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The COVID-19 pandemic has had an unprecedented health and economic impact and there are currently no approved therapies. We have isolated an antibody, EY6A, from an individual convalescing from COVID-19 and have shown that it neutralizes SARS-CoV-2 and cross-reacts with SARS-CoV-1. EY6A Fab binds the receptor binding domain (RBD) of the viral spike glycoprotein tightly (KD of 2 nM), and a 2.6-Å-resolution crystal structure of an RBD-EY6A Fab complex identifies the highly conserved epitope, away from the ACE2 receptor binding site. Residues within this footprint are key to stabilizing the pre-fusion spike. Cryo-EM analyses of the pre-fusion spike incubated with EY6A Fab reveal a complex of the intact spike trimer with three Fabs bound and two further multimeric forms comprising the destabilized spike attached to Fab. EY6A binds what is probably a major neutralizing epitope, making it a candidate therapeutic for COVID-19.

Original publication

DOI

10.1038/s41594-020-0480-y

Type

Journal article

Journal

Nat Struct Mol Biol

Publication Date

10/2020

Volume

27

Pages

950 - 958

Keywords

Adult, Angiotensin-Converting Enzyme 2, Animals, Antibodies, Neutralizing, Antibodies, Viral, Betacoronavirus, Binding Sites, COVID-19, Chlorocebus aethiops, Coronavirus Infections, Cross Reactions, Cryoelectron Microscopy, Crystallography, X-Ray, Epitopes, Humans, Immunoglobulin Fab Fragments, Male, Pandemics, Peptidyl-Dipeptidase A, Pneumonia, Viral, Protein Conformation, Protein Domains, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Vero Cells