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

被引：0

作者：

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

机构：

[1] University of Oxford,Division of Structural Biology, Nuffield Department of Medicine

[2] The Wellcome Centre for Human Genetics,Department of Infectious Diseases, Taoyuan General Hospital, Ministry of Health and Welfare

[3] Headington,Research Center for Emerging Viral Infections, College of Medicine

[4] Taoyuan,Department of Laboratory Medicine

[5] and National Yang-Ming University,Genomics Research Center

[6] Chang Gung University,Department of Infectious Diseases

[7] Chang Gung Memorial Hospital,Division of Pediatric Infectious Diseases, Department of Pediatrics

[8] Academia Sinica,Protein Production UK, Research Complex at Harwell

[9] Taoyuan General Hospital,MRC Human Immunology Unit

[10] Ministry of Health and Welfare,Centre for Translational Immunology

[11] Taoyuan,National Infection Service

[12] and Taipei Medical University,Diamond Light Source Ltd

[13] Chang Gung Memorial Hospital,Nuffield Department of Medicine, Wellcome Centre for Human Genetics

[14] The Rosalind Franklin Institute,Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine

[15] Harwell Campus,William Dunn School of Pathology

[16] Harwell Science & Innovation Campus,undefined

[17] Weatherall Institute of Molecular Medicine,undefined

[18] University of Oxford,undefined

[19] John Radcliffe Hospital,undefined

[20] Chinese Academy of Medical Sciences Oxford Institute,undefined

[21] University of Oxford,undefined

[22] Public Health England,undefined

[23] Porton Down,undefined

[24] Harwell Science & Innovation Campus,undefined

[25] University of Oxford,undefined

[26] Siriraj Hospital,undefined

[27] Mahidol University,undefined

[28] University of Oxford,undefined

来源：

Nature Structural & Molecular Biology | 2020年 / 27卷

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摘要：

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.

引用

页码：950 / 958

页数：8

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