EMD-23154

Single-particle
25.0 Å
EMD-23154 Deposition: 17/12/2020
Map released: 27/01/2021
Last modified: 31/03/2021
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-23154

Negative stain EM map of SARS-CoV-2 spike protein (trimer) with Fab COV2-2489 (NTD)

EMD-23154

Single-particle
25.0 Å
EMD-23154 Deposition: 17/12/2020
Map released: 27/01/2021
Last modified: 31/03/2021
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
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
Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein.
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.