Anti-HCV NS2-3 potential of selected plant bioactive compounds revealed by docking, simulation and DFT

Presently, there is no vaccine for hepatitis C virus (HCV) and available drugs present with adverse effects that have prompted the search for newer and safer alternatives. The present study evaluated the anti-HCV potential of selected bioactive compounds from Jatropha tanjorensis and Solanum nigrum against HCV non-structural (NS2-3) protein. The selected bioactive compounds (3-methoxy-4-methylaniline, 2,2'-Azoxybis[3-methylpyridine], isopropyl thiophosphondiamide, and squalene) were screened for compliance with Lipinski's role five (LRF) and toxicity using the MCULE tool. Furthermore, the ligands were docked against the NS2-3 (2hd0) protein with ledipasvir, and a co-crystal as controls using the Autodock Vina tool. Docking scores were generated using the London dG scoring function. Following docking, a 200 nanosecond (nsec) simulation run was performed using the Schrodinger Desmond module. In addition, density functional theory (DFT) was utilised to evaluate their reactivities. The selected compounds were not toxic and obeyed the LRF. Molecular docking scores for ledipasvir and the co-crystal were - 8.8 and - 6.3 kcal/mol, respectively while of the ligands ranged from - 3.5 to -7.3 kcal/mol, implying favourable bindings. The amino acid residues involved in the binding were those within the active site of the target protein. RMSD values indicated that isopropyl thiophosphondiamide was the most stable ligand. PSA, MolSA and SASA values suggest stability and availability for water contact. DFT calculations indicate that the compounds were moderately stable and highly reactive, with energy gaps that ranged from 0.5810 to 1.0621 eV. The favourable pharmacokinetics and docking outputs observed in this study needs to be further validated using in vitro and in vivo studies.