Hepatitis C virus causes several liver disorders worldwide. Various anti-viral medications treat hepatitis C by targeting HCV's cell cycle. HCV replication and RNA synthesis need NS5B. It's a proven antiviral target. HCV medication discovery targets NS5B protein. This study used in silico methods to explore medicinal plant phytochemicals against HCV NS5B polymerase. Total of 100 phytochemicals derived from Cichorium intybus, Saussurea lappa, Trigonella foenum-graecum, Glycin max, Lepidium sativum and Nigella sativa were selected and their structures were retrieved from PubChem database. These phytochemicals were passed through filters including Lipinski’s rule of 5, toxicity filter, blood brain barrier and TPSA for bioactive profiling. Molecular docking determined phytochemical interaction patterns. Molecular dynamics simulation evaluated docked complex structure stability in receptor binding sites. 6'-O-acetyl daidzin, coumestrol and hederagenin have shown common molecular interaction with Asn291 and Asp318 of HCV NS5B, which are crucial residues to block Hepatitis C virus activity and growth. These phytochemicals also shown low RMSD values in md simulation making them structural stable inside the binding pocket of HCV N5SB. Based on pharmacological properties, structural stability, and target receptor active site, these phytochemicals are suitable herbal treatment of Hepatitis C both in vitro and clinical trials. Hence, 6'-O-acetyl daidzin, coumestrol and hederagenin are found to be most effective phytochemicals due to their comparatively high binding affinity values with NS5B protein of HCV besides their higher binding affinity values than reference drug sofosbuvir. It is recommended to investigate these possible pharmacological hits in vitro and pre-clinically to treat hepatitis C.

Keywords: Molecular modeling, virtual screening, antiviral agents, bioactive compounds, herbal medicine, protein-ligand interaction, viral NS5B protein.