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Zika M—A Potential Viroporin: Mutational Study and Drug Repurposing

Genus Flavivirus contains several important human pathogens. Among these, the Zika virus is an emerging etiological agent that merits concern. One of its structural proteins, prM, plays an essential role in viral maturation and assembly, making it an attractive drug and vaccine development target. H...

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Autores principales: Tomar, Prabhat Pratap Singh, Krugliak, Miriam, Singh, Anamika, Arkin, Isaiah T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8944957/
https://www.ncbi.nlm.nih.gov/pubmed/35327443
http://dx.doi.org/10.3390/biomedicines10030641
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author Tomar, Prabhat Pratap Singh
Krugliak, Miriam
Singh, Anamika
Arkin, Isaiah T.
author_facet Tomar, Prabhat Pratap Singh
Krugliak, Miriam
Singh, Anamika
Arkin, Isaiah T.
author_sort Tomar, Prabhat Pratap Singh
collection PubMed
description Genus Flavivirus contains several important human pathogens. Among these, the Zika virus is an emerging etiological agent that merits concern. One of its structural proteins, prM, plays an essential role in viral maturation and assembly, making it an attractive drug and vaccine development target. Herein, we have characterized ZikV-M as a potential viroporin candidate using three different bacteria-based assays. These assays were subsequently employed to screen a library of repurposed drugs from which ten compounds were identified as ZikV-M blockers. Mutational analyses of conserved amino acids in the transmembrane domain of other flaviviruses, including West Nile and Dengue virus, were performed to study their role in ion channel activity. In conclusion, our data show that ZikV-M is a potential ion channel that can be used as a drug target for high throughput screening and drug repurposing.
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spelling pubmed-89449572022-03-25 Zika M—A Potential Viroporin: Mutational Study and Drug Repurposing Tomar, Prabhat Pratap Singh Krugliak, Miriam Singh, Anamika Arkin, Isaiah T. Biomedicines Article Genus Flavivirus contains several important human pathogens. Among these, the Zika virus is an emerging etiological agent that merits concern. One of its structural proteins, prM, plays an essential role in viral maturation and assembly, making it an attractive drug and vaccine development target. Herein, we have characterized ZikV-M as a potential viroporin candidate using three different bacteria-based assays. These assays were subsequently employed to screen a library of repurposed drugs from which ten compounds were identified as ZikV-M blockers. Mutational analyses of conserved amino acids in the transmembrane domain of other flaviviruses, including West Nile and Dengue virus, were performed to study their role in ion channel activity. In conclusion, our data show that ZikV-M is a potential ion channel that can be used as a drug target for high throughput screening and drug repurposing. MDPI 2022-03-10 /pmc/articles/PMC8944957/ /pubmed/35327443 http://dx.doi.org/10.3390/biomedicines10030641 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tomar, Prabhat Pratap Singh
Krugliak, Miriam
Singh, Anamika
Arkin, Isaiah T.
Zika M—A Potential Viroporin: Mutational Study and Drug Repurposing
title Zika M—A Potential Viroporin: Mutational Study and Drug Repurposing
title_full Zika M—A Potential Viroporin: Mutational Study and Drug Repurposing
title_fullStr Zika M—A Potential Viroporin: Mutational Study and Drug Repurposing
title_full_unstemmed Zika M—A Potential Viroporin: Mutational Study and Drug Repurposing
title_short Zika M—A Potential Viroporin: Mutational Study and Drug Repurposing
title_sort zika m—a potential viroporin: mutational study and drug repurposing
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8944957/
https://www.ncbi.nlm.nih.gov/pubmed/35327443
http://dx.doi.org/10.3390/biomedicines10030641
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