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

Abstract

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 helicaseand 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-HCVactivity 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 λ max of 450 and 415 nm, respectively. Metabolomic profiling revealed the richness of Amphimedon spp. with different phytochemical classes. Bioassayguided 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.

Targeting 3CLpro and SARS-CoV-2 RdRp by Amphimedon sp. Metabolites: A Computational Study

“…The petroleum ether fraction was first chromatographed on a silica-gel column, and was then subjected to a sephadex LH-20 column and final purification on semi-preparative HPLC, yielding compounds 1 – 14 . These 14 compounds, as shown in Figure 1 , were identified based on their HR-ESIMS and by comparison with the literature, as nakinadine B ( 1 ), ircinol A ( 2 ), 6-hydroxymanzamine A ( 3 ), 3,4-dihydromanzamine A, J N-oxide ( 4 ), manzamine D ( 5 ), 3,4-dihydro-6-hydroxymanzamine A ( 6 ), pyrinodemin D ( 7 ), 7-methyl-6-hexadecenoic acid ( 8 ), methyl 2-methoxyhexadecanoate ( 9 ), 11,15-icosadienoicacid ( 10 ), 20-hepacosenoic acid ( 11 ), amphimedoside C ( 12 ), keramaphidin B ( 13 ), and amphimedine ( 14 ) [ 16 ].…”

“…We previously studied the antiviral potential of Amphimedon sp., and our results indicated that Amphimedon sp. total extract and petroleum ether fractions, as well as their derived nanoparticles, had anti-HCV potential, with pyrinodemin D, nakinadine B, and 3,4-dihydro-6-hydroxymanzamine A being the most potent anti-HCV agents [ 16 ]. This prompted us to study the ability of isolated compounds to act as inhibitors of COVID-19.…”

In silico Study of Potential anti-SARS Cell Entry Phytoligands From Phlomis aurea : A Promising Avenue for Prophylaxis

“…Recently, in silico prediction studies of physicochemical properties, ADMET and drug-likeness parameters are utilized for the identification of the most promising leads. Herein, SwissADME software was employed to compute the physicochemical properties formulating drug-likeness parameters of the hit phytochemicals ( Table 2 ) [ 18 , 28 ].…”

Synthesis approach-dependent antiviral properties of silver nanoparticles and nanocomposites

“…In addition, the silver nanoparticle directly binds with the viral genome, disrupts their structure, and halts their proliferation in the host body [ 217 ]. Notably, the biogenic synthesized silver nanoparticle follows the same mechanism when a virus infects a host cell [ 218 ]. However, the chemical-based functional group in the AgNPs fabricated via physical or chemical approach can be toxic towards the infected host cell [ 219 ].…”