Background: HIV-1 reverse transcriptase (RT) and protease (PR) are primary targets for antiretroviral therapy. Natural phytochemicals from medicinal plants offer diverse chemical scaffolds for inhibiting these enzymes. This study evaluated the binding potential of curcumin, ursolic acid, quercetin, berberine, and andrographolide against HIV-1 RT and PR using molecular docking.

Methods: Molecular docking was performed against HIV-1 RT (PDB: 1REV) and HIV-1 protease (PDB: 1EBY) using AutoDockVina. Binding affinities, hydrogen bonding patterns, hydrophobic interactions, and π-π stacking were analyzed. Binding poses were visualized using Discovery Studio. ADMET properties were predicted using SwissADME.

Results: Curcumin demonstrated the highest binding affinity against RT (-11.5 kcal/mol) forming four hydrogen bonds with Lys101, Tyr181, Tyr188, and Asp185. Ursolic acid showed the highest binding against protease (-10.8 kcal/mol) with hydrophobic contacts to Asp25, Asp29, Ile50, and Ile84. Quercetin showed multi-target activity with -10.2 kcal/mol against integrase (from previous study) and -9.5 kcal/mol against RT. Berberine showed -9.3 kcal/mol against RT with electrostatic interactions. Andrographolide showed -8.5 kcal/mol against gp120. All compounds exhibited low toxicity and favorable drug-likeness.

Conclusion: Curcumin is the most potent RT inhibitor. Ursolic acid is the most potent protease inhibitor. Quercetin shows promising multi-target activity. These findings warrant in vitro validation through enzymatic inhibition assays.

Keywords: HIV-1 reverse transcriptase, HIV-1 protease, curcumin, ursolic acid, quercetin, molecular docking