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Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein

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Suryadevara, Naveenchandra, Shrihari, Swathi, Gilchuk, Pavlo, VanBlargan, Laura A., Binshtein, Elad, Zost, Seth J., Nargi, Rachel S., Sutton, Rachel E., Winkler, Emma S., Chen, Elaine C., Fouch, Mallorie E., Davidson, Edgar, Doranz, Benjamin J., Chen, Rita E., Shi, Pei-Yong, Carnahan, Robert H., Thackray, Larissa B., Diamond, Michael S., Crowe, James E.·2021·Cell
DOI 10.1016/j.cell.2021.03.029

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Abstract

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.

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Metadata

Authors
Suryadevara, N., Shrihari, S., Gilchuk, P., VanBlargan, L. A., Binshtein, E., Zost, S. J., Nargi, R. S., Sutton, R. E., Winkler, E. S., Chen, E. C., Fouch, M. E., Davidson, E., Doranz, B. J., Chen, R. E., Shi, P.-Y., Carnahan, R. H., Thackray, L. B., Diamond, M. S., & Crowe, J. E.
Venue
Cell
Publisher
Elsevier BV
Published
2021-04
Volume
184
Issue
9
Pages
2316-2331.e15
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2021.03.029
OpenAlex
W3139036184
Cited by
362
References
36
FWCI
24.80
Type
journal article
Language
en
Open access
bronze
Licence
Funders
  • DARPA
  • NIAID DMID

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CoChat. (2026). Citation check: Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein. https://app.cochat.ai/papers/10.1016/j.cell.2021.03.029
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Suryadevara, N., Shrihari, S., Gilchuk, P., VanBlargan, L. A., Binshtein, E., Zost, S. J., Nargi, R. S., Sutton, R. E., Winkler, E. S., Chen, E. C., Fouch, M. E., Davidson, E., Doranz, B. J., Chen, R. E., Shi, P.-Y., Carnahan, R. H., Thackray, L. B., Diamond, M. S., & Crowe, J. E. (2021). Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein. Cell. https://doi.org/10.1016/j.cell.2021.03.029

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