Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient
Journal
Nature Structural and Molecular Biology
Journal Volume
27
Journal Issue
10
Pages
950
Date Issued
2020-10-01
Author(s)
Zhou, Daming
Duyvesteyn, Helen M.E.
Chen, Cheng Pin
Huang, Chung Guei
Chen, Ting Hua
Shih, Shin Ru
Lin, Yi Chun
Cheng, Chien Yu
Cheng, Shu Hsing
Huang, Yhu Chering
Lin, Tzou Yien
Ma, Che
Huo, Jiandong
Carrique, Loic
Malinauskas, Tomas
Ruza, Reinis R.
Shah, Pranav N.M.
Tan, Tiong Kit
Rijal, Pramila
Donat, Robert F.
Godwin, Kerry
Buttigieg, Karen R.
Tree, Julia A.
Radecke, Julika
Paterson, Neil G.
Supasa, Piyada
Mongkolsapaya, Juthathip
Screaton, Gavin R.
Carroll, Miles W.
Gilbert-Jaramillo, Javier
Knight, Michael L.
James, William
Owens, Raymond J.
Naismith, James H.
Townsend, Alain R.
Fry, Elizabeth E.
Zhao, Yuguang
Ren, Jingshan
Stuart, David I.
Abstract
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.
Subjects
NANOLITRE CRYSTALLIZATION EXPERIMENTS; CRYO-EM STRUCTURE; SARS CORONAVIRUS; POTENT NEUTRALIZATION; PROTEIN; SPIKE
Publisher
NATURE PORTFOLIO
Type
journal article
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Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient
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