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Targeting envelope proteins of poxviruses to repurpose phytochemicals against monkeypox: An in silico investigation

The monkeypox virus (MPXV) has become a major threat due to the increasing global caseload and the ongoing multi-country outbreak in non-endemic territories. Due to limited research in this avenue and the lack of intervention strategies, the present study was aimed to virtually screen bioactive phyt...

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Autores principales: Gulati, Pallavi, Chadha, Jatin, Harjai, Kusum, Singh, Sandeepa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9849581/
https://www.ncbi.nlm.nih.gov/pubmed/36687601
http://dx.doi.org/10.3389/fmicb.2022.1073419
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author Gulati, Pallavi
Chadha, Jatin
Harjai, Kusum
Singh, Sandeepa
author_facet Gulati, Pallavi
Chadha, Jatin
Harjai, Kusum
Singh, Sandeepa
author_sort Gulati, Pallavi
collection PubMed
description The monkeypox virus (MPXV) has become a major threat due to the increasing global caseload and the ongoing multi-country outbreak in non-endemic territories. Due to limited research in this avenue and the lack of intervention strategies, the present study was aimed to virtually screen bioactive phytochemicals against envelope proteins of MPXV via rigorous computational approaches. Molecular docking, molecular dynamic (MD) simulations, and MM/PBSA analysis were used to investigate the binding affinity of 12 phytochemicals against three envelope proteins of MPXV, viz., D13, A26, and H3. Silibinin, oleanolic acid, and ursolic acid were computationally identified as potential phytochemicals that showed strong binding affinity toward all the tested structural proteins of MPXV through molecular docking. The stability of the docked complexes was also confirmed by MD simulations and MM/PBSA calculations. Results from the iMODS server also complemented the findings from molecular docking and MD simulations. ADME analysis also computationally confirmed the drug-like properties of the phytochemicals, thereby asserting their suitability for consumption. Hence, this study envisions the candidature of bioactive phytochemicals as promising inhibitors against the envelope proteins of the MPXV, serving as template molecules that could further be experimentally evaluated for their efficacy against monkeypox.
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spelling pubmed-98495812023-01-20 Targeting envelope proteins of poxviruses to repurpose phytochemicals against monkeypox: An in silico investigation Gulati, Pallavi Chadha, Jatin Harjai, Kusum Singh, Sandeepa Front Microbiol Microbiology The monkeypox virus (MPXV) has become a major threat due to the increasing global caseload and the ongoing multi-country outbreak in non-endemic territories. Due to limited research in this avenue and the lack of intervention strategies, the present study was aimed to virtually screen bioactive phytochemicals against envelope proteins of MPXV via rigorous computational approaches. Molecular docking, molecular dynamic (MD) simulations, and MM/PBSA analysis were used to investigate the binding affinity of 12 phytochemicals against three envelope proteins of MPXV, viz., D13, A26, and H3. Silibinin, oleanolic acid, and ursolic acid were computationally identified as potential phytochemicals that showed strong binding affinity toward all the tested structural proteins of MPXV through molecular docking. The stability of the docked complexes was also confirmed by MD simulations and MM/PBSA calculations. Results from the iMODS server also complemented the findings from molecular docking and MD simulations. ADME analysis also computationally confirmed the drug-like properties of the phytochemicals, thereby asserting their suitability for consumption. Hence, this study envisions the candidature of bioactive phytochemicals as promising inhibitors against the envelope proteins of the MPXV, serving as template molecules that could further be experimentally evaluated for their efficacy against monkeypox. Frontiers Media S.A. 2023-01-05 /pmc/articles/PMC9849581/ /pubmed/36687601 http://dx.doi.org/10.3389/fmicb.2022.1073419 Text en Copyright © 2023 Gulati, Chadha, Harjai and Singh. 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 Microbiology
Gulati, Pallavi
Chadha, Jatin
Harjai, Kusum
Singh, Sandeepa
Targeting envelope proteins of poxviruses to repurpose phytochemicals against monkeypox: An in silico investigation
title Targeting envelope proteins of poxviruses to repurpose phytochemicals against monkeypox: An in silico investigation
title_full Targeting envelope proteins of poxviruses to repurpose phytochemicals against monkeypox: An in silico investigation
title_fullStr Targeting envelope proteins of poxviruses to repurpose phytochemicals against monkeypox: An in silico investigation
title_full_unstemmed Targeting envelope proteins of poxviruses to repurpose phytochemicals against monkeypox: An in silico investigation
title_short Targeting envelope proteins of poxviruses to repurpose phytochemicals against monkeypox: An in silico investigation
title_sort targeting envelope proteins of poxviruses to repurpose phytochemicals against monkeypox: an in silico investigation
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9849581/
https://www.ncbi.nlm.nih.gov/pubmed/36687601
http://dx.doi.org/10.3389/fmicb.2022.1073419
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