Binding mode prediction of biologically active compounds from plant Salvia Miltiorrhiza as integrase inhibitor |
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| Authors: | Nadtanet Nunthaboot Kiattisak Lugsanangarm Sirirat Kokpol Ibrahim S Abd-Elazem |
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| Affiliation: | 1.Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Mahasarakham University, Mahasarakham,44150, Thailand;2.Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand;3.Department of Biology, The Johns Hopkins University, Baltimore, Maryland, 21218, USA |
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| Abstract: | Integrase (IN), an essential enzyme for HIV-1 replication, has been targeted in antiretroviral drug therapy. The emergence of HIV-1variants clinically resistant to antiretroviral agents has lead to the development of alternative IN inhibitors. In the present work,binding modes of a high potent IN inhibitor, M522 and M532, within the catalytic binding site of wild type (WT) IN weredetermined using molecular docking calculation. Both M522 and M532 displayed similar modes of binding within the IN putativebinding pocket and exhibited favorable interactions with the catalytic Mg2+ ions, the nearby amino acids and viral DNA throughmetal-ligand chelation, hydrogen bonding and π-π stacking interactions. Furthermore, the modes of action of these two compoundsagainst the mutated Y212R, N224H and S217H PFV IN were also predicted. Although the replacement of amino acid couldsomehow disturb inhibitor binding mode, almost key interactions which detected in the WT complexes were fairly conserved.Detailed information could highlight the application of M522 and M532 as candidate IN inhibitors for drug development againstdrug resistant strains. |
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| Keywords: | Integrase Docking Drug resistance Mutation |
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