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Structural basis for potent neutralization of SARS-CoV-2 and role of antibody affinity maturation.

ABSTRACT: SARS-CoV-2 is a betacoronavirus virus responsible for the COVID-19 pandemic. Here, we determine the X-ray crystal structure of a potent neutralizing monoclonal antibody, CV30, isolated from a patient infected with SARS-CoV-2, in complex with the receptor binding domain. The structure reveals that CV30 binds to an epitope that overlaps with the human ACE2 receptor binding motif providing a structural basis for its neutralization. CV30 also induces shedding of the S1 subunit, indicating an additional mechanism of neutralization. A germline reversion of CV30 results in a substantial reduction in both binding affinity and neutralization potential indicating the minimal somatic mutation is needed for potently neutralizing antibodies against SARS-CoV-2.

SUBMITTER: Hurlburt NK

PROVIDER: S-EPMC7591918 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Structural basis for potent neutralization of SARS-CoV-2 and role of antibody affinity maturation.

Hurlburt Nicholas K NK Seydoux Emilie E Wan Yu-Hsin YH Edara Venkata Viswanadh VV Stuart Andrew B AB Feng Junli J Suthar Mehul S MS McGuire Andrew T AT Stamatatos Leonidas L Pancera Marie M

Nature communications 20201027 1

SARS-CoV-2 is a betacoronavirus virus responsible for the COVID-19 pandemic. Here, we determine the X-ray crystal structure of a potent neutralizing monoclonal antibody, CV30, isolated from a patient infected with SARS-CoV-2, in complex with the receptor binding domain. The structure reveals that CV30 binds to an epitope that overlaps with the human ACE2 receptor binding motif providing a structural basis for its neutralization. CV30 also induces shedding of the S1 subunit, indicating an additio ...[more]

PMID: 33110068

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