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Antibody escape and cryptic cross-domain stabilization in the SARS-CoV-2 Omicron spike protein
The worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the repeated emergence of variants of concern. For the Omicron variant, sub-lineages BA.1 and BA.2, respectively, contain 33 and 29 nonsynonymous and indel spike protein mutations. These amino acid substi...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9350683/ https://www.ncbi.nlm.nih.gov/pubmed/35988543 http://dx.doi.org/10.1016/j.chom.2022.07.016 |
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author | Javanmardi, Kamyab Segall-Shapiro, Thomas H. Chou, Chia-Wei Boutz, Daniel R. Olsen, Randall J. Xie, Xuping Xia, Hongjie Shi, Pei-Yong Johnson, Charlie D. Annapareddy, Ankur Weaver, Scott Musser, James M. Ellington, Andrew D. Finkelstein, Ilya J. Gollihar, Jimmy D. |
author_facet | Javanmardi, Kamyab Segall-Shapiro, Thomas H. Chou, Chia-Wei Boutz, Daniel R. Olsen, Randall J. Xie, Xuping Xia, Hongjie Shi, Pei-Yong Johnson, Charlie D. Annapareddy, Ankur Weaver, Scott Musser, James M. Ellington, Andrew D. Finkelstein, Ilya J. Gollihar, Jimmy D. |
author_sort | Javanmardi, Kamyab |
collection | PubMed |
description | The worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the repeated emergence of variants of concern. For the Omicron variant, sub-lineages BA.1 and BA.2, respectively, contain 33 and 29 nonsynonymous and indel spike protein mutations. These amino acid substitutions and indels are implicated in increased transmissibility and enhanced immune evasion. By reverting individual spike mutations of BA.1 or BA.2, we characterize the molecular effects of the Omicron spike mutations on expression, ACE2 receptor affinity, and neutralizing antibody recognition. We identified key mutations enabling escape from neutralizing antibodies at a variety of epitopes. Stabilizing mutations in the N-terminal and S2 domains of the spike protein can compensate for destabilizing mutations in the receptor binding domain, enabling the record number of mutations in Omicron. Our results provide a comprehensive account of the mutational effects in the Omicron spike protein and illustrate previously uncharacterized mechanisms of host evasion. |
format | Online Article Text |
id | pubmed-9350683 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93506832022-08-04 Antibody escape and cryptic cross-domain stabilization in the SARS-CoV-2 Omicron spike protein Javanmardi, Kamyab Segall-Shapiro, Thomas H. Chou, Chia-Wei Boutz, Daniel R. Olsen, Randall J. Xie, Xuping Xia, Hongjie Shi, Pei-Yong Johnson, Charlie D. Annapareddy, Ankur Weaver, Scott Musser, James M. Ellington, Andrew D. Finkelstein, Ilya J. Gollihar, Jimmy D. Cell Host Microbe Short Article The worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the repeated emergence of variants of concern. For the Omicron variant, sub-lineages BA.1 and BA.2, respectively, contain 33 and 29 nonsynonymous and indel spike protein mutations. These amino acid substitutions and indels are implicated in increased transmissibility and enhanced immune evasion. By reverting individual spike mutations of BA.1 or BA.2, we characterize the molecular effects of the Omicron spike mutations on expression, ACE2 receptor affinity, and neutralizing antibody recognition. We identified key mutations enabling escape from neutralizing antibodies at a variety of epitopes. Stabilizing mutations in the N-terminal and S2 domains of the spike protein can compensate for destabilizing mutations in the receptor binding domain, enabling the record number of mutations in Omicron. Our results provide a comprehensive account of the mutational effects in the Omicron spike protein and illustrate previously uncharacterized mechanisms of host evasion. Elsevier Inc. 2022-09-14 2022-08-04 /pmc/articles/PMC9350683/ /pubmed/35988543 http://dx.doi.org/10.1016/j.chom.2022.07.016 Text en © 2022 Elsevier Inc. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Short Article Javanmardi, Kamyab Segall-Shapiro, Thomas H. Chou, Chia-Wei Boutz, Daniel R. Olsen, Randall J. Xie, Xuping Xia, Hongjie Shi, Pei-Yong Johnson, Charlie D. Annapareddy, Ankur Weaver, Scott Musser, James M. Ellington, Andrew D. Finkelstein, Ilya J. Gollihar, Jimmy D. Antibody escape and cryptic cross-domain stabilization in the SARS-CoV-2 Omicron spike protein |
title | Antibody escape and cryptic cross-domain stabilization in the SARS-CoV-2 Omicron spike protein |
title_full | Antibody escape and cryptic cross-domain stabilization in the SARS-CoV-2 Omicron spike protein |
title_fullStr | Antibody escape and cryptic cross-domain stabilization in the SARS-CoV-2 Omicron spike protein |
title_full_unstemmed | Antibody escape and cryptic cross-domain stabilization in the SARS-CoV-2 Omicron spike protein |
title_short | Antibody escape and cryptic cross-domain stabilization in the SARS-CoV-2 Omicron spike protein |
title_sort | antibody escape and cryptic cross-domain stabilization in the sars-cov-2 omicron spike protein |
topic | Short Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9350683/ https://www.ncbi.nlm.nih.gov/pubmed/35988543 http://dx.doi.org/10.1016/j.chom.2022.07.016 |
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