to stabilising the pre-fusion Spike. Cryo-EM analyses of the pre-fusion Spike incubated with EY6A Fab reveal a complex of the intact trimer with three Fabs bound and two further multimeric forms comprising destabilized Spike attached to Fab. EY6A binds what is probably a major neutralising epitope, making it a candidate therapeutic for COVID-19.
- University of Oxford, Nuffield Department of Medicine United Kingdom
- Academia Sinica Taiwan
- MRC Human Immunology Unit United Kingdom
- Siriraj Hospital Thailand
- Memorial Hospital of South Bend United States
Adult, Male, Pneumonia, Viral, Cross Reactions, Peptidyl-Dipeptidase A, Antibodies, Viral, Crystallography, X-Ray, Betacoronavirus, Epitopes, Immunoglobulin Fab Fragments, Structural Biology, Chlorocebus aethiops, Animals, Humans, Molecular Biology, Pandemics, Binding Sites, Cryoelectron Microscopy, COVID-19, Antibodies, Neutralizing, Angiotensin-Converting Enzyme 2, Coronavirus Infections
Adult, Male, Pneumonia, Viral, Cross Reactions, Peptidyl-Dipeptidase A, Antibodies, Viral, Crystallography, X-Ray, Betacoronavirus, Epitopes, Immunoglobulin Fab Fragments, Structural Biology, Chlorocebus aethiops, Animals, Humans, Molecular Biology, Pandemics, Binding Sites, Cryoelectron Microscopy, COVID-19, Antibodies, Neutralizing, Angiotensin-Converting Enzyme 2, Coronavirus Infections
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