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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

88 Citations (Scopus)

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 languageEnglish
Pages (from-to)445-454.e6
JournalCell Host and Microbe
Volume28
Issue number3
DOIs
Publication statusPublished - 9 Sep 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.

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.

Publisher Copyright:
© 2020 The Authors

Keywords

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

Fingerprint

Dive into the research topics of 'Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike'. Together they form a unique fingerprint.

Cite this