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

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

Nature structural & molecular biology (2020-08-02)

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

PMID32737466

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.

MATERIALS

Product Number

Brand

Product Description

11484281001

Roche

BM Blue POD Substrate, soluble, solution (ready-to-use), suitable for ELISA, pkg of 100 mL