The human immunodeficiency virus (HIV) is the cause of acquired immunodeficiency syndrome, or AIDS, which has been a serious global health concern since its discovery in 1981. Finding novel treatment leads is crucial, as seen by the lack of effective antiretroviral drugs. To identify potential HIV-1 proteins, this study employed a technique known as pharmacophore-based virtual screening and molecular docking. Using a pharmacophore model that was created, compounds from DrugBank and an internal library of Philippine natural products were screened before being docked onto the crystal structure of HIV-1 protease. The top 10 hits that were selected for further analysis included seven-methyl-GpppA, remikiren, clomocycline, metrizamide, SC-74020, and 6-(4-{[2-(3-iodobenzyl)-3-oxocyclohex-1-en-1-yl]amino}phenyl). ~(4Z) 5-methyl-4,5-dihydropyridazin-3(2H) -one -2-[(1R,2R)-1-amino-2-hydroxypropyl] -4-[(4-amino-1H-indol-3-yl)methylene] 5-oxo-4,5-dihydro-1H-imidazol-1-ylacetic acid, bevantolol, and two natural chemicals called quercetin 3-O-β-D-(2-O-galloyl-β-D-glucopyranosyl) 4-O-vinylpropionate with vitamin C together. Predicted ADMET characteristics and docking data showed that SC-74020 was the most promising inhibitor. 6-(4-{[2-(3-iodobenzyl)-3-oxocyclohex-1-en-1-yl]amino~phenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one was the second-place pyridazinone derivative. These results identify potential lead compounds for further in vitro and in vivo testing in the development of novel HIV-1 protease inhibitors.
