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

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 CV...

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Bibliographic Details
Published in:Nature communications 2020-10, Vol.11 (1), p.5413-7, Article 5413
Main Authors: Hurlburt, Nicholas K., Seydoux, Emilie, Wan, Yu-Hsin, Edara, Venkata Viswanadh, Stuart, Andrew B., Feng, Junli, Suthar, Mehul S., McGuire, Andrew T., Stamatatos, Leonidas, Pancera, Marie
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Language:English
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Summary: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. Currently there is neither a vaccine nor an effective treatment strategy available for COVID19. Here, Hurlburt et al. provide the crystal structure of a patient-derived monoclonal antibody neutralizing SARS-CoV-2 via shedding of the S1 subunit and competing for the receptor binding domain.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-020-19231-9