Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient

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.

Media Type:

Electronic Article

Year of Publication:

2020

Contained In:

Nature structural & molecular biology - Vol. 27, No. 10 (2020), p. 950-958

Language:

English

Contributors:

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
Huang, Kuan-Ying A

Links:

Volltext

Keywords:

Adult
Angiotensin converting enzyme 2
Animals
Antibodies, Neutralizing
Antibodies, Viral
Betacoronavirus
Binding Sites
Chlorocebus aethiops
Coronavirus Infections
Cross Reactions
Cryoelectron Microscopy
Crystallography, X-Ray
EC 3.4.15.1
EC 3.4.17.-
Epitopes
Humans
Immunoglobulin Fab Fragments
Journal Article
Male
Pandemics
Peptidyl-Dipeptidase A
Pneumonia, Viral
Protein Conformation
Protein Domains
Research Support, Non-U.S. Gov't
Spike Glycoprotein, Coronavirus
Spike protein, SARS-CoV-2
Vero Cells

Notes:

Date Completed 29.10.2020

Date Revised 29.10.2020

published: Print-Electronic

Citation Status MEDLINE

Copyright: From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Physical Description:

Online-Ressource

doi:

10.1038/s41594-020-0480-y

PMID:

32737466

PPN (Catalogue-ID):

NLM314056289