In-silico molecular design approach of some phytoconstituents from Nardostachys jatamansi as HIV/AIDS agents

Nardostachys jatamansi, a small rhizomatous herb from the Valerianaceae family, has been traditionally used in Ayurveda for neurological and gastrointestinal disorders. However, its rising demand and extensive use have led to overharvesting, placing the species at risk of extinction. This study explores the therapeutic potential of N. jatamansi phytoconstituents through in-silico evaluation as antiviral agents targeting HIV-1 reverse transcriptase. The 3D structure of HIV-1 RT (PDB ID: 6KJV) was validated through Ramachandran plot, ERRAT, and PROCHECK analysis, confirming its suitability for docking studies. Fifteen ligands from N. jatamansi and the standard drug Doravirine were evaluated for biological activity, ATC classification, ADMET properties, HIV-1 RT inhibition, and docking performance. All compounds adhered to Lipinski's rule, exhibited favorable absorption, metabolism, and clearance, and showed minimal toxicity. Antiviral prediction through HIVprotI indicated significant inhibitory activity against HIV-1 RT. Notably, compounds 10, 13, and 14 showed docking scores (-8.6 to - 8.0 kcal/mol) comparable to Doravirine (-8.9 kcal/mol), suggesting strong binding affinity and potential reverse transcriptase inhibition. Furthermore, the calculated therapeutic index highlighted compounds 10, 13, and 14 as having notable therapeutic promise. Among these, compound 10 showed the highest therapeutic potential, exhibiting a therapeutic index value of 36.32. These findings support the therapeutic relevance of N. jatamansi-derived compounds and warrant further in-vitro and in-vivo studies to explore their role as novel antiretroviral agents.