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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...

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Autores principales: Rawat, Puneet, Sharma, Divya, Srivastava, Ambuj, Janakiraman, Vani, Gromiha, M. Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
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.
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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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