Evaluating Allium lycaonicum Phytochemicals as CCR5 Inhibitors for HIV Therapy: A Computational Study.

CCR5 is a G protein-coupled receptor and a key therapeutic target for human immunodeficiency virus (HIV)-mediated infections, including acquired immunodeficiency syndrome (AIDS). Studies have demonstrated the therapeutic potential of bioactive compounds from ethnomedicinal plants in inhibiting HIV pathogenesis. This study aimed to identify the molecular mechanisms underlying the therapeutic activity of ethnomedicinal phytochemicals against CCR5 through an in silico approach. Molecular docking analysis was conducted using Glide tool of Maestro v12.5. The protein-ligand 3D interactions were modeled and evaluated by structural interaction fingerprinting (SIFt) analysis. ADMET properties of the ligands were assessed separately using SwissADME, pkCSM, and STopTox servers. The geometric parameters of the complexes were determined using density functional theory (DFT) computations. The validated docking protocol yielded a reliable re-docking score of -10.464. Hydroxyl groups and benzene ring π-stacking were identified as contributing to the stability of the complexes. Furthermore, Thr105, Glu283, and Cys178 were observed as key H-bond-accepting residues in phytochemicals against CCR5 receptors. Mol_22 is least toxic, followed by Mol_24 and Mol-31. DFT analysis of Mol-22 revealed its high dipole moments, lower energy gaps, and strong electrophilicity, which was further validated by molecular dynamics (MD) simulations. This study revealed that Mol_22 exhibits acceptable pharmacokinetic features as a potential therapeutic agent for CCR5 inhibition in HIV management.