Evaluation of Various Bioactive Molecules for Their Gp120-CD4 Binding Inhibitory Properties by In-silico Molecular Docking and Dynamic Studies

Acquired immunodeficiency syndrome (AIDS), caused by the human immunodeficiency virus (HIV), remains a significant global health challenge, affecting over 38.4 million individuals worldwide according to the World Health Organization (WHO). The high mutation rate of HIV complicates the effectiveness of conventional antiviral drugs, necessitating novel therapeutic approaches. A critical step in HIV infection is the interaction between the viral envelope protein gp120 and CD4+ receptors on host cells, making gp120 an attractive therapeutic target. This study aimed to identify potential inhibitors that disrupt the gp120-CD4 interaction through computational methods. Using an integrated approach combining multiple sequence alignment, phylogenetic analysis, structure prediction, ADME analysis, Molecular docking studies and toxicity profiling identified Epigallocatechin gallate (EGCG) as a promising lead inhibitor of the gp120-CD4 interaction, with a binding affinity of - 6.378 kcal/mol. The stability of the gp120-EGCG complex was validated through 100 ns molecular dynamics simulations and free binding energy calculations, where ΔGBind was calculated to be - 69.7 04 ± 37.940 kJ/mol. EGCG demonstrated favourable drug-like properties with no significant toxicity concerns in our computational analysis. These findings provide a foundation for future in vitro and in vivo studies to develop EGCG-based HIV entry inhibitors.