| Literature DB >> 32737466 |
Daming Zhou1, Helen M E Duyvesteyn1, Cheng-Pin Chen2, Yuguang Zhao1, Chung-Guei Huang3,4, Ting-Hua Chen5, Shin-Ru Shih3,4, Yi-Chun Lin6, Chien-Yu Cheng2, Shu-Hsing Cheng6, Yhu-Chering Huang7, Tzou-Yien Lin7, Che Ma5, Jiandong Huo1,8,9, Loic Carrique1, Tomas Malinauskas1, Reinis R Ruza1, Pranav N M Shah1, Tiong Kit Tan10, Pramila Rijal10,11, Robert F Donat10, Kerry Godwin12, Karen R Buttigieg12, Julia A Tree12, Julika Radecke13, Neil G Paterson13, Piyada Supasa14, Juthathip Mongkolsapaya14,15, Gavin R Screaton14, Miles W Carroll12,14, Javier Gilbert-Jaramillo16, Michael L Knight16, William James16, Raymond J Owens1,8,9, James H Naismith1,8,9, Alain R Townsend10,11, Elizabeth E Fry1, Jingshan Ren1, David I Stuart17,18,19, Kuan-Ying A Huang20,21.
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.Entities:
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Year: 2020 PMID： 32737466 DOI： 10.1038/s41594-020-0480-y
Source DB: PubMed Journal: Nat Struct Mol Biol ISSN： 1545-9985 Impact factor: 15.369