Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike

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; Piyada Supasa; Juthathip Mongkolsapaya; Gavin R. Screaton; Miles Carroll; Alain Townsend; Elizabeth E. Fry; Raymond J. Owens; David I. Stuart

doi:10.1016/j.chom.2020.06.010

Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike

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
, Piyada Supasa
, Juthathip Mongkolsapaya
, Gavin R. Screaton

Miles Carroll, Alain Townsend, Elizabeth E. Fry, Raymond J. Owens, David I. Stuart

^*Corresponding author for this work

Countermeasures Development & Evaluation Project Staff

Research output: Contribution to journal › Article › peer-review

245 Citations (Scopus)

32 Downloads (Pure)

Abstract

Huo et al. find that the antibody CR3022 binds tightly to the receptor binding domain of the SARS-CoV-2 spike at a site different to that used by the receptor. CR3022 effectively neutralizes the virus, and cryo-EM reveals that it disrupts the spike. Such antibodies could have potential as COVID-19 therapeutics.

Original language	English
Pages (from-to)	445-454.e6
Journal	Cell Host and Microbe
Volume	28
Issue number	3
Early online date	19 Jun 2020
DOIs	https://doi.org/10.1016/j.chom.2020.06.010
Publication status	Published - 9 Sept 2020

Bibliographical note

Funding Information: This work was supported by a grant from the CAMS-Oxford Institute to D.I.S. E.E.F. H.M.E.D. and J. Ren are supported by the Wellcome Trust (101122/Z/13/Z); Y.Z. by Cancer Research UK (C375/A17721); and D.I.S. and E.E.F. by the UK Medical Research Council (MR/N00065X/1). J.H. is supported by a grant from the EPA Cephalosporin Fund. Protein Production UK (PPUK) is funded by the Rosalind Franklin Institute EPSRC grant no. EP/S025243/1. The National Institutes for Health Research Biomedical Research Centre Funding Scheme supports G.R.S. together with the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science (CIFMS) (grant number: 2018-I2M-2-002), which also supports D.I.S. G.R.S. is also supported as a Wellcome Trust Senior Investigator (grant 095541/A/11/Z). T.M. is supported by Cancer Research UK grants C20724/A14414 and C20724/A26752 to Christian Siebold. This is a contribution from the UK Instruct-ERIC Centre. The Wellcome Centre for Human Genetics is supported by the Wellcome Trust (grant 090532/Z/09/Z). The virus used for the neutralization assays was a gift from Julian Druce, Doherty Centre, Melbourne, Australia. We acknowledge Diamond Light Source for time on Beamline I03 under Proposal mx19946 and for electron microscope time at the UK national electron bio-imaging center (eBIC), proposal BI26983-2, both COVID-19 Rapid Access. Huge thanks to the teams, especially at the Diamond Light Source and Department of Structural Biology, Oxford University that have enabled work to continue during the pandemic. These authors contributed equally: Y. Zhao and J. Huo. J.H. and D.Z. performed interaction analyses. T.T. P.R. A.T. N.C. K.B. J.T. and M.C. prepared material for and executed neutralization assays. Y.Z. J.H. and J. Ren performed sample preparation for and executed crystallographic experiments and processed the data. N.G.P. assisted with X-ray diffraction data collection. H.G. and J. Ren refined the structures and together with E.E.F. and D.I.S. analyzed the results. G.R.S. J.M. and P.S. prepared the spike construct. L.C. helped performed cryo-EM data processing, T.M. R.R.R. and P.N.M.S. prepared the spike sample; H.M.E.D. performed cryo-EM sample preparation screening and processing; and J. Radecke performed cryo-EM data collection. E.E.F. J. Ren, Y.Z. and D.I.S. wrote the manuscript. All authors read and approved the manuscript. The authors declare no competing interests.

Open Access: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Publisher Copyright: © 2020 The Authors. Published by Elsevier Inc.

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, Piyada 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 & Microbe, Volume 28, Issue 3, 2020, Pages 445-454.e6, ISSN 1931-3128, https://doi.org/10.1016/j.chom.2020.06.010.
(https://www.sciencedirect.com/science/article/pii/S1931312820303516).

DOI: https://doi.org/10.1016/j.chom.2020.06.010

Keywords

CR3022
SARS-CoV-2
X-ray crystallography
antibody
cryo-electron microscopy
epitope
neutralization
receptor binding domain
spike
therapeutic

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Huo2020NeutralizationOfSARS-CoV-2ByDestructionOfThePrefusionSpikeCellHostMicrobeFinal published version, 4.71 MBLicence: CC BY

Cite this

Huo, J., Zhao, Y., Ren, J., Zhou, D., Duyvesteyn, H. M. E., Ginn, H. M., Carrique, L., Malinauskas, T., Ruza, R. R., Shah, P. N. M., Tan, T. K., Rijal, P., Coombes, N., Bewley, K. R., Tree, J. A., Radecke, J., Paterson, N. G., Supasa, P., Mongkolsapaya, J., ... Stuart, D. I. (2020). Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike. Cell Host and Microbe, 28(3), 445-454.e6. https://doi.org/10.1016/j.chom.2020.06.010

@article{61e5e2a8961b4d4590424f98bcf65a0a,

title = "Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike",

abstract = "Huo et al. find that the antibody CR3022 binds tightly to the receptor binding domain of the SARS-CoV-2 spike at a site different to that used by the receptor. CR3022 effectively neutralizes the virus, and cryo-EM reveals that it disrupts the spike. Such antibodies could have potential as COVID-19 therapeutics.",

keywords = "CR3022, SARS-CoV-2, X-ray crystallography, antibody, cryo-electron microscopy, epitope, neutralization, receptor binding domain, spike, therapeutic",

author = "Jiandong Huo and Yuguang Zhao and Jingshan Ren and Daming Zhou and Duyvesteyn, \{Helen M.E.\} and Ginn, \{Helen M.\} and Loic Carrique and Tomas Malinauskas and Ruza, \{Reinis R.\} and Shah, \{Pranav N.M.\} and Tan, \{Tiong Kit\} and Pramila Rijal and Naomi Coombes and Bewley, \{Kevin R.\} and Tree, \{Julia A.\} and Julika Radecke and Paterson, \{Neil G.\} and Piyada Supasa and Juthathip Mongkolsapaya and Screaton, \{Gavin R.\} and Miles Carroll and Alain Townsend and Fry, \{Elizabeth E.\} and Owens, \{Raymond J.\} and Stuart, \{David I.\}",

note = "Funding Information: This work was supported by a grant from the CAMS-Oxford Institute to D.I.S. E.E.F. H.M.E.D. and J. Ren are supported by the Wellcome Trust (101122/Z/13/Z); Y.Z. by Cancer Research UK (C375/A17721); and D.I.S. and E.E.F. by the UK Medical Research Council (MR/N00065X/1). J.H. is supported by a grant from the EPA Cephalosporin Fund. Protein Production UK (PPUK) is funded by the Rosalind Franklin Institute EPSRC grant no. EP/S025243/1. The National Institutes for Health Research Biomedical Research Centre Funding Scheme supports G.R.S. together with the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science (CIFMS) (grant number: 2018-I2M-2-002), which also supports D.I.S. G.R.S. is also supported as a Wellcome Trust Senior Investigator (grant 095541/A/11/Z). T.M. is supported by Cancer Research UK grants C20724/A14414 and C20724/A26752 to Christian Siebold. This is a contribution from the UK Instruct-ERIC Centre. The Wellcome Centre for Human Genetics is supported by the Wellcome Trust (grant 090532/Z/09/Z). The virus used for the neutralization assays was a gift from Julian Druce, Doherty Centre, Melbourne, Australia. We acknowledge Diamond Light Source for time on Beamline I03 under Proposal mx19946 and for electron microscope time at the UK national electron bio-imaging center (eBIC), proposal BI26983-2, both COVID-19 Rapid Access. Huge thanks to the teams, especially at the Diamond Light Source and Department of Structural Biology, Oxford University that have enabled work to continue during the pandemic. These authors contributed equally: Y. Zhao and J. Huo. J.H. and D.Z. performed interaction analyses. T.T. P.R. A.T. N.C. K.B. J.T. and M.C. prepared material for and executed neutralization assays. Y.Z. J.H. and J. Ren performed sample preparation for and executed crystallographic experiments and processed the data. N.G.P. assisted with X-ray diffraction data collection. H.G. and J. Ren refined the structures and together with E.E.F. and D.I.S. analyzed the results. G.R.S. J.M. and P.S. prepared the spike construct. L.C. helped performed cryo-EM data processing, T.M. R.R.R. and P.N.M.S. prepared the spike sample; H.M.E.D. performed cryo-EM sample preparation screening and processing; and J. Radecke performed cryo-EM data collection. E.E.F. J. Ren, Y.Z. and D.I.S. wrote the manuscript. All authors read and approved the manuscript. The authors declare no competing interests. Open Access: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) Publisher Copyright: {\textcopyright} 2020 The Authors. Published by Elsevier Inc. 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, Piyada 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 \& Microbe, Volume 28, Issue 3, 2020, Pages 445-454.e6, ISSN 1931-3128, https://doi.org/10.1016/j.chom.2020.06.010. (https://www.sciencedirect.com/science/article/pii/S1931312820303516). DOI: https://doi.org/10.1016/j.chom.2020.06.010",

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month = sep,

day = "9",

doi = "10.1016/j.chom.2020.06.010",

language = "English",

volume = "28",

pages = "445--454.e6",

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Huo, J, Zhao, Y, Ren, J, Zhou, D, Duyvesteyn, HME, Ginn, HM, Carrique, L, Malinauskas, T, Ruza, RR, Shah, PNM, Tan, TK, Rijal, P, Coombes, N , Bewley, KR , Tree, JA, Radecke, J, Paterson, NG, Supasa, P, Mongkolsapaya, J, Screaton, GR, Carroll, M, Townsend, A, Fry, EE, Owens, RJ & Stuart, DI 2020, 'Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike', Cell Host and Microbe, vol. 28, no. 3, pp. 445-454.e6. https://doi.org/10.1016/j.chom.2020.06.010

TY - JOUR

T1 - Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike

AU - Huo, Jiandong

AU - Zhao, Yuguang

AU - Ren, Jingshan

AU - Zhou, Daming

AU - Duyvesteyn, Helen M.E.

AU - Ginn, Helen M.

AU - Carrique, Loic

AU - Malinauskas, Tomas

AU - Ruza, Reinis R.

AU - Shah, Pranav N.M.

AU - Tan, Tiong Kit

AU - Rijal, Pramila

AU - Coombes, Naomi

AU - Bewley, Kevin R.

AU - Tree, Julia A.

AU - Radecke, Julika

AU - Paterson, Neil G.

AU - Supasa, Piyada

AU - Mongkolsapaya, Juthathip

AU - Screaton, Gavin R.

AU - Carroll, Miles

AU - Townsend, Alain

AU - Fry, Elizabeth E.

AU - Owens, Raymond J.

AU - Stuart, David I.

N1 - Funding Information: This work was supported by a grant from the CAMS-Oxford Institute to D.I.S. E.E.F. H.M.E.D. and J. Ren are supported by the Wellcome Trust (101122/Z/13/Z); Y.Z. by Cancer Research UK (C375/A17721); and D.I.S. and E.E.F. by the UK Medical Research Council (MR/N00065X/1). J.H. is supported by a grant from the EPA Cephalosporin Fund. Protein Production UK (PPUK) is funded by the Rosalind Franklin Institute EPSRC grant no. EP/S025243/1. The National Institutes for Health Research Biomedical Research Centre Funding Scheme supports G.R.S. together with the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science (CIFMS) (grant number: 2018-I2M-2-002), which also supports D.I.S. G.R.S. is also supported as a Wellcome Trust Senior Investigator (grant 095541/A/11/Z). T.M. is supported by Cancer Research UK grants C20724/A14414 and C20724/A26752 to Christian Siebold. This is a contribution from the UK Instruct-ERIC Centre. The Wellcome Centre for Human Genetics is supported by the Wellcome Trust (grant 090532/Z/09/Z). The virus used for the neutralization assays was a gift from Julian Druce, Doherty Centre, Melbourne, Australia. We acknowledge Diamond Light Source for time on Beamline I03 under Proposal mx19946 and for electron microscope time at the UK national electron bio-imaging center (eBIC), proposal BI26983-2, both COVID-19 Rapid Access. Huge thanks to the teams, especially at the Diamond Light Source and Department of Structural Biology, Oxford University that have enabled work to continue during the pandemic. These authors contributed equally: Y. Zhao and J. Huo. J.H. and D.Z. performed interaction analyses. T.T. P.R. A.T. N.C. K.B. J.T. and M.C. prepared material for and executed neutralization assays. Y.Z. J.H. and J. Ren performed sample preparation for and executed crystallographic experiments and processed the data. N.G.P. assisted with X-ray diffraction data collection. H.G. and J. Ren refined the structures and together with E.E.F. and D.I.S. analyzed the results. G.R.S. J.M. and P.S. prepared the spike construct. L.C. helped performed cryo-EM data processing, T.M. R.R.R. and P.N.M.S. prepared the spike sample; H.M.E.D. performed cryo-EM sample preparation screening and processing; and J. Radecke performed cryo-EM data collection. E.E.F. J. Ren, Y.Z. and D.I.S. wrote the manuscript. All authors read and approved the manuscript. The authors declare no competing interests. Open Access: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) Publisher Copyright: © 2020 The Authors. Published by Elsevier Inc. 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, Piyada 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 & Microbe, Volume 28, Issue 3, 2020, Pages 445-454.e6, ISSN 1931-3128, https://doi.org/10.1016/j.chom.2020.06.010. (https://www.sciencedirect.com/science/article/pii/S1931312820303516). DOI: https://doi.org/10.1016/j.chom.2020.06.010

PY - 2020/9/9

Y1 - 2020/9/9

N2 - Huo et al. find that the antibody CR3022 binds tightly to the receptor binding domain of the SARS-CoV-2 spike at a site different to that used by the receptor. CR3022 effectively neutralizes the virus, and cryo-EM reveals that it disrupts the spike. Such antibodies could have potential as COVID-19 therapeutics.

AB - Huo et al. find that the antibody CR3022 binds tightly to the receptor binding domain of the SARS-CoV-2 spike at a site different to that used by the receptor. CR3022 effectively neutralizes the virus, and cryo-EM reveals that it disrupts the spike. Such antibodies could have potential as COVID-19 therapeutics.

KW - CR3022

KW - SARS-CoV-2

KW - X-ray crystallography

KW - antibody

KW - cryo-electron microscopy

KW - epitope

KW - neutralization

KW - receptor binding domain

KW - spike

KW - therapeutic

UR - https://www.scopus.com/pages/publications/85086783619

U2 - 10.1016/j.chom.2020.06.010

DO - 10.1016/j.chom.2020.06.010

M3 - Article

C2 - 32585135

AN - SCOPUS:85086783619

SN - 1931-3128

VL - 28

SP - 445-454.e6

JO - Cell Host and Microbe

JF - Cell Host and Microbe

IS - 3

ER -

Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike

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Keywords

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