ETHNOPHARMACOLOGICAL VALIDATION AND COMPUTATIONAL SCREENING OF MADHYA PRADESH MEDICINAL PLANTS AS MULTI-TARGET HIV-1 INHIBITORS WITH PREDICTED BLOOD-BRAIN BARRIER PERMEABILITY FOR NEURO-HIV THERAPY

Based on comprehensive multi-parameter scoring integrating docking affinity, molecular dynamics stability, BBB permeability, and drug-likeness, three compounds emerged as Priority 1 candidates warranting immediate experimental validation: curcumin from C. longa demonstrating superior RT inhibition with stable MD trajectories and excellent BBB+ profile; andrographolide from A. paniculata showing potent protease inhibition comparable to saquinavir; and eugenol from O. sanctum exhibiting moderate multi-target activity with exceptional BBB permeability and high oral bioavailability. Priority 2 candidates requiring further optimization included berberine (good integrase inhibition with CYP/P-gp concerns), withaferin A (good multi-target activity but BBB- and toxicity issues), and ursolic acid (moderate activity with good safety profile). Priority 3 compounds including demethoxycurcumin, palmatine, and phyllanthin demonstrated moderate activity but were limited by lower abundance, toxicity concerns, or poor BBB permeability, suggesting derivatization may be required for therapeutic development. This comprehensive phytochemical profiling of six medicinal plants from Madhya Pradesh biodiversity hotspots revealed exceptionally high concentrations of bioactive compounds including curcumin (124 mg/g) and andrographolide (78 mg/g) exceeding national averages, with curcumin demonstrating significantly higher reverse transcriptase binding affinity (-9.8 kcal/mol) than efavirenz (-8.2 kcal/mol, d=2.1, p<0.001) and multi-target inhibition across all three HIV enzymes, while twelve phytochemicals (43%) showed superior blood-brain barrier permeability compared to only 30% of standard ART drugs (OR=3.12, p=0.002), with curcumin, andrographolide, and eugenol emerging as priority neuro-HIV therapeutic leads that validate traditional tribal uses and warrant immediate experimental validation through enzyme assays and in vivo studies, though formulation challenges for curcumin require nanoparticle strategies for clinical translation toward CNS-directed HIV therapy.

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