NS3 helicase inhibitory potential of the marine sponge Spongia irregularis .

In the current study, an investigation of the activity of the total extract of the marine sponge Spongia irregularis and its different fractions against the hepatitis C virus (HCV) was pursued. The results revealed that the ethyl acetate fraction exhibited the highest anti-HCV activity, with an IC 50 value of 12.6 ± 0.05 μg ml -1 . Chromatographic resolution of the ethyl acetate fraction resulted in the isolation of four known compounds, 1,3,7-trimethylguanine (1), 3,5-dihydroxyfuran-2(5 H )-one (2), thymidine (3), and 1H-indazole (4). By using LC-HR-ESI-MS metabolic profiling, compounds 5-14 were also identified in the same fraction. Molecular docking calculations revealed the high binding affinity of compound 14 against the allosteric pocket of HCV NS3-NS4A and the active site of HCV NS3 helicase (-10.1 and -7.4 kcal mol -1 , respectively). Molecular dynamics simulations, followed by molecular mechanics-generalized Born surface area energy calculations, demonstrated the structural and energetic stability of compound 14 in complex with HCV targets.