The antigenic anatomy of SARS-CoV-2 receptor binding domain

Dejnirattisai, Wanwisa, Zhou, Daming, Ginn, Helen M., Duyvesteyn, Helen M.E., Supasa, Piyada, Case, James Brett, Zhao, Yuguang, Walter, Thomas S., Mentzer, Alexander J., Liu, Chang, and others. (2021) The antigenic anatomy of SARS-CoV-2 receptor binding domain. Cell, 184 . pp. 1-79. ISSN 0092-8674. E-ISSN 1097-4172. (doi:10.1016/j.cell.2021.02.032) (KAR id:86706)

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Official URL: https://doi.org/10.1016/j.cell.2021.02.032

Abstract

Antibodies are crucial to immune protection against SARS-CoV-2, with some in emergency use as therapeutics. Here we identify 377 human monoclonal antibodies (mAbs) recognizing the virus spike, and focus mainly on 80 that bind the receptor binding domain (RBD). We devise a competition data driven method to map RBD binding sites. We find that although antibody binding sites are widely dispersed, neutralizing antibody binding is focused, with nearly all highly inhibitory mAbs (IC50<0.1μg/ml) blocking receptor interaction, except for one that binds a unique epitope in the N-terminal domain. Many of these neutralizing mAbs use public V-genes and are close to germline. We dissect the structural basis of recognition for this large panel of antibodies through X-ray crystallography and cryo-electron microscopy of 19 Fab-antigen structures. We find novel binding modes for some potently inhibitory antibodies and demonstrate that strongly neutralizing mAbs protect, prophylactically or therapeutically, in animal models.

Item Type:	Article
DOI/Identification number:	10.1016/j.cell.2021.02.032
Subjects:	Q Science > QR Microbiology > QR355 Virology
Divisions:	Divisions > Division of Natural Sciences > Medway School of Pharmacy
Depositing User:	Nigel Temperton
Date Deposited:	21 Feb 2021 21:05 UTC
Last Modified:	04 Jul 2023 14:14 UTC
Resource URI:	https://kar.kent.ac.uk/id/eprint/86706 (The current URI for this page, for reference purposes)

University of Kent Author Information

Temperton, Nigel.

Creator's ORCID:	https://orcid.org/0000-0002-7978-3815
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