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Mitoxantrone dihydrochloride, an FDA approved drug, binds with SARS-CoV-2 NSP1 C-terminal

One of the major virulence factors of SARS-CoV-2, NSP1, is a vital drug target due to its role in host immune evasion through multiple pathways. NSP1 protein is associated with inhibiting host mRNA translation by binding to the small subunit of ribosome through its C-terminal region. Previously, we...

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Detalles Bibliográficos
Autores principales: Kumar, Prateek, Bhardwaj, Taniya, Giri, Rajanish
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8981793/
https://www.ncbi.nlm.nih.gov/pubmed/35425590
http://dx.doi.org/10.1039/d1ra07434b
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author Kumar, Prateek
Bhardwaj, Taniya
Giri, Rajanish
author_facet Kumar, Prateek
Bhardwaj, Taniya
Giri, Rajanish
author_sort Kumar, Prateek
collection PubMed
description One of the major virulence factors of SARS-CoV-2, NSP1, is a vital drug target due to its role in host immune evasion through multiple pathways. NSP1 protein is associated with inhibiting host mRNA translation by binding to the small subunit of ribosome through its C-terminal region. Previously, we have shown the structural dynamics of the NSP1 C-terminal region (NSP1-CTR) in different physiological environments. So, it would be very interesting to investigate the druggable compounds that could bind with NSP1-CTR. Here, in this article, we have performed different spectroscopic technique-based binding assays of an anticancer drug mitoxantrone dihydrochloride (MTX) against the NSP1-CTR. We have also performed molecular dynamics simulations of the docked complex with two different force fields up to one microsecond. Overall, our results have suggested good binding between NSP1-CTR and MTX and may have implications in developing therapeutic strategies targeting the NSP1 protein of SARS-CoV-2.
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spelling pubmed-89817932022-04-13 Mitoxantrone dihydrochloride, an FDA approved drug, binds with SARS-CoV-2 NSP1 C-terminal Kumar, Prateek Bhardwaj, Taniya Giri, Rajanish RSC Adv Chemistry One of the major virulence factors of SARS-CoV-2, NSP1, is a vital drug target due to its role in host immune evasion through multiple pathways. NSP1 protein is associated with inhibiting host mRNA translation by binding to the small subunit of ribosome through its C-terminal region. Previously, we have shown the structural dynamics of the NSP1 C-terminal region (NSP1-CTR) in different physiological environments. So, it would be very interesting to investigate the druggable compounds that could bind with NSP1-CTR. Here, in this article, we have performed different spectroscopic technique-based binding assays of an anticancer drug mitoxantrone dihydrochloride (MTX) against the NSP1-CTR. We have also performed molecular dynamics simulations of the docked complex with two different force fields up to one microsecond. Overall, our results have suggested good binding between NSP1-CTR and MTX and may have implications in developing therapeutic strategies targeting the NSP1 protein of SARS-CoV-2. The Royal Society of Chemistry 2022-02-16 /pmc/articles/PMC8981793/ /pubmed/35425590 http://dx.doi.org/10.1039/d1ra07434b Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Kumar, Prateek
Bhardwaj, Taniya
Giri, Rajanish
Mitoxantrone dihydrochloride, an FDA approved drug, binds with SARS-CoV-2 NSP1 C-terminal
title Mitoxantrone dihydrochloride, an FDA approved drug, binds with SARS-CoV-2 NSP1 C-terminal
title_full Mitoxantrone dihydrochloride, an FDA approved drug, binds with SARS-CoV-2 NSP1 C-terminal
title_fullStr Mitoxantrone dihydrochloride, an FDA approved drug, binds with SARS-CoV-2 NSP1 C-terminal
title_full_unstemmed Mitoxantrone dihydrochloride, an FDA approved drug, binds with SARS-CoV-2 NSP1 C-terminal
title_short Mitoxantrone dihydrochloride, an FDA approved drug, binds with SARS-CoV-2 NSP1 C-terminal
title_sort mitoxantrone dihydrochloride, an fda approved drug, binds with sars-cov-2 nsp1 c-terminal
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8981793/
https://www.ncbi.nlm.nih.gov/pubmed/35425590
http://dx.doi.org/10.1039/d1ra07434b
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