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

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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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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591918/
https://www.ncbi.nlm.nih.gov/pubmed/33110068
http://dx.doi.org/10.1038/s41467-020-19231-9
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author 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
author_facet 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
author_sort Hurlburt, Nicholas K.
collection PubMed
description 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.
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spelling pubmed-75919182020-11-10 Structural basis for potent neutralization of SARS-CoV-2 and role of antibody affinity maturation 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 Nat Commun Article 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. Nature Publishing Group UK 2020-10-27 /pmc/articles/PMC7591918/ /pubmed/33110068 http://dx.doi.org/10.1038/s41467-020-19231-9 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
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
Structural basis for potent neutralization of SARS-CoV-2 and role of antibody affinity maturation
title Structural basis for potent neutralization of SARS-CoV-2 and role of antibody affinity maturation
title_full Structural basis for potent neutralization of SARS-CoV-2 and role of antibody affinity maturation
title_fullStr Structural basis for potent neutralization of SARS-CoV-2 and role of antibody affinity maturation
title_full_unstemmed Structural basis for potent neutralization of SARS-CoV-2 and role of antibody affinity maturation
title_short Structural basis for potent neutralization of SARS-CoV-2 and role of antibody affinity maturation
title_sort structural basis for potent neutralization of sars-cov-2 and role of antibody affinity maturation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591918/
https://www.ncbi.nlm.nih.gov/pubmed/33110068
http://dx.doi.org/10.1038/s41467-020-19231-9
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