title: Binding mode prediction of biologically active compounds from plant Salvia Miltiorrhiza as integrase inhibitor.
abstract: Integrase (IN), an essential enzyme for HIV-1 replication, has been targeted in antiretroviral drug therapy. The emergence of HIV-1 variants 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 were determined using molecular docking calculation. Both M522 and M532 displayed similar modes of binding within the IN putative binding pocket and exhibited favorable interactions with the catalytic Mg(2+) ions, the nearby amino acids and viral DNA through metal-ligand chelation, hydrogen bonding and π-π stacking interactions. Furthermore, the modes of action of these two compounds against the mutated Y212R, N224H and S217H PFV IN were also predicted. Although the replacement of amino acid could somehow 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 against drug resistant strains.
authors.affiliation: Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Mahasarakham University, Mahasarakham,44150, Thailand.
authors.forename: Nadtanet
authors.initials: N
authors.lastname: Nunthaboot
authors.forename: Kiattisak
authors.initials: K
authors.lastname: Lugsanangarm
authors.forename: Sirirat
authors.initials: S
authors.lastname: Kokpol
authors.forename: Ibrahim S
authors.initials: IS
authors.lastname: Abd-Elazem
keywords: Docking; Drug resistance; Integrase; Mutation