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

Immunity
Hejun LiuIan A Wilson

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.

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Citations

Feb 25, 2021·Science Immunology·Mrunal SakharkarLaura M Walker
Mar 7, 2021·Virology·James Brett CaseMichael S Diamond
Mar 14, 2021·Cell Reports·Chloe Rees-SpearLaura E McCoy
Mar 9, 2021·Nature·Pengfei WangDavid D Ho
May 7, 2021·The Journal of Biological Chemistry·Ian A Wilson, Robyn L Stanfield
May 15, 2021·Frontiers in Cell and Developmental Biology·Wenrui JiaZheng Zhou
May 11, 2021·Nature·Kevin O SaundersBarton F Haynes
Jun 1, 2021·Cell Reports Medicine·Andrea R ShiakolasIvelin S Georgiev
Jun 12, 2021·Biochemical and Biophysical Research Communications·Dongfu JinJian Sun

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Datasets Mentioned

BETA
MT599835
MT599919
QHD43416.1
ABF65836.1
the
QLR06866.1
BAB40370.1
AAP33697.1
and
MT449663.1

Methods Mentioned

BETA
electron microscopy
biosensor
PISA
size exclusion chromatography
X-ray
transfection
affinity purification
biosensors
Assay

Software Mentioned

PISA
ConSurf
HKL2000
nsEM
ExPASy
UCSF Chimera
Appion
ProtParam
MolProbity
COOT

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