Publication:
The antigenic anatomy of SARS-CoV-2 receptor binding domain

1

Issued Date

2021-04-15

Resource Type

Article

ISSN

10974172
00928674

DOI

10.1016/j.cell.2021.02.032

Other identifier(s)

2-s2.0-85102643098

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

Cell. Vol.184, No.8 (2021), 2183-2200.e22

Suggested Citation

Wanwisa Dejnirattisai, Daming Zhou, Helen M. Ginn, Helen M.E. Duyvesteyn, Piyada Supasa, James Brett Case, Yuguang Zhao, Thomas S. Walter, Alexander J. Mentzer, Chang Liu, Beibei Wang, Guido C. Paesen, Jose Slon-Campos, César López-Camacho, Natasha M. Kafai, Adam L. Bailey, Rita E. Chen, Baoling Ying, Craig Thompson, Jai Bolton, Alex Fyfe, Sunetra Gupta, Tiong Kit Tan, Javier Gilbert-Jaramillo, William James, Michael Knight, Miles W. Carroll, Donal Skelly, Christina Dold, Yanchun Peng, Robert Levin, Tao Dong, Andrew J. Pollard, Julian C. Knight, Paul Klenerman, Nigel Temperton, David R. Hall, Mark A. Williams, Neil G. Paterson, Felicity K.R. Bertram, C. Alistair Siebert, Daniel K. Clare, Andrew Howe, Julika Radecke, Yun Song, Alain R. Townsend, Kuan Ying A. Huang, Elizabeth E. Fry, Juthathip Mongkolsapaya, Michael S. Diamond, Jingshan Ren, David I. Stuart, Gavin R. Screaton The antigenic anatomy of SARS-CoV-2 receptor binding domain. Cell. Vol.184, No.8 (2021), 2183-2200.e22. doi:10.1016/j.cell.2021.02.032 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/76209

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Title

The antigenic anatomy of SARS-CoV-2 receptor binding domain

Author(s)

Wanwisa Dejnirattisai
 Daming Zhou
 Helen M. Ginn
 Helen M.E. Duyvesteyn
 Piyada Supasa
 James Brett Case
 Yuguang Zhao
 Thomas S. Walter
 Alexander J. Mentzer
 Chang Liu
 Beibei Wang
 Guido C. Paesen
 Jose Slon-Campos
 César López-Camacho
 Natasha M. Kafai
 Adam L. Bailey
 Rita E. Chen
 Baoling Ying
 Craig Thompson
 Jai Bolton
 Alex Fyfe
 Sunetra Gupta
 Tiong Kit Tan
 Javier Gilbert-Jaramillo
 William James
 Michael Knight
 Miles W. Carroll
 Donal Skelly
 Christina Dold
 Yanchun Peng
 Robert Levin
 Tao Dong
 Andrew J. Pollard
 Julian C. Knight
 Paul Klenerman
 Nigel Temperton
 David R. Hall
 Mark A. Williams
 Neil G. Paterson
 Felicity K.R. Bertram
 C. Alistair Siebert
 Daniel K. Clare
 Andrew Howe
 Julika Radecke
 Yun Song
 Alain R. Townsend
 Kuan Ying A. Huang
 Elizabeth E. Fry
 Juthathip Mongkolsapaya
 Michael S. Diamond
 Jingshan Ren
 David I. Stuart
 Gavin R. Screaton

Other Contributor(s)

NIHR Oxford Biomedical Research Centre
 Oxford University Hospitals NHS Foundation Trust
 Public Health England
 Diamond Light Source
 Chang Gung University College of Medicine
 Chang Gung Memorial Hospital
 Worthing Hospital
 University of Oxford
 Washington University School of Medicine in St. Louis
 Sir William Dunn School of Pathology
 Faculty of Medicine Siriraj Hospital, Mahidol University
 University of Kent
 Nuffield Department of Medicine
 University of Oxford Medical Sciences Division
 Instruct-ERIC

Abstract

Antibodies are crucial to immune protection against SARS-CoV-2, with some in emergency use as therapeutics. Here, we identify 377 human monoclonal antibodies (mAbs) recognizing the virus spike and focus mainly on 80 that bind the receptor binding domain (RBD). We devise a competition data-driven method to map RBD binding sites. We find that although antibody binding sites are widely dispersed, neutralizing antibody binding is focused, with nearly all highly inhibitory mAbs (IC50 < 0.1 μg/mL) blocking receptor interaction, except for one that binds a unique epitope in the N-terminal domain. Many of these neutralizing mAbs use public V-genes and are close to germline. We dissect the structural basis of recognition for this large panel of antibodies through X-ray crystallography and cryoelectron microscopy of 19 Fab-antigen structures. We find novel binding modes for some potently inhibitory antibodies and demonstrate that strongly neutralizing mAbs protect, prophylactically or therapeutically, in animal models.

Keyword(s)

Biochemistry, Genetics and Molecular Biology

Availability

URI

https://repository.li.mahidol.ac.th/handle/123456789/76209

Collections

Scopus 2021