In silico screening, pharmacokinetic, DFT, and dynamics simulation study of ant-hepatitis C virus compounds as potential NS5B Polymerase inhibitors

Abstract

Cirrhosis, hepatocellular carcinoma, and other serious liver diseases are caused by the hepatitis C virus (HCV) infection. An oral NS5B inhibitor for the therapy of HCV called Sofosbuvir has received approval. However, its high cost and numerous side effects are emphasized. Therefore, alternative HCV cures that are affordable and side-effect-free must be explored. This research aimed at screening novel bioactive plant molecules as potent HCV inhibitors from databases by exploring the drug kinetic model through the molecular docking, ADMET prediction, density functional theory (DFT) and dynamics simulation approach to identify lead compounds and gave insight into the mechanism of its reaction. The findings indicated that 4 out of 80 screened compounds were chosen as active candidate hits with the most active molecule having PubChem CID 5280445 which is Flavonoid isolated from Eclipta alba displaying the best pharmacokinetics characteristics and kinetic potency as compared with the standard drug sofosbuvir. The compounds' recommendation for a confirmatory biological evaluation was prompted by the predictive kinetic analysis's further justification of the compounds as potential hit molecules through molecular dynamics (MD) with the variable analyzed pointing out the stability of the complexes.