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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.
Afiliação
  • Shode FO; Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban University of Technology (DUT), P.O. Box 1334, Durban 4000, South Africa.
  • Uhomoibhi JO; Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban University of Technology (DUT), P.O. Box 1334, Durban 4000, South Africa.
  • Idowu KA; Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban University of Technology (DUT), P.O. Box 1334, Durban 4000, South Africa.
  • Sabiu S; Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban University of Technology (DUT), P.O. Box 1334, Durban 4000, South Africa.
  • Govender KK; Department of Chemical Sciences, University of Johannesburg, Doornfontein Campus, P.O. Box 17011, Johannesburg 2028, South Africa.
Metabolites ; 12(11)2022 Nov 21.
Article em En | MEDLINE | ID: mdl-36422295
ABSTRACT
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.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2022 Tipo de documento: Article