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

• Published in: Nature structural & molecular biology Vol. 27; no. 10; pp. 950 - 958
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-10-2020
• Subjects: 101/1; 101/28; 631/250; 631/535/1258/1259; 631/535/1266; 631/57; 692/699; 82/103; 9/10; Adult; Angiotensin-Converting Enzyme 2; Animals; Antibodies, Neutralizing - immunology; Antibodies, Viral - chemistry; Antibodies, Viral - immunology; Antibodies, Viral - metabolism; Betacoronavirus - chemistry; Betacoronavirus - immunology; Betacoronavirus - metabolism; Binding Sites; Biochemistry; Biological Microscopy; Biomedical and Life Sciences; Chlorocebus aethiops; Coronavirus Infections - immunology; COVID-19; Cross Reactions; Cryoelectron Microscopy; Crystallography, X-Ray; Epitopes; Humans; Immunoglobulin Fab Fragments - chemistry; Immunoglobulin Fab Fragments - metabolism; Life Sciences; Male; Membrane Biology; Pandemics; Peptidyl-Dipeptidase A - metabolism; Pneumonia, Viral - immunology; Protein Conformation; Protein Domains; Protein Structure; SARS-CoV-2; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - immunology; Spike Glycoprotein, Coronavirus - metabolism; Vero Cells
• ISSN: 1545-9993; 1545-9985
• DOI: 10.1038/s41594-020-0480-y

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 (
K
D
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.
EY6A, a neutralizing antibody isolated from a patient convalescing from COVID-19, binds the receptor binding domain of the SARS-CoV-2 spike glycoprotein with high affinity, at a location away from the binding site for the ACE2 receptor, similar to the one recognized by CR3022.