Targeting Multiple Hepatitis C Virus Proteins with Lignans from the Piper Genus: A Molecular Docking and Dynamics Study

Hepatitis is an inflammatory liver disease primarly caused by viral infections, including hepatitis A, B, C, D, and E viruses. Among these, hepatitis C virus (HCV) is of particular concern due to its high rate of chronic infection, which often progresses to cirrhosis and hepatocellular carcinoma. Despite the availability of direct-acting antivirals (DAAs), high treatment costs and the absence of a vaccine remain major barriers to global HCV eradication. This study aimed to identify potential anti-HCV compounds from lignan metabolites of the Piper genus. Molecular docking followed by molecular dynamics (MD) simulations was used to evaluate evaluate ligand binding to multiple HCV protein targets. Screening of the lignan metabolites revealed three 'hit' compounds compared to the reference drug on the Hepatitis C virus non-structural protein 3 (NS3), Hepatitis C virus non-structural protein 5B (NS5B), Hepatitis C virus envelope glycoprotein E1 (E1), and Hepatitis C virus envelope glycoprotein E2 (E2) receptors: Piperbonamide A (-57.20 kcal/mol), Dipiperamide D (-56.97 &-72.87 kcal/mol), and Ferrudiol (-70.77 kcal/mol). Subsequently, MD simulations revealed the Ferrudiol-E2 complex maintained consistently low root mean square deviation (RMSD) values (