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Hepatitis C Virus NS3 Protease and Helicase Inhibitors from Red Sea Sponge (Amphimedon) Species in Green Synthesized Silver Nanoparticles Assisted by in Silico Modeling and Metabolic Profiling

Authors Shady NH, Khattab AR, Ahmed S, Liu M, Quinn RJ, Fouad MA, Kamel MS, Muhsinah AB, Krischke M, Mueller MJ, Abdelmohsen UR

Received 7 October 2019

Accepted for publication 29 January 2020

Published 12 May 2020 Volume 2020:15 Pages 3377—3389


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Anderson Oliveira Lobo

Nourhan Hisham Shady,1 Amira R Khattab,2 Safwat Ahmed,3 Miaomiao Liu,4 Ronald J Quinn,4 Mostafa A Fouad,5 Mohamed Salah Kamel,5 Abdullatif Bin Muhsinah,6 Markus Krischke,7 Martin J Mueller,7 Usama Ramadan Abdelmohsen1,5

1Department of Pharmacognosy, Faculty of Pharmacy, Deraya University, Universities Zone, Minia 61111, Egypt; 2Department of Pharmacognosy, College of Pharmacy, Arab Academy for Science, Technology and Maritime Transport, Alexandria 1029, Egypt; 3Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt 41522; 4Griffith Institute for Drug Discovery, Griffith University, Brisbane, Queensland 4111, Australia; 5Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia 61519, Egypt; 6Department of Pharmacognosy, College of Pharmacy, King Khalid University, Abha 61441, Saudi Arabia; 7Department of Pharmaceutical Biology, Julius-von-Sachs Institute for Biological Sciences, University of Würzburg, Würzburg 97082, Germany

Correspondence: Martin J Mueller; Usama Ramadan Abdelmohsen Tel +49 9313186160
; +20 86-2347759
Fax +49 9313186182
; +20 86-2369075

Background: Hepatitis C virus (HCV) infection is a major cause of hepatic diseases all over the world. This necessitates the need to discover novel anti-HCV drugs to overcome emerging drug resistance and liver complications.
Purpose: Total extract and petroleum ether fraction of the marine sponge (Amphimedon spp.) were used for silver nanoparticle (SNP) synthesis to explore their HCV NS3 helicase- and protease-inhibitory potential.
Methods: Characterization of the prepared SNPs was carried out with ultraviolet-visible spectroscopy, transmission electron microscopy, and Fourier-transform infrared spectroscopy. The metabolomic profile of different Amphimedon fractions was assessed using liquid chromatography coupled with high-resolution mass spectrometry. Fourteen known compounds were isolated and their HCV helicase and protease activities assessed using in silico modeling of their interaction with both HCV protease and helicase enzymes to reveal their anti-HCV mechanism of action. In vitro anti-HCV activity against HCV NS3 helicase and protease was then conducted to validate the computation results and compared to that of the SNPs.
Results: Transmission electron–microscopy analysis of NPs prepared from Amphimedon total extract and petroleum ether revealed particle sizes of 8.22– 14.30 nm and 8.22– 9.97 nm, and absorption bands at λmax of 450 and 415 nm, respectively. Metabolomic profiling revealed the richness of Amphimedon spp. with different phytochemical classes. Bioassay-guided isolation resulted in the isolation of 14 known compounds with anti-HCV activity, initially revealed by docking studies. In vitro anti–HCV NS3 helicase and protease assays of both isolated compounds and NPs further confirmed the computational results.
Conclusion: Our findings indicate that Amphimedon, total extract, petroleum ether fraction, and derived NPs are promising biosources for providing anti-HCV drug candidates, with nakinadine B and 3,4-dihydro-6-hydroxymanzamine A the most potent anti-HCV agents, possessing good oral bioavailability and penetration power.

Keywords: Amphimedon, nanoparticles, marine sponge, natural products, HCV helicase, protease, molecular docking, metabolomics

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