Key result
Monoclonal antibodies COV2-2676 and COV2-2489 potently neutralize SARS-CoV-2 and protect mice from infection.
Why the study?
Most human monoclonal antibodies neutralizing SARS-CoV-2 target the spike protein receptor-binding domain, but the role and characteristics of antibodies targeting the N-terminal domain were less defined.
Natural infection induces a subset of potent NTD-specific mAbs that leverage neutralizing and Fc-mediated activities to protect against SARS-CoV-2 infection.
Answers are grounded in this paper and cite their sources.
NTD-neutralizing mAbs may expand therapeutic options beyond RBD; leaves open clinical translation pending further validation.
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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Suryadevara et al. (2021) studied SARS-CoV-2 infection. COV2-2676 and COV2-2489 vs. Isotype control mAb DENV-2D22 was evaluated on In vivo protection against SARS-CoV-2 challenge (weight loss and viral burden). COV2-2676 and COV2-2489, human monoclonal antibodies targeting the N-terminal domain of the SARS-CoV-2 spike protein, potently neutralized the virus and protected mice from infection and weight loss.
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