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SARS-CoV-2 variants of concern: spike protein mutational analysis and epitope for broad neutralization
Mutations in the spike glycoproteins of SARS-CoV-2 variants of concern have independently been shown to enhance aspects of spike protein fitness. Here, we describe an antibody fragment (V(H) ab6) that neutralizes all major variants including the recently emerged BA.1 and BA.2 Omicron subvariants, wi...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9388680/ https://www.ncbi.nlm.nih.gov/pubmed/35982054 http://dx.doi.org/10.1038/s41467-022-32262-8 |
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author | Mannar, Dhiraj Saville, James W. Sun, Zehua Zhu, Xing Marti, Michelle M. Srivastava, Shanti S. Berezuk, Alison M. Zhou, Steven Tuttle, Katharine S. Sobolewski, Michele D. Kim, Andrew Treat, Benjamin R. Da Silva Castanha, Priscila Mayrelle Jacobs, Jana L. Barratt-Boyes, Simon M. Mellors, John W. Dimitrov, Dimiter S. Li, Wei Subramaniam, Sriram |
author_facet | Mannar, Dhiraj Saville, James W. Sun, Zehua Zhu, Xing Marti, Michelle M. Srivastava, Shanti S. Berezuk, Alison M. Zhou, Steven Tuttle, Katharine S. Sobolewski, Michele D. Kim, Andrew Treat, Benjamin R. Da Silva Castanha, Priscila Mayrelle Jacobs, Jana L. Barratt-Boyes, Simon M. Mellors, John W. Dimitrov, Dimiter S. Li, Wei Subramaniam, Sriram |
author_sort | Mannar, Dhiraj |
collection | PubMed |
description | Mutations in the spike glycoproteins of SARS-CoV-2 variants of concern have independently been shown to enhance aspects of spike protein fitness. Here, we describe an antibody fragment (V(H) ab6) that neutralizes all major variants including the recently emerged BA.1 and BA.2 Omicron subvariants, with a unique mode of binding revealed by cryo-EM studies. Further, we provide a comparative analysis of the mutational effects within previously emerged variant spikes and identify the structural role of mutations within the NTD and RBD in evading antibody neutralization. Our analysis shows that the highly mutated Gamma N-terminal domain exhibits considerable structural rearrangements, partially explaining its decreased neutralization by convalescent sera. Our results provide mechanistic insights into the structural, functional, and antigenic consequences of SARS-CoV-2 spike mutations and highlight a spike protein vulnerability that may be exploited to achieve broad protection against circulating variants. |
format | Online Article Text |
id | pubmed-9388680 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-93886802022-08-20 SARS-CoV-2 variants of concern: spike protein mutational analysis and epitope for broad neutralization Mannar, Dhiraj Saville, James W. Sun, Zehua Zhu, Xing Marti, Michelle M. Srivastava, Shanti S. Berezuk, Alison M. Zhou, Steven Tuttle, Katharine S. Sobolewski, Michele D. Kim, Andrew Treat, Benjamin R. Da Silva Castanha, Priscila Mayrelle Jacobs, Jana L. Barratt-Boyes, Simon M. Mellors, John W. Dimitrov, Dimiter S. Li, Wei Subramaniam, Sriram Nat Commun Article Mutations in the spike glycoproteins of SARS-CoV-2 variants of concern have independently been shown to enhance aspects of spike protein fitness. Here, we describe an antibody fragment (V(H) ab6) that neutralizes all major variants including the recently emerged BA.1 and BA.2 Omicron subvariants, with a unique mode of binding revealed by cryo-EM studies. Further, we provide a comparative analysis of the mutational effects within previously emerged variant spikes and identify the structural role of mutations within the NTD and RBD in evading antibody neutralization. Our analysis shows that the highly mutated Gamma N-terminal domain exhibits considerable structural rearrangements, partially explaining its decreased neutralization by convalescent sera. Our results provide mechanistic insights into the structural, functional, and antigenic consequences of SARS-CoV-2 spike mutations and highlight a spike protein vulnerability that may be exploited to achieve broad protection against circulating variants. Nature Publishing Group UK 2022-08-18 /pmc/articles/PMC9388680/ /pubmed/35982054 http://dx.doi.org/10.1038/s41467-022-32262-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Mannar, Dhiraj Saville, James W. Sun, Zehua Zhu, Xing Marti, Michelle M. Srivastava, Shanti S. Berezuk, Alison M. Zhou, Steven Tuttle, Katharine S. Sobolewski, Michele D. Kim, Andrew Treat, Benjamin R. Da Silva Castanha, Priscila Mayrelle Jacobs, Jana L. Barratt-Boyes, Simon M. Mellors, John W. Dimitrov, Dimiter S. Li, Wei Subramaniam, Sriram SARS-CoV-2 variants of concern: spike protein mutational analysis and epitope for broad neutralization |
title | SARS-CoV-2 variants of concern: spike protein mutational analysis and epitope for broad neutralization |
title_full | SARS-CoV-2 variants of concern: spike protein mutational analysis and epitope for broad neutralization |
title_fullStr | SARS-CoV-2 variants of concern: spike protein mutational analysis and epitope for broad neutralization |
title_full_unstemmed | SARS-CoV-2 variants of concern: spike protein mutational analysis and epitope for broad neutralization |
title_short | SARS-CoV-2 variants of concern: spike protein mutational analysis and epitope for broad neutralization |
title_sort | sars-cov-2 variants of concern: spike protein mutational analysis and epitope for broad neutralization |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9388680/ https://www.ncbi.nlm.nih.gov/pubmed/35982054 http://dx.doi.org/10.1038/s41467-022-32262-8 |
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