Affordable Access

deepdyve-link
Publisher Website

Cross-Neutralization of a SARS-CoV-2 Antibody to a Functionally Conserved Site Is Mediated by Avidity.

Authors
  • Liu, Hejun1
  • Wu, Nicholas C1
  • Yuan, Meng1
  • Bangaru, Sandhya1
  • Torres, Jonathan L1
  • Caniels, Tom G2
  • van Schooten, Jelle2
  • Zhu, Xueyong1
  • Lee, Chang-Chun D1
  • Brouwer, Philip J M2
  • van Gils, Marit J2
  • Sanders, Rogier W3
  • Ward, Andrew B4
  • Wilson, Ian A5
  • 1 Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • 2 Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. , (Netherlands)
  • 3 Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA. , (Netherlands)
  • 4 Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
  • 5 Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: [email protected]
Type
Published Article
Journal
Immunity
Publication Date
Dec 15, 2020
Volume
53
Issue
6
Identifiers
DOI: 10.1016/j.immuni.2020.10.023
PMID: 33242394
Source
Medline
Language
English
License
Unknown

Abstract

Most antibodies isolated from individuals with coronavirus disease 2019 (COVID-19) are specific to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, COVA1-16 is a relatively rare antibody that also cross-neutralizes SARS-CoV. Here, we determined a crystal structure of the COVA1-16 antibody fragment (Fab) with the SARS-CoV-2 receptor-binding domain (RBD) and negative-stain electron microscopy reconstructions with the spike glycoprotein trimer to elucidate the structural basis of its cross-reactivity. COVA1-16 binds a highly conserved epitope on the SARS-CoV-2 RBD, mainly through a long complementarity-determining region (CDR) H3, and competes with the angiotensin-converting enzyme 2 (ACE2) receptor because of steric hindrance rather than epitope overlap. COVA1-16 binds to a flexible up conformation of the RBD on the spike and relies on antibody avidity for neutralization. These findings, along with the structural and functional rationale for epitope conservation, provide insights for development of more universal SARS-like coronavirus vaccines and therapies. Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Report this publication

Statistics

Seen <100 times