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SARS-CoV-2 Variants of Concern and Variants of Interest Receptor Binding Domain Mutations and Virus Infectivity

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has lasted more than 2 years with over 260 million infections and 5 million deaths worldwide as of November 2021. To combat the virus, monoclonal antibodies blocking the virus binding to human receptor, the angiotensin convert...

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Autores principales: Liu, Haolin, Wei, Pengcheng, Kappler, John W., Marrack, Philippa, Zhang, Gongyi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8828474/
https://www.ncbi.nlm.nih.gov/pubmed/35154144
http://dx.doi.org/10.3389/fimmu.2022.825256
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author Liu, Haolin
Wei, Pengcheng
Kappler, John W.
Marrack, Philippa
Zhang, Gongyi
author_facet Liu, Haolin
Wei, Pengcheng
Kappler, John W.
Marrack, Philippa
Zhang, Gongyi
author_sort Liu, Haolin
collection PubMed
description The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has lasted more than 2 years with over 260 million infections and 5 million deaths worldwide as of November 2021. To combat the virus, monoclonal antibodies blocking the virus binding to human receptor, the angiotensin converting enzyme 2 (ACE2), have been approved to treat the infected patients. Inactivated whole virus or the full-length virus spike encoding adenovirus or mRNA vaccines are being used to immunize the public. However, SARS-CoV-2 variants are emerging. These, to some extent, escape neutralization by the therapeutic antibodies and vaccine-induced immunity. Thus, breakthrough infections by SARS-CoV-2 variants have been reported in previously virus-infected or fully vaccinated individuals. The receptor binding domain (RBD) of the virus spike protein reacts with host ACE2, leading to the entry of the virus into the cell. It is also the major antigenic site of the virus, with more than 90% of broadly neutralizing antibodies from either infected patients or vaccinated individuals targeting the spike RBD. Therefore, mutations in the RBD region are effective ways for SARS-CoV-2 variants to gain infectivity and escape the immunity built up by the original vaccines or infections. In this review, we focus on the impact of RBD mutations in SARS-CoV-2 variants of concern (VOC) and variants of interest (VOI) on ACE2 binding affinity and escape of serum antibody neutralization. We also provide protein structure models to show how the VOC and VOI RBD mutations affect ACE2 binding and allow escape of the virus from the therapeutic antibody, bamlanivimab.
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spelling pubmed-88284742022-02-11 SARS-CoV-2 Variants of Concern and Variants of Interest Receptor Binding Domain Mutations and Virus Infectivity Liu, Haolin Wei, Pengcheng Kappler, John W. Marrack, Philippa Zhang, Gongyi Front Immunol Immunology The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has lasted more than 2 years with over 260 million infections and 5 million deaths worldwide as of November 2021. To combat the virus, monoclonal antibodies blocking the virus binding to human receptor, the angiotensin converting enzyme 2 (ACE2), have been approved to treat the infected patients. Inactivated whole virus or the full-length virus spike encoding adenovirus or mRNA vaccines are being used to immunize the public. However, SARS-CoV-2 variants are emerging. These, to some extent, escape neutralization by the therapeutic antibodies and vaccine-induced immunity. Thus, breakthrough infections by SARS-CoV-2 variants have been reported in previously virus-infected or fully vaccinated individuals. The receptor binding domain (RBD) of the virus spike protein reacts with host ACE2, leading to the entry of the virus into the cell. It is also the major antigenic site of the virus, with more than 90% of broadly neutralizing antibodies from either infected patients or vaccinated individuals targeting the spike RBD. Therefore, mutations in the RBD region are effective ways for SARS-CoV-2 variants to gain infectivity and escape the immunity built up by the original vaccines or infections. In this review, we focus on the impact of RBD mutations in SARS-CoV-2 variants of concern (VOC) and variants of interest (VOI) on ACE2 binding affinity and escape of serum antibody neutralization. We also provide protein structure models to show how the VOC and VOI RBD mutations affect ACE2 binding and allow escape of the virus from the therapeutic antibody, bamlanivimab. Frontiers Media S.A. 2022-01-27 /pmc/articles/PMC8828474/ /pubmed/35154144 http://dx.doi.org/10.3389/fimmu.2022.825256 Text en Copyright © 2022 Liu, Wei, Kappler, Marrack and Zhang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Liu, Haolin
Wei, Pengcheng
Kappler, John W.
Marrack, Philippa
Zhang, Gongyi
SARS-CoV-2 Variants of Concern and Variants of Interest Receptor Binding Domain Mutations and Virus Infectivity
title SARS-CoV-2 Variants of Concern and Variants of Interest Receptor Binding Domain Mutations and Virus Infectivity
title_full SARS-CoV-2 Variants of Concern and Variants of Interest Receptor Binding Domain Mutations and Virus Infectivity
title_fullStr SARS-CoV-2 Variants of Concern and Variants of Interest Receptor Binding Domain Mutations and Virus Infectivity
title_full_unstemmed SARS-CoV-2 Variants of Concern and Variants of Interest Receptor Binding Domain Mutations and Virus Infectivity
title_short SARS-CoV-2 Variants of Concern and Variants of Interest Receptor Binding Domain Mutations and Virus Infectivity
title_sort sars-cov-2 variants of concern and variants of interest receptor binding domain mutations and virus infectivity
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8828474/
https://www.ncbi.nlm.nih.gov/pubmed/35154144
http://dx.doi.org/10.3389/fimmu.2022.825256
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