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Molecular Dynamics Study on Selected Bioactive Phytochemicals as Potential Inhibitors of HIV-1 Subtype C Protease
Acquired immunodeficiency syndrome (AIDS), one of the deadliest global diseases, is caused by the Human Immunodeficiency Virus (HIV). To date, there are no known conventional drugs that can cure HIV/AIDS, and this has prompted continuous scientific efforts in the search for novel and potent anti-HIV...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9695624/ https://www.ncbi.nlm.nih.gov/pubmed/36422295 http://dx.doi.org/10.3390/metabo12111155 |
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author | Shode, Francis Oluwole Uhomoibhi, John Omo-osagie Idowu, Kehinde Ademola Sabiu, Saheed Govender, Krishna Kuben |
author_facet | Shode, Francis Oluwole Uhomoibhi, John Omo-osagie Idowu, Kehinde Ademola Sabiu, Saheed Govender, Krishna Kuben |
author_sort | Shode, Francis Oluwole |
collection | PubMed |
description | Acquired immunodeficiency syndrome (AIDS), one of the deadliest global diseases, is caused by the Human Immunodeficiency Virus (HIV). To date, there are no known conventional drugs that can cure HIV/AIDS, and this has prompted continuous scientific efforts in the search for novel and potent anti-HIV therapies. In this study, molecular dynamics simulation (MDS) and computational techniques were employed to investigate the inhibitory potential of bioactive compounds from selected South African indigenous plants against HIV-1 subtype C protease (HIVpro). Of the eight compounds (CMG, MA, UA, CA, BA, UAA, OAA and OA) evaluated, only six (CMG (−9.9 kcal/mol), MA (−9.3 kcal/mol), CA (−9.0 kcal/mol), BA (−8.3 kcal/mol), UAA (−8.5 kcal/mol), and OA (−8.6 kcal/mol)) showed favourable activities against HIVpro and binding landscapes like the reference FDA-approved drugs, Lopinavir (LPV) and Darunavir (DRV), with CMG and MA having the highest binding affinities. Using the structural analysis (root-mean-square deviation (RMSD), fluctuation (RMSF), and radius of gyration (RoG) of the bound complexes with HIVpro after 350 ns, structural evidence was observed, indicating that the six compounds are potential lead candidates for inhibiting HIVpro. This finding was further corroborated by the structural analysis of the enzyme–ligand complexe systems, where structural mechanisms of stability, flexibility, and compactness of the study metabolites were established following binding with HIVpro. Furthermore, the ligand interaction plots revealed that the metabolites interacted hydrophobically with the active site amino residues, with identification of other key residues implicated in HIVpro inhibition for drug design. Overall, this is the first computational report on the anti-HIV-1 activities of CMG and MA, with efforts on their in vitro and in vivo evaluations underway. Judging by the binding affinity, the degree of stability, and compactness of the lead metabolites (CMG, MA, CA, BA, OA, and UAA), they could be concomitantly explored with conventional HIVpro inhibitors in enhancing their therapeutic activities against the HIV-1 serotype. |
format | Online Article Text |
id | pubmed-9695624 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96956242022-11-26 Molecular Dynamics Study on Selected Bioactive Phytochemicals as Potential Inhibitors of HIV-1 Subtype C Protease Shode, Francis Oluwole Uhomoibhi, John Omo-osagie Idowu, Kehinde Ademola Sabiu, Saheed Govender, Krishna Kuben Metabolites Article Acquired immunodeficiency syndrome (AIDS), one of the deadliest global diseases, is caused by the Human Immunodeficiency Virus (HIV). To date, there are no known conventional drugs that can cure HIV/AIDS, and this has prompted continuous scientific efforts in the search for novel and potent anti-HIV therapies. In this study, molecular dynamics simulation (MDS) and computational techniques were employed to investigate the inhibitory potential of bioactive compounds from selected South African indigenous plants against HIV-1 subtype C protease (HIVpro). Of the eight compounds (CMG, MA, UA, CA, BA, UAA, OAA and OA) evaluated, only six (CMG (−9.9 kcal/mol), MA (−9.3 kcal/mol), CA (−9.0 kcal/mol), BA (−8.3 kcal/mol), UAA (−8.5 kcal/mol), and OA (−8.6 kcal/mol)) showed favourable activities against HIVpro and binding landscapes like the reference FDA-approved drugs, Lopinavir (LPV) and Darunavir (DRV), with CMG and MA having the highest binding affinities. Using the structural analysis (root-mean-square deviation (RMSD), fluctuation (RMSF), and radius of gyration (RoG) of the bound complexes with HIVpro after 350 ns, structural evidence was observed, indicating that the six compounds are potential lead candidates for inhibiting HIVpro. This finding was further corroborated by the structural analysis of the enzyme–ligand complexe systems, where structural mechanisms of stability, flexibility, and compactness of the study metabolites were established following binding with HIVpro. Furthermore, the ligand interaction plots revealed that the metabolites interacted hydrophobically with the active site amino residues, with identification of other key residues implicated in HIVpro inhibition for drug design. Overall, this is the first computational report on the anti-HIV-1 activities of CMG and MA, with efforts on their in vitro and in vivo evaluations underway. Judging by the binding affinity, the degree of stability, and compactness of the lead metabolites (CMG, MA, CA, BA, OA, and UAA), they could be concomitantly explored with conventional HIVpro inhibitors in enhancing their therapeutic activities against the HIV-1 serotype. MDPI 2022-11-21 /pmc/articles/PMC9695624/ /pubmed/36422295 http://dx.doi.org/10.3390/metabo12111155 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 Shode, Francis Oluwole Uhomoibhi, John Omo-osagie Idowu, Kehinde Ademola Sabiu, Saheed Govender, Krishna Kuben Molecular Dynamics Study on Selected Bioactive Phytochemicals as Potential Inhibitors of HIV-1 Subtype C Protease |
title | Molecular Dynamics Study on Selected Bioactive Phytochemicals as Potential Inhibitors of HIV-1 Subtype C Protease |
title_full | Molecular Dynamics Study on Selected Bioactive Phytochemicals as Potential Inhibitors of HIV-1 Subtype C Protease |
title_fullStr | Molecular Dynamics Study on Selected Bioactive Phytochemicals as Potential Inhibitors of HIV-1 Subtype C Protease |
title_full_unstemmed | Molecular Dynamics Study on Selected Bioactive Phytochemicals as Potential Inhibitors of HIV-1 Subtype C Protease |
title_short | Molecular Dynamics Study on Selected Bioactive Phytochemicals as Potential Inhibitors of HIV-1 Subtype C Protease |
title_sort | molecular dynamics study on selected bioactive phytochemicals as potential inhibitors of hiv-1 subtype c protease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9695624/ https://www.ncbi.nlm.nih.gov/pubmed/36422295 http://dx.doi.org/10.3390/metabo12111155 |
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