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Antibody accessibility determines location of spike surface mutations in SARS-CoV-2 variants

The steady emergence of SARS-CoV-2 variants gives us a real-time view of the interplay between viral evolution and the host immune defense. The spike protein of SARS-CoV-2 is the primary target of antibodies. Here, we show that steric accessibility to antibodies provides a strong predictor of mutati...

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Autores principales: von Bülow, Sören, Sikora, Mateusz, Blanc, Florian E. C., Covino, Roberto, Hummer, Gerhard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9897577/
https://www.ncbi.nlm.nih.gov/pubmed/36693110
http://dx.doi.org/10.1371/journal.pcbi.1010822
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author von Bülow, Sören
Sikora, Mateusz
Blanc, Florian E. C.
Covino, Roberto
Hummer, Gerhard
author_facet von Bülow, Sören
Sikora, Mateusz
Blanc, Florian E. C.
Covino, Roberto
Hummer, Gerhard
author_sort von Bülow, Sören
collection PubMed
description The steady emergence of SARS-CoV-2 variants gives us a real-time view of the interplay between viral evolution and the host immune defense. The spike protein of SARS-CoV-2 is the primary target of antibodies. Here, we show that steric accessibility to antibodies provides a strong predictor of mutation activity in the spike protein of SARS-CoV-2 variants, including Omicron. We introduce an antibody accessibility score (AAS) that accounts for the steric shielding effect of glycans at the surface of spike. We find that high values of the AAS correlate strongly with the sites of mutations in the spike proteins of newly emerging SARS-CoV-2 variants. We use the AAS to assess the escapability of variant spike proteins, i.e., their ability to escape antibody-based immune responses. The high calculated escapability of the Omicron variant BA.5 with respect to both wild-type (WT) vaccination and BA.1 infection is consistent with its rapid spread despite high rates of vaccination and prior infection with earlier variants. We calculated the AAS from structural and molecular dynamics simulation data that were available early in the pandemic, in the spring of 2020. The AAS thus allows us to prospectively assess the ability of variant spike proteins to escape antibody-based immune responses and to pinpoint regions of expected mutation activity in future variants.
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spelling pubmed-98975772023-02-04 Antibody accessibility determines location of spike surface mutations in SARS-CoV-2 variants von Bülow, Sören Sikora, Mateusz Blanc, Florian E. C. Covino, Roberto Hummer, Gerhard PLoS Comput Biol Research Article The steady emergence of SARS-CoV-2 variants gives us a real-time view of the interplay between viral evolution and the host immune defense. The spike protein of SARS-CoV-2 is the primary target of antibodies. Here, we show that steric accessibility to antibodies provides a strong predictor of mutation activity in the spike protein of SARS-CoV-2 variants, including Omicron. We introduce an antibody accessibility score (AAS) that accounts for the steric shielding effect of glycans at the surface of spike. We find that high values of the AAS correlate strongly with the sites of mutations in the spike proteins of newly emerging SARS-CoV-2 variants. We use the AAS to assess the escapability of variant spike proteins, i.e., their ability to escape antibody-based immune responses. The high calculated escapability of the Omicron variant BA.5 with respect to both wild-type (WT) vaccination and BA.1 infection is consistent with its rapid spread despite high rates of vaccination and prior infection with earlier variants. We calculated the AAS from structural and molecular dynamics simulation data that were available early in the pandemic, in the spring of 2020. The AAS thus allows us to prospectively assess the ability of variant spike proteins to escape antibody-based immune responses and to pinpoint regions of expected mutation activity in future variants. Public Library of Science 2023-01-24 /pmc/articles/PMC9897577/ /pubmed/36693110 http://dx.doi.org/10.1371/journal.pcbi.1010822 Text en © 2023 von Bülow et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
von Bülow, Sören
Sikora, Mateusz
Blanc, Florian E. C.
Covino, Roberto
Hummer, Gerhard
Antibody accessibility determines location of spike surface mutations in SARS-CoV-2 variants
title Antibody accessibility determines location of spike surface mutations in SARS-CoV-2 variants
title_full Antibody accessibility determines location of spike surface mutations in SARS-CoV-2 variants
title_fullStr Antibody accessibility determines location of spike surface mutations in SARS-CoV-2 variants
title_full_unstemmed Antibody accessibility determines location of spike surface mutations in SARS-CoV-2 variants
title_short Antibody accessibility determines location of spike surface mutations in SARS-CoV-2 variants
title_sort antibody accessibility determines location of spike surface mutations in sars-cov-2 variants
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9897577/
https://www.ncbi.nlm.nih.gov/pubmed/36693110
http://dx.doi.org/10.1371/journal.pcbi.1010822
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