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.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:27

Enthalten in:

Nature structural & molecular biology - 27(2020), 10 vom: 14. Okt., Seite 950-958

Sprache:

Englisch

Beteiligte Personen:

Zhou, Daming [VerfasserIn]
Duyvesteyn, Helen M E [VerfasserIn]
Chen, Cheng-Pin [VerfasserIn]
Huang, Chung-Guei [VerfasserIn]
Chen, Ting-Hua [VerfasserIn]
Shih, Shin-Ru [VerfasserIn]
Lin, Yi-Chun [VerfasserIn]
Cheng, Chien-Yu [VerfasserIn]
Cheng, Shu-Hsing [VerfasserIn]
Huang, Yhu-Chering [VerfasserIn]
Lin, Tzou-Yien [VerfasserIn]
Ma, Che [VerfasserIn]
Huo, Jiandong [VerfasserIn]
Carrique, Loic [VerfasserIn]
Malinauskas, Tomas [VerfasserIn]
Ruza, Reinis R [VerfasserIn]
Shah, Pranav N M [VerfasserIn]
Tan, Tiong Kit [VerfasserIn]
Rijal, Pramila [VerfasserIn]
Donat, Robert F [VerfasserIn]
Godwin, Kerry [VerfasserIn]
Buttigieg, Karen R [VerfasserIn]
Tree, Julia A [VerfasserIn]
Radecke, Julika [VerfasserIn]
Paterson, Neil G [VerfasserIn]
Supasa, Piyada [VerfasserIn]
Mongkolsapaya, Juthathip [VerfasserIn]
Screaton, Gavin R [VerfasserIn]
Carroll, Miles W [VerfasserIn]
Gilbert-Jaramillo, Javier [VerfasserIn]
Knight, Michael L [VerfasserIn]
James, William [VerfasserIn]
Owens, Raymond J [VerfasserIn]
Naismith, James H [VerfasserIn]
Townsend, Alain R [VerfasserIn]
Fry, Elizabeth E [VerfasserIn]
Zhao, Yuguang [VerfasserIn]
Ren, Jingshan [VerfasserIn]
Stuart, David I [VerfasserIn]
Huang, Kuan-Ying A [VerfasserIn]

Links:

Volltext

Themen:

ACE2 protein, human
Angiotensin-Converting Enzyme 2
Antibodies, Neutralizing
Antibodies, Viral
EC 3.4.15.1
EC 3.4.17.23
Epitopes
Immunoglobulin Fab Fragments
Journal Article
Peptidyl-Dipeptidase A
Research Support, Non-U.S. Gov't
Spike Glycoprotein, Coronavirus
Spike protein, SARS-CoV-2

Anmerkungen:

Date Completed 29.10.2020

Date Revised 20.03.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1038/s41594-020-0480-y

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM313129428