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Exploring antibody repurposing for COVID-19: beyond presumed roles of therapeutic antibodies
The urgent need for a treatment of COVID-19 has left researchers with limited choice of either developing an effective vaccine or identifying approved/investigational drugs developed for other medical conditions for potential repurposing, thus bypassing long clinical trials. In this work, we compare...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119408/ https://www.ncbi.nlm.nih.gov/pubmed/33986382 http://dx.doi.org/10.1038/s41598-021-89621-6 |
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author | Rawat, Puneet Sharma, Divya Srivastava, Ambuj Janakiraman, Vani Gromiha, M. Michael |
author_facet | Rawat, Puneet Sharma, Divya Srivastava, Ambuj Janakiraman, Vani Gromiha, M. Michael |
author_sort | Rawat, Puneet |
collection | PubMed |
description | The urgent need for a treatment of COVID-19 has left researchers with limited choice of either developing an effective vaccine or identifying approved/investigational drugs developed for other medical conditions for potential repurposing, thus bypassing long clinical trials. In this work, we compared the sequences of experimentally verified SARS-CoV-2 neutralizing antibodies and sequentially/structurally similar commercialized therapeutic monoclonal antibodies. We have identified three therapeutic antibodies, Tremelimumab, Ipilimumab and Afasevikumab. Interestingly, these antibodies target CTLA4 and IL17A, levels of which have been shown to be elevated during severe SARS-CoV-2 infection. The candidate antibodies were evaluated further for epitope restriction, interaction energy and interaction surface to gauge their repurposability to tackle SARS-CoV-2 infection. Our work provides candidate antibody scaffolds with dual activities of plausible viral neutralization and immunosuppression. Further, these candidate antibodies can also be explored in diagnostic test kits for SARS-CoV-2 infection. We opine that this in silico workflow to screen and analyze antibodies for repurposing would have widespread applications. |
format | Online Article Text |
id | pubmed-8119408 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-81194082021-05-14 Exploring antibody repurposing for COVID-19: beyond presumed roles of therapeutic antibodies Rawat, Puneet Sharma, Divya Srivastava, Ambuj Janakiraman, Vani Gromiha, M. Michael Sci Rep Article The urgent need for a treatment of COVID-19 has left researchers with limited choice of either developing an effective vaccine or identifying approved/investigational drugs developed for other medical conditions for potential repurposing, thus bypassing long clinical trials. In this work, we compared the sequences of experimentally verified SARS-CoV-2 neutralizing antibodies and sequentially/structurally similar commercialized therapeutic monoclonal antibodies. We have identified three therapeutic antibodies, Tremelimumab, Ipilimumab and Afasevikumab. Interestingly, these antibodies target CTLA4 and IL17A, levels of which have been shown to be elevated during severe SARS-CoV-2 infection. The candidate antibodies were evaluated further for epitope restriction, interaction energy and interaction surface to gauge their repurposability to tackle SARS-CoV-2 infection. Our work provides candidate antibody scaffolds with dual activities of plausible viral neutralization and immunosuppression. Further, these candidate antibodies can also be explored in diagnostic test kits for SARS-CoV-2 infection. We opine that this in silico workflow to screen and analyze antibodies for repurposing would have widespread applications. Nature Publishing Group UK 2021-05-13 /pmc/articles/PMC8119408/ /pubmed/33986382 http://dx.doi.org/10.1038/s41598-021-89621-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Rawat, Puneet Sharma, Divya Srivastava, Ambuj Janakiraman, Vani Gromiha, M. Michael Exploring antibody repurposing for COVID-19: beyond presumed roles of therapeutic antibodies |
title | Exploring antibody repurposing for COVID-19: beyond presumed roles of therapeutic antibodies |
title_full | Exploring antibody repurposing for COVID-19: beyond presumed roles of therapeutic antibodies |
title_fullStr | Exploring antibody repurposing for COVID-19: beyond presumed roles of therapeutic antibodies |
title_full_unstemmed | Exploring antibody repurposing for COVID-19: beyond presumed roles of therapeutic antibodies |
title_short | Exploring antibody repurposing for COVID-19: beyond presumed roles of therapeutic antibodies |
title_sort | exploring antibody repurposing for covid-19: beyond presumed roles of therapeutic antibodies |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119408/ https://www.ncbi.nlm.nih.gov/pubmed/33986382 http://dx.doi.org/10.1038/s41598-021-89621-6 |
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