Combined quantum-chemical and in silico molecular docking studies on some phytomedicinal compounds reveal potential anti-HIV leads

Abstract

The human immunodeficiency virus (HIV) continues to be a global health challenge, with the emergence of drugresistant strains highlighting the urgent need for novel therapeutics. Present work sought to examine natural diterpenoid compounds as prospective anti-HIV drugs with the objective of identifying safe and effective inhibitors that target essential HIV enzymes and viral entry mechanisms. In this study, four natural diterpenoid compounds, Onishibarin A and B (from Daphne pseudomezereum) and Abietamethinol C and D (from Isodon amethystoides) were selected based on literature survey for an integrative in silico structural and functional validation of their anti-HIV activities. A comprehensive cheminformatics approach involving quantum chemical calculations, in silico ADMET profiling, and molecular docking was employed to investigate their pharmacological potential. Geometry optimizations and reactivity descriptors were computed using density functional theory (DFT) at the B3LYP/6-31G (d,p) level to analyze their stability and electronic behavior. Global and local reactivity indices, including frontier molecular orbital energies, Fukui functions, and electrophilicity descriptors, were used to predict reactive sites and antiradical potential. ADMET assessments using SwissADME and ProTox-3.0 indicated favourable drug-likeness, low toxicity, and compliance with Lipinski’s and Veber’s rules. Molecular docking against HIV-1 Reverse Transcriptase (PDB ID: 3DLE) and HIV-1 gp120 Envelope Glycoprotein (PDB ID: 4RZ8) revealed strong binding affinities, especially for Onishibarin A, suggesting potential inhibitory action. Collectively, these findings support the therapeutic promise of these natural diterpenoids as leads for anti-HIV drug development and highlight the utility of integrated computational approaches in natural product-based drug discovery.