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Drug repurposing approach against chikungunya virus: an in vitro and in silico study

The chikungunya virus (CHIKV) is an alphavirus transmitted by Aedes mosquitoes. There are no licenced antivirals or vaccines for treatment or prevention. Drug repurposing approach has emerged as a novel concept to find alternative uses of therapeutics to battle pathogens. In the present study, anti...

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Autores principales: Kasabe, Bhagyashri, Ahire, Gunwant, Patil, Poonam, Punekar, Madhura, Davuluri, Kusuma Sai, Kakade, Mahadeo, Alagarasu, Kalichamy, Parashar, Deepti, Cherian, Sarah
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10174255/
https://www.ncbi.nlm.nih.gov/pubmed/37180434
http://dx.doi.org/10.3389/fcimb.2023.1132538
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author Kasabe, Bhagyashri
Ahire, Gunwant
Patil, Poonam
Punekar, Madhura
Davuluri, Kusuma Sai
Kakade, Mahadeo
Alagarasu, Kalichamy
Parashar, Deepti
Cherian, Sarah
author_facet Kasabe, Bhagyashri
Ahire, Gunwant
Patil, Poonam
Punekar, Madhura
Davuluri, Kusuma Sai
Kakade, Mahadeo
Alagarasu, Kalichamy
Parashar, Deepti
Cherian, Sarah
author_sort Kasabe, Bhagyashri
collection PubMed
description The chikungunya virus (CHIKV) is an alphavirus transmitted by Aedes mosquitoes. There are no licenced antivirals or vaccines for treatment or prevention. Drug repurposing approach has emerged as a novel concept to find alternative uses of therapeutics to battle pathogens. In the present study, anti CHIKV activity of fourteen FDA-approved drugs was investigated by in vitro and in silico approaches. Focus-forming unit assay, immunofluorescence test, and quantitative RT-PCR assay were used to assess the in vitro inhibitory effect of these drugs against CHIKV in Vero CCL-81 cells. The findings showed that nine compounds, viz., temsirolimus, 2-fluoroadenine, doxorubicin, felbinac, emetine, lomibuvir, enalaprilat, metyrapone and resveratrol exhibit anti chikungunya activity. Furthermore, in silico molecular docking studies performed by targeting CHIKV structural and non-structural proteins revealed that these drugs can bind to structural protein targets such as envelope protein, and capsid, and non-structural proteins NSP2, NSP3 and NSP4 (RdRp). Findings from in vitro and in silico studies reveal that these drugs can suppress the infection and replication of CHIKV and further in vivo studies followed by clinical trials are warranted.
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spelling pubmed-101742552023-05-12 Drug repurposing approach against chikungunya virus: an in vitro and in silico study Kasabe, Bhagyashri Ahire, Gunwant Patil, Poonam Punekar, Madhura Davuluri, Kusuma Sai Kakade, Mahadeo Alagarasu, Kalichamy Parashar, Deepti Cherian, Sarah Front Cell Infect Microbiol Cellular and Infection Microbiology The chikungunya virus (CHIKV) is an alphavirus transmitted by Aedes mosquitoes. There are no licenced antivirals or vaccines for treatment or prevention. Drug repurposing approach has emerged as a novel concept to find alternative uses of therapeutics to battle pathogens. In the present study, anti CHIKV activity of fourteen FDA-approved drugs was investigated by in vitro and in silico approaches. Focus-forming unit assay, immunofluorescence test, and quantitative RT-PCR assay were used to assess the in vitro inhibitory effect of these drugs against CHIKV in Vero CCL-81 cells. The findings showed that nine compounds, viz., temsirolimus, 2-fluoroadenine, doxorubicin, felbinac, emetine, lomibuvir, enalaprilat, metyrapone and resveratrol exhibit anti chikungunya activity. Furthermore, in silico molecular docking studies performed by targeting CHIKV structural and non-structural proteins revealed that these drugs can bind to structural protein targets such as envelope protein, and capsid, and non-structural proteins NSP2, NSP3 and NSP4 (RdRp). Findings from in vitro and in silico studies reveal that these drugs can suppress the infection and replication of CHIKV and further in vivo studies followed by clinical trials are warranted. Frontiers Media S.A. 2023-04-27 /pmc/articles/PMC10174255/ /pubmed/37180434 http://dx.doi.org/10.3389/fcimb.2023.1132538 Text en Copyright © 2023 Kasabe, Ahire, Patil, Punekar, Davuluri, Kakade, Alagarasu, Parashar and Cherian https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Kasabe, Bhagyashri
Ahire, Gunwant
Patil, Poonam
Punekar, Madhura
Davuluri, Kusuma Sai
Kakade, Mahadeo
Alagarasu, Kalichamy
Parashar, Deepti
Cherian, Sarah
Drug repurposing approach against chikungunya virus: an in vitro and in silico study
title Drug repurposing approach against chikungunya virus: an in vitro and in silico study
title_full Drug repurposing approach against chikungunya virus: an in vitro and in silico study
title_fullStr Drug repurposing approach against chikungunya virus: an in vitro and in silico study
title_full_unstemmed Drug repurposing approach against chikungunya virus: an in vitro and in silico study
title_short Drug repurposing approach against chikungunya virus: an in vitro and in silico study
title_sort drug repurposing approach against chikungunya virus: an in vitro and in silico study
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10174255/
https://www.ncbi.nlm.nih.gov/pubmed/37180434
http://dx.doi.org/10.3389/fcimb.2023.1132538
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