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SARS-CoV-2 receptor-binding mutations and antibody contact sites

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations can impact infectivity, viral load, and overall morbidity/mortality during infection. In this analysis, we look at the mutational landscape of the SARS-CoV-2 receptor-binding domain, a structure that is antigenic and allows for v...

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Autores principales: Mejdani, Marios, Haddadi, Kiandokht, Pham, Chester, Mahadevan, Radhakrishnan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353666/
https://www.ncbi.nlm.nih.gov/pubmed/34386694
http://dx.doi.org/10.1093/abt/tbab015
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author Mejdani, Marios
Haddadi, Kiandokht
Pham, Chester
Mahadevan, Radhakrishnan
author_facet Mejdani, Marios
Haddadi, Kiandokht
Pham, Chester
Mahadevan, Radhakrishnan
author_sort Mejdani, Marios
collection PubMed
description Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations can impact infectivity, viral load, and overall morbidity/mortality during infection. In this analysis, we look at the mutational landscape of the SARS-CoV-2 receptor-binding domain, a structure that is antigenic and allows for viral binding to the host. We develop a bioinformatics platform and analyze 104 193 Global Initiative on Sharing All Influenza Data sequences acquired on 15 October 2020, with a majority of sequences (96%) containing point mutations. We report high frequency mutations with improved binding affinity to ACE2 including S477N, N439K, V367F, and N501Y and address the potential impact of RBD mutations on antibody binding. The high frequency S477N mutation is present in 6.7% of all SARS-CoV-2 sequences, co-occurs with D614G, and is currently present in 14 countries. To address RBD-antibody interactions, we take a subset of human-derived antibodies and define their interacting residues using PDBsum. Our analysis shows that RBD mutations were found in approximately 9% of our dataset, with some mutations improving RBD-ACE2 interactions. We also show that antibody-mediated immunity against SARS-CoV-2 enlists broad coverage of the RBD, with multiple antibodies targeting a variety of RBD regions. These data suggest that it is unlikely for neutralization/RBD antibody binding to be significantly impacted, as a whole, in the presence of RBD point mutations that conserve the RBD structure.
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spelling pubmed-83536662021-08-11 SARS-CoV-2 receptor-binding mutations and antibody contact sites Mejdani, Marios Haddadi, Kiandokht Pham, Chester Mahadevan, Radhakrishnan Antib Ther Original Research Article Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations can impact infectivity, viral load, and overall morbidity/mortality during infection. In this analysis, we look at the mutational landscape of the SARS-CoV-2 receptor-binding domain, a structure that is antigenic and allows for viral binding to the host. We develop a bioinformatics platform and analyze 104 193 Global Initiative on Sharing All Influenza Data sequences acquired on 15 October 2020, with a majority of sequences (96%) containing point mutations. We report high frequency mutations with improved binding affinity to ACE2 including S477N, N439K, V367F, and N501Y and address the potential impact of RBD mutations on antibody binding. The high frequency S477N mutation is present in 6.7% of all SARS-CoV-2 sequences, co-occurs with D614G, and is currently present in 14 countries. To address RBD-antibody interactions, we take a subset of human-derived antibodies and define their interacting residues using PDBsum. Our analysis shows that RBD mutations were found in approximately 9% of our dataset, with some mutations improving RBD-ACE2 interactions. We also show that antibody-mediated immunity against SARS-CoV-2 enlists broad coverage of the RBD, with multiple antibodies targeting a variety of RBD regions. These data suggest that it is unlikely for neutralization/RBD antibody binding to be significantly impacted, as a whole, in the presence of RBD point mutations that conserve the RBD structure. Oxford University Press 2021-07-22 /pmc/articles/PMC8353666/ /pubmed/34386694 http://dx.doi.org/10.1093/abt/tbab015 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of Antibody Therapeutics. All rights reserved. For Permissions, please email: journals.permissions@oup.com https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Research Article
Mejdani, Marios
Haddadi, Kiandokht
Pham, Chester
Mahadevan, Radhakrishnan
SARS-CoV-2 receptor-binding mutations and antibody contact sites
title SARS-CoV-2 receptor-binding mutations and antibody contact sites
title_full SARS-CoV-2 receptor-binding mutations and antibody contact sites
title_fullStr SARS-CoV-2 receptor-binding mutations and antibody contact sites
title_full_unstemmed SARS-CoV-2 receptor-binding mutations and antibody contact sites
title_short SARS-CoV-2 receptor-binding mutations and antibody contact sites
title_sort sars-cov-2 receptor-binding mutations and antibody contact sites
topic Original Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353666/
https://www.ncbi.nlm.nih.gov/pubmed/34386694
http://dx.doi.org/10.1093/abt/tbab015
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