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TitleNeutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein.
Journal, issue, pagesbioRxiv, Year 2021
Publish dateJan 20, 2021
AuthorsNaveenchandra Suryadevara / Swathi Shrihari / Pavlo Gilchuk / Laura A VanBlargan / Elad Binshtein / Seth J Zost / Rachel S Nargi / Rachel E Sutton / Emma S Winkler / Elaine C Chen / Mallorie E Fouch / Edgar Davidson / Benjamin J Doranz / Robert H Carnahan / Larissa B Thackray / Michael S Diamond / James E Crowe
PubMed AbstractMost human monoclonal antibodies (mAbs) neutralizing SARS-CoV-2 recognize the spike (S) protein receptor-binding domain and block virus interactions with the cellular receptor angiotensin-converting ...Most human monoclonal antibodies (mAbs) neutralizing SARS-CoV-2 recognize the spike (S) protein receptor-binding domain and block virus interactions with the cellular receptor angiotensin-converting enzyme 2. We describe a panel of human mAbs binding to diverse epitopes on the N-terminal domain (NTD) of S protein from SARS-CoV-2 convalescent donors and found a minority of these possessed neutralizing activity. Two mAbs (COV2-2676 and COV2-2489) inhibited infection of authentic SARS-CoV-2 and recombinant VSV/SARS-CoV-2 viruses. We mapped their binding epitopes by alanine-scanning mutagenesis and selection of functional SARS-CoV-2 S neutralization escape variants. Mechanistic studies showed that these antibodies neutralize in part by inhibiting a post-attachment step in the infection cycle. COV2-2676 and COV2-2489 offered protection either as prophylaxis or therapy, and Fc effector functions were required for optimal protection. Thus, natural infection induces a subset of potent NTD-specific mAbs that leverage neutralizing and Fc-mediated activities to protect against SARS-CoV-2 infection using multiple functional attributes.
External linksbioRxiv / PubMed:33501445 / PubMed Central
MethodsEM (single particle)
Resolution21.0 - 25.0 Å
Structure data

EMDB-23154:
Negative stain EM map of SARS-CoV-2 spike protein (trimer) with Fab COV2-2489 (NTD)
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-23155:
Negative stain EM map of SARS-CoV-2 spike protein (trimer) with Fab COV2-2676 (NTD)
Method: EM (single particle) / Resolution: 21.0 Å

Source
  • Severe acute respiratory syndrome coronavirus 2
  • Homo sapiens (human)

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