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

Hejun LiuIan A Wilson


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.


Dec 20, 1993·Journal of Molecular Biology·M C Lawrence, P M Colman
Mar 23, 2004·Nucleic Acids Research·Robert C Edgar
Jun 3, 2004·Genome Research·Gavin E CrooksSteven E Brenner
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
May 14, 2005·Journal of Structural Biology·Christian SulowayBridget Carragher
Aug 8, 2007·Journal of Molecular Biology·Evgeny Krissinel, Kim Henrick
Apr 11, 2008·The Journal of Biological Chemistry·Elizabeth M BadenJames R Thompson
Mar 6, 2009·Journal of Structural Biology·Gabriel C LanderBridget Carragher
Aug 1, 2007·Journal of Applied Crystallography·Airlie J McCoyRandy J Read
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Vincent B ChenDavid C Richardson
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Jun 5, 2010·PLoS Pathogens·Joshua S Klein, Pamela J Bjorkman
Jul 9, 2011·Science·Damian C EkiertJaap Goudsmit
Nov 25, 2011·Nature·Jason S McLellanPeter D Kwong
Oct 3, 2012·Proceedings of the National Academy of Sciences of the United States of America·Peter S LeeIan A Wilson
Nov 10, 2015·Nature Medicine·Vineet D MenacheryRalph S Baric
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor
Oct 4, 2017·Science·Rameshwar U KadamIan A Wilson
Feb 6, 2018·Nature Structural & Molecular Biology·Nicholas C Wu, Ian A Wilson
Jan 14, 2020·Journal of Molecular Biology·Junhua PanStephen C Harrison
Feb 23, 2020·Science·Daniel WrappJason S McLellan
Mar 11, 2020·Cell·Alexandra C WallsDavid Veesler
May 6, 2020·Science·Yasunori WatanabeMax Crispin
May 8, 2020·Proceedings of the National Academy of Sciences of the United States of America·Jian ShangFang Li
May 11, 2020·Current Opinion in Immunology·Andrew B Ward, Ian A Wilson

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Datasets Mentioned


Methods Mentioned

electron microscopy
size exclusion chromatography
affinity purification

Software Mentioned

UCSF Chimera

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