Regulation of NS5B Polymerase Activity of Hepatitis C Virus by Target Specific Phytotherapeutics: An In-Silico Molecular Dynamics Approach.

Abstract

Chronic hepatitis caused by the hepatitis C virus (HCV) is closely linked with the advancement of liver disease. The research hypothesis suggests that the NS5B enzyme (non-structural 5B protein) of HCV plays a pivotal role in facilitating viral replication within host cells. Hence, the objective of the present investigation is to identify the binding interactions between the structurally diverse phytotherapeutics and those of the catalytic residue of the target NS5B polymerase protein. Results of our docking simulations reveal that compounds such as arjunolic acid, sesamin, arjungenin, astragalin, piperic acid, piperidine, piperine, acalyphin, adhatodine, amyrin, anisotine, apigenin, cuminaldehyde, and curcumin exhibit a maximum of three interactions with the catalytic residues (Asp 220, Asp 318, and Asp 319) present on the Hepatitis C virus NS5B polymerase of HCV. Molecular dynamic simulation, particularly focusing on the best binding lead compound, arjunolic acid (-8.78 kcal/mol), was further extensively analyzed using RMSD, RMSF, Rg, and SASA techniques. The results of the MD simulation confirm that the NS5B-arjunolic acid complex becomes increasingly stable from 20 to 100 ns. The orientation of both arjunolic acid and sofosbuvir triphosphate (standard) within the active site was investigated through DCCM, PCA, and FEL analysis, indicating highly stable interactions of the lead arjunolic acid with the catalytic region of the NS5B enzyme. The findings of our current investigation suggest that bioactive therapeutics like arjunolic acid could serve as promising candidates for limiting the NS5B polymerase activity of the hepatitis C virus, offering hope for the future of HCV treatment.