NS3 helicase inhibitory potential of the marine sponge Spongia irregularis
Abdelaleem, E.R.; Samy, M.N.; Ali, T.F.S.; Mustafa, M.; Ibrahim, M.A.A.; Bringmann, G.; Ahmed, S.A.; Abdelmohsen, U.R.; Desoukey, S.Y. (2022). NS3 helicase inhibitory potential of the marine sponge Spongia irregularis. Rsc Advances 12(5): 2992-3002. https://dx.doi.org/10.1039/d1ra08321j
In: RSC Advances. Royal Society of Chemistry: Cambridge. e-ISSN 2046-2069, meer
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| Auteurs | | Top |
- Abdelaleem, E.R.
- Samy, M.N.
- Ali, T.F.S.
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- Mustafa, M.
- Ibrahim, M.A.A.
- Bringmann, G.
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- Ahmed, S.A.
- Abdelmohsen, U.R.
- Desoukey, S.Y.
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| Abstract |
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 IC50 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(5H)-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. |
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