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Decoding the effects of spike receptor binding domain mutations on antibody escape abilities of omicron variants
Recent times witnessed an upsurge in the number of COVID19 cases which is primarily attributed to the emergence of several omicron variants, although there is substantial population vaccination coverage across the globe. Currently, many therapeutic antibodies have been approved for emergency usage....
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/PMC9395298/ https://www.ncbi.nlm.nih.gov/pubmed/36041326 http://dx.doi.org/10.1016/j.bbrc.2022.08.050 |
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author | Chakraborty, Sandipan Saha, Aditi Saha, Chiranjeet Ghosh, Sanjana Mondal, Trisha |
author_facet | Chakraborty, Sandipan Saha, Aditi Saha, Chiranjeet Ghosh, Sanjana Mondal, Trisha |
author_sort | Chakraborty, Sandipan |
collection | PubMed |
description | Recent times witnessed an upsurge in the number of COVID19 cases which is primarily attributed to the emergence of several omicron variants, although there is substantial population vaccination coverage across the globe. Currently, many therapeutic antibodies have been approved for emergency usage. The present study critically evaluates the effect of mutations observed in several omicron variants on the binding affinities of different classes of RBD-specific antibodies using a combined approach of immunoinformatics and binding free energy calculations. Our binding affinity data clearly show that omicron variants achieve antibody escape abilities by incorporating mutations at the immunogenic hotspot residues for each specific class of antibody. K417N and Y505H point mutations are primarily accountable for the loss of class I antibody binding affinities. The K417N/Q493R/Q498R/Y505H combined mutant significantly reduces binding affinities for all the class I antibodies. E484A single mutation, on the other hand, drastically reduces binding affinities for most of the class II antibodies. E484A and E484A/Q493R double mutations cause a 33–38% reduction in binding affinity for an approved therapeutic monoclonal antibody. The Q498R RBD mutation observed across all the omicron variants can reduce ∼12% binding affinity for REGN10987, a class III therapeutic antibody, and the L452R/Q498R double mutation causes a ∼6% decrease in binding affinities for another class III therapeutic antibody, LY-CoV1404. Our data suggest that achieving the immune evasion abilities appears to be the selection pressure behind the emergence of omicron variants. |
format | Online Article Text |
id | pubmed-9395298 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93952982022-08-23 Decoding the effects of spike receptor binding domain mutations on antibody escape abilities of omicron variants Chakraborty, Sandipan Saha, Aditi Saha, Chiranjeet Ghosh, Sanjana Mondal, Trisha Biochem Biophys Res Commun Article Recent times witnessed an upsurge in the number of COVID19 cases which is primarily attributed to the emergence of several omicron variants, although there is substantial population vaccination coverage across the globe. Currently, many therapeutic antibodies have been approved for emergency usage. The present study critically evaluates the effect of mutations observed in several omicron variants on the binding affinities of different classes of RBD-specific antibodies using a combined approach of immunoinformatics and binding free energy calculations. Our binding affinity data clearly show that omicron variants achieve antibody escape abilities by incorporating mutations at the immunogenic hotspot residues for each specific class of antibody. K417N and Y505H point mutations are primarily accountable for the loss of class I antibody binding affinities. The K417N/Q493R/Q498R/Y505H combined mutant significantly reduces binding affinities for all the class I antibodies. E484A single mutation, on the other hand, drastically reduces binding affinities for most of the class II antibodies. E484A and E484A/Q493R double mutations cause a 33–38% reduction in binding affinity for an approved therapeutic monoclonal antibody. The Q498R RBD mutation observed across all the omicron variants can reduce ∼12% binding affinity for REGN10987, a class III therapeutic antibody, and the L452R/Q498R double mutation causes a ∼6% decrease in binding affinities for another class III therapeutic antibody, LY-CoV1404. Our data suggest that achieving the immune evasion abilities appears to be the selection pressure behind the emergence of omicron variants. Elsevier Inc. 2022-10-30 2022-08-23 /pmc/articles/PMC9395298/ /pubmed/36041326 http://dx.doi.org/10.1016/j.bbrc.2022.08.050 Text en © 2022 Elsevier Inc. All rights reserved. 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 | Article Chakraborty, Sandipan Saha, Aditi Saha, Chiranjeet Ghosh, Sanjana Mondal, Trisha Decoding the effects of spike receptor binding domain mutations on antibody escape abilities of omicron variants |
title | Decoding the effects of spike receptor binding domain mutations on antibody escape abilities of omicron variants |
title_full | Decoding the effects of spike receptor binding domain mutations on antibody escape abilities of omicron variants |
title_fullStr | Decoding the effects of spike receptor binding domain mutations on antibody escape abilities of omicron variants |
title_full_unstemmed | Decoding the effects of spike receptor binding domain mutations on antibody escape abilities of omicron variants |
title_short | Decoding the effects of spike receptor binding domain mutations on antibody escape abilities of omicron variants |
title_sort | decoding the effects of spike receptor binding domain mutations on antibody escape abilities of omicron variants |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9395298/ https://www.ncbi.nlm.nih.gov/pubmed/36041326 http://dx.doi.org/10.1016/j.bbrc.2022.08.050 |
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