Hepatitis C is still a serious liver case of health. Up to now the development of anti-Hepatitis C Virus (HCV) drugs is challenging, especially the development of natural material compounds as anti-HCV. In the present study, we evaluated the probability of α-mangostin, piperine, and β-sitosterol as anti-HCV with the in silico and in vitro approaches. Molecular docking was performed between nonstructural protein 5B (NS5B, PDB ID 3FQL) with α-mangostin, piperine, and β-sitosterol by Autodock Tools® and BIOVIA Discovery Studio®. Subsequently, molecular dynamics simulations were conducted for 200 ns, evaluating the dynamic interaction between the ligands and the viral protein NS5B. Furthermore, compound characterization at the hepatocarcinoma cell line was employed. α-Mangostin with NS5B complex demonstrated the most negative binding free energy value based on MM-PBSA calculation with a value of −9.13 kcal/mol. In vitro test showed that IC50 of α -mangostin was 2.70 ± 0.92 μM, IC50 of piperine was 52.18 ± 3.21 μM, IC50 of β-sitosterol was >100 μM. α-Mangostin can serve as a valuable lead compound for further development of the anti-HCV.
- Anti-Hepatitis C