EMD-23154
Negative stain EM map of SARS-CoV-2 spike protein (trimer) with Fab COV2-2489 (NTD)
EMD-23154
Single-particle25.0 Å
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Map released: 27/01/2021
Last modified: 31/03/2021
Sample Organism:
Severe acute respiratory syndrome coronavirus 2,
Homo sapiens
Sample: SARS-COV-2 spike protein (trimer) with Fab COV2-2489
Deposition Authors: Binshtein E, Crowe JE
Sample: SARS-COV-2 spike protein (trimer) with Fab COV2-2489
Deposition Authors: Binshtein E, Crowe JE
Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein.
Suryadevara N,
Shrihari S,
Gilchuk P,
VanBlargan LA,
Binshtein E,
Zost SJ,
Nargi RS,
Sutton RE,
Winkler ES,
Chen EC,
Fouch ME,
Davidson E,
Doranz BJ,
Carnahan RH,
Thackray LB,
Diamond MS,
Crowe JE
(2021) bioRxiv
(2021) bioRxiv
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.
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.
Secondary citations:
- Suryadevara N, Shrihari S, Gilchuk P, VanBlargan LA, Binshtein E, Zost SJ, Nargi RS, Sutton RE, Winkler ES, Chen EC, Fouch ME, Davidson E, Doranz BJ, Chen RE, Shi PY, Carnahan RH, Thackray LB, Diamond MS & Crowe Jr JE. (2021) Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein. Cell,
- Suryadevara N, Shrihari S, Gilchuk P, VanBlargan LA, Binshtein E, Zost SJ, Nargi RS, Sutton RE, Winkler ES, Chen EC, Fouch ME, Davidson E, Doranz BJ, Carnahan RH, Thackray LB, Diamond MS & Crowe JE. (2021) Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein. bioRxiv,