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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
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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. |
format | Online Article Text |
id | pubmed-9897577 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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