Publication: Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike
Issued Date
2020-01-01
Resource Type
ISSN
19346069
19313128
19313128
Other identifier(s)
2-s2.0-85086783619
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Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Cell Host and Microbe. (2020)
Suggested Citation
Jiandong Huo, Yuguang Zhao, Jingshan Ren, Daming Zhou, Helen M.E. Duyvesteyn, Helen M. Ginn, Loic Carrique, Tomas Malinauskas, Reinis R. Ruza, Pranav N.M. Shah, Tiong Kit Tan, Pramila Rijal, Naomi Coombes, Kevin R. Bewley, Julia A. Tree, Julika Radecke, Neil G. Paterson, Piyasa Supasa, Juthathip Mongkolsapaya, Gavin R. Screaton, Miles Carroll, Alain Townsend, Elizabeth E. Fry, Raymond J. Owens, David I. Stuart Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike. Cell Host and Microbe. (2020). doi:10.1016/j.chom.2020.06.010 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/57987
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Title
Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike
Author(s)
Jiandong Huo
Yuguang Zhao
Jingshan Ren
Daming Zhou
Helen M.E. Duyvesteyn
Helen M. Ginn
Loic Carrique
Tomas Malinauskas
Reinis R. Ruza
Pranav N.M. Shah
Tiong Kit Tan
Pramila Rijal
Naomi Coombes
Kevin R. Bewley
Julia A. Tree
Julika Radecke
Neil G. Paterson
Piyasa Supasa
Juthathip Mongkolsapaya
Gavin R. Screaton
Miles Carroll
Alain Townsend
Elizabeth E. Fry
Raymond J. Owens
David I. Stuart
Yuguang Zhao
Jingshan Ren
Daming Zhou
Helen M.E. Duyvesteyn
Helen M. Ginn
Loic Carrique
Tomas Malinauskas
Reinis R. Ruza
Pranav N.M. Shah
Tiong Kit Tan
Pramila Rijal
Naomi Coombes
Kevin R. Bewley
Julia A. Tree
Julika Radecke
Neil G. Paterson
Piyasa Supasa
Juthathip Mongkolsapaya
Gavin R. Screaton
Miles Carroll
Alain Townsend
Elizabeth E. Fry
Raymond J. Owens
David I. Stuart
Other Contributor(s)
Public Health England
Diamond Light Source
The Wellcome Centre for Human Genetics
University of Oxford
Faculty of Medicine, Siriraj Hospital, Mahidol University
Nuffield Department of Medicine
MRC Weatherall Institute of Molecular Medicine
Rosalind Franklin Institute
INSTRUCT-ERIC
Research Complex at Harwell
Diamond Light Source
The Wellcome Centre for Human Genetics
University of Oxford
Faculty of Medicine, Siriraj Hospital, Mahidol University
Nuffield Department of Medicine
MRC Weatherall Institute of Molecular Medicine
Rosalind Franklin Institute
INSTRUCT-ERIC
Research Complex at Harwell
Abstract
© 2020 There are as yet no licensed therapeutics for the COVID-19 pandemic. The causal coronavirus (SARS-CoV-2) binds host cells via a trimeric spike whose receptor binding domain (RBD) recognizes angiotensin-converting enzyme 2, initiating conformational changes that drive membrane fusion. We find that the monoclonal antibody CR3022 binds the RBD tightly, neutralizing SARS-CoV-2, and report the crystal structure at 2.4 Å of the Fab/RBD complex. Some crystals are suitable for screening for entry-blocking inhibitors. The highly conserved, structure-stabilizing CR3022 epitope is inaccessible in the prefusion spike, suggesting that CR3022 binding facilitates conversion to the fusion-incompetent post-fusion state. Cryogenic electron microscopy (cryo-EM) analysis confirms that incubation of spike with CR3022 Fab leads to destruction of the prefusion trimer. Presentation of this cryptic epitope in an RBD-based vaccine might advantageously focus immune responses. Binders at this epitope could be useful therapeutically, possibly in synergy with an antibody that blocks receptor attachment.