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SARS-CoV-2 Omicron variant: Antibody evasion and cryo-EM structure of spike protein–ACE2 complex
The newly reported Omicron variant is poised to replace Delta as the most prevalent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant across the world. Cryo–electron microscopy (cryo-EM) structural analysis of the Omicron variant spike protein in complex with human angiotensin-con...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9799367/ https://www.ncbi.nlm.nih.gov/pubmed/35050643 http://dx.doi.org/10.1126/science.abn7760 |
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author | Mannar, Dhiraj Saville, James W. Zhu, Xing Srivastava, Shanti S. Berezuk, Alison M. Tuttle, Katharine S. Marquez, Ana Citlali Sekirov, Inna Subramaniam, Sriram |
author_facet | Mannar, Dhiraj Saville, James W. Zhu, Xing Srivastava, Shanti S. Berezuk, Alison M. Tuttle, Katharine S. Marquez, Ana Citlali Sekirov, Inna Subramaniam, Sriram |
author_sort | Mannar, Dhiraj |
collection | PubMed |
description | The newly reported Omicron variant is poised to replace Delta as the most prevalent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant across the world. Cryo–electron microscopy (cryo-EM) structural analysis of the Omicron variant spike protein in complex with human angiotensin-converting enzyme 2 (ACE2) reveals new salt bridges and hydrogen bonds formed by mutated residues arginine-493, serine-496, and arginine-498 in the receptor binding domain with ACE2. These interactions appear to compensate for other Omicron mutations such as the substitution of asparagine for lysine at position 417 (K417N) that are known to reduce ACE2 binding affinity, resulting in similar biochemical ACE2 binding affinities for the Delta and Omicron variants. Neutralization assays show that pseudoviruses that display the Omicron spike protein exhibit increased antibody evasion. The increase in antibody evasion and the retention of strong interactions at the ACE2 interface thus represent important molecular features that likely contribute to the rapid spread of the Omicron variant. |
format | Online Article Text |
id | pubmed-9799367 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-97993672023-01-06 SARS-CoV-2 Omicron variant: Antibody evasion and cryo-EM structure of spike protein–ACE2 complex Mannar, Dhiraj Saville, James W. Zhu, Xing Srivastava, Shanti S. Berezuk, Alison M. Tuttle, Katharine S. Marquez, Ana Citlali Sekirov, Inna Subramaniam, Sriram Science Reports The newly reported Omicron variant is poised to replace Delta as the most prevalent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant across the world. Cryo–electron microscopy (cryo-EM) structural analysis of the Omicron variant spike protein in complex with human angiotensin-converting enzyme 2 (ACE2) reveals new salt bridges and hydrogen bonds formed by mutated residues arginine-493, serine-496, and arginine-498 in the receptor binding domain with ACE2. These interactions appear to compensate for other Omicron mutations such as the substitution of asparagine for lysine at position 417 (K417N) that are known to reduce ACE2 binding affinity, resulting in similar biochemical ACE2 binding affinities for the Delta and Omicron variants. Neutralization assays show that pseudoviruses that display the Omicron spike protein exhibit increased antibody evasion. The increase in antibody evasion and the retention of strong interactions at the ACE2 interface thus represent important molecular features that likely contribute to the rapid spread of the Omicron variant. American Association for the Advancement of Science 2022-01-20 2022-02-18 /pmc/articles/PMC9799367/ /pubmed/35050643 http://dx.doi.org/10.1126/science.abn7760 Text en Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). 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 work is properly cited. |
spellingShingle | Reports Mannar, Dhiraj Saville, James W. Zhu, Xing Srivastava, Shanti S. Berezuk, Alison M. Tuttle, Katharine S. Marquez, Ana Citlali Sekirov, Inna Subramaniam, Sriram SARS-CoV-2 Omicron variant: Antibody evasion and cryo-EM structure of spike protein–ACE2 complex |
title | SARS-CoV-2 Omicron variant: Antibody evasion and cryo-EM structure of spike protein–ACE2 complex |
title_full | SARS-CoV-2 Omicron variant: Antibody evasion and cryo-EM structure of spike protein–ACE2 complex |
title_fullStr | SARS-CoV-2 Omicron variant: Antibody evasion and cryo-EM structure of spike protein–ACE2 complex |
title_full_unstemmed | SARS-CoV-2 Omicron variant: Antibody evasion and cryo-EM structure of spike protein–ACE2 complex |
title_short | SARS-CoV-2 Omicron variant: Antibody evasion and cryo-EM structure of spike protein–ACE2 complex |
title_sort | sars-cov-2 omicron variant: antibody evasion and cryo-em structure of spike protein–ace2 complex |
topic | Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9799367/ https://www.ncbi.nlm.nih.gov/pubmed/35050643 http://dx.doi.org/10.1126/science.abn7760 |
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