NS3 helicase inhibitory potential of the marine sponge Spongia irregularis

Enas Reda Abdelaleem; Mamdouh Nabil Samy; Taha F S Ali; Muhamad Mustafa; Mahmoud A A Ibrahim; Gerhard Bringmann; Safwat A Ahmed; Usama Ramadan Abdelmohsen; Samar Yehia Desoukey

doi:10.1039/d1ra08321j

NS3 helicase inhibitory potential of the marine sponge Spongia irregularis

RSC Adv. 2022 Jan 21;12(5):2992-3002. doi: 10.1039/d1ra08321j. eCollection 2022 Jan 18.

Authors

Enas Reda Abdelaleem¹, Mamdouh Nabil Samy¹, Taha F S Ali², Muhamad Mustafa³, Mahmoud A A Ibrahim⁴, Gerhard Bringmann⁵, Safwat A Ahmed⁶, Usama Ramadan Abdelmohsen^{1

7}, Samar Yehia Desoukey¹

Affiliations

¹ Department of Pharmacognosy, Faculty of Pharmacy, Minia University 61519 Minia Egypt usama.ramadan@mu.edu.eg.
² Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University 61519 Minia Egypt.
³ Medicinal Chemistry Department, Faculty of Pharmacy, Deraya University New Minia 61111 Egypt.
⁴ Computational Chemistry Laboratory, Chemistry Department, Faculty of Science, Minia University 61519 Minia Egypt.
⁵ Institute of Organic Chemistry, University of Würzburg Am Hubland 97074 Würzburg Germany.
⁶ Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University Ismailia 41522 Egypt.
⁷ Department of Pharmacognosy, Faculty of Pharmacy, Deraya University New Minia 61111 Egypt.

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.