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

DOI: 10.1038/s41594-020-0480-y

Authors: Daming Zhou (The Wellcome Centre for Human Genetics, University of Oxford) , Helen M. E. Duyvesteyn (The Wellcome Centre for Human Genetics, University of Oxford) , Cheng-Pin Chen (Taoyuan General Hospital; National Yang-Ming University) , Chung-Guei Huang (Chang Gung University; Chang Gung Memorial Hospital) , Ting-Hua Chen (Academia Sinica) , Shin-Ru Shih (Chang Gung University; Chang Gung Memorial Hospital) , Yi-Chun Lin (Taoyuan General Hospital; Taipei Medical University) , Chien-Yu Cheng (Taoyuan General Hospital; National Yang-Ming University) , Shu-Hsing Cheng (Taoyuan General Hospital; Taipei Medical University) , Yhu-Chering Huang (Chang Gung Memorial Hospital) , Tzou-Yien Lin (Chang Gung Memorial Hospital) , Che Ma (Academia Sinica) , Jiandong Huo (The Wellcome Centre for Human Genetics, University of Oxford; The Rosalind Franklin Institute; Research Complex at Harwell) , Loic Carrique (The Wellcome Centre for Human Genetics, University of Oxford) , Tomas Malinauskas (The Wellcome Centre for Human Genetics, University of Oxford) , Reinis R. Ruza (The Wellcome Centre for Human Genetics, University of Oxford) , Pranav Shah (The Wellcome Centre for Human Genetics, University of Oxford) , Tiong Kit Tan (University of Oxford) , Pramila Rijal (University of Oxford) , Robert F. Donat (University of Oxford) , Kerry Godwin (Public Health England) , Karen R. Buttigieg (Public Health England) , Julia A. Tree (Public Health England) , Julika Radecke (Diamond Light Source) , Neil Paterson (Diamond Light Source) , Piyada Supasa (The Wellcome Centre for Human Genetics, University of Oxford) , Juthathip Mongkolsapaya (The Wellcome Centre for Human Genetics, University of Oxford; Mahidol University) , Gavin R. Screaton (The Wellcome Centre for Human Genetics, University of Oxford) , Miles W. Carroll (Public Health England; The Wellcome Centre for Human Genetics, University of Oxford) , Javier Gilbert-Jaramillo (University of Oxford) , Michael L. Knight (University of Oxford) , William James (University of Oxford) , Raymond J. Owens (The Wellcome Centre for Human Genetics, University of Oxford; The Rosalind Franklin Institute; Protein Production UK, Research Complex at Harwell) , James H. Naismith (The Wellcome Centre for Human Genetics, University of Oxford; The Rosalind Franklin Institute; Protein Production UK, Research Complex at Harwell) , Alain R. Townsend (University of Oxford) , Elizabeth E. Fry (The Wellcome Centre for Human Genetics, University of Oxford) , Yuguang Zhao (The Wellcome Centre for Human Genetics, University of Oxford) , Jingshan Ren (The Wellcome Centre for Human Genetics, University of Oxford) , David I. Stuart (The Wellcome Centre for Human Genetics, University of Oxford; Diamond Light Source) , Kuan-Ying A. Huang (Chang Gung University; Chang Gung Memorial Hospital)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Structural & Molecular Biology , VOL 20

State: Published (Approved)
Published: July 2020
Diamond Proposal Number(s): 19946 , 26983

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.

Journal Keywords: Biophysics; Cryoelectron microscopy; Diseases; Immunology; X-ray crystallography

Diamond Keywords: COVID-19; Viruses

Subject Areas: Biology and Bio-materials, Medicine

Diamond Offline Facilities: Electron Bio-Imaging Centre (eBIC)
Instruments: I03-Macromolecular Crystallography , Krios I-Titan Krios I at Diamond

Added On: 03/08/2020 14:09

Discipline Tags:

Pathogens Infectious Diseases Health & Wellbeing Structural biology Biophysics Drug Discovery Life Sciences & Biotech

Technical Tags:

Diffraction Microscopy Macromolecular Crystallography (MX) Electron Microscopy (EM) Cryo Electron Microscopy (Cryo EM)