title: Different Culture Metabolites of the Red Sea Fungus Fusarium equiseti Optimize the Inhibition of Hepatitis C Virus NS3/4A Protease (HCV PR).
abstract: The endophytic fungusFusarium equisetiwas isolated from the brown algaPadina pavonica, collected from the Red Sea. The fungus was identified by its morphology and 18S rDNA. Cultivation of this fungal strain in biomalt-peptone medium led to isolation of 12 known metabolites of diketopeprazines and anthraquinones. The organic extract and isolated compounds were screened for their inhibition of hepatitis C virus NS3/4A protease (HCV PR). As a result, the fungal metabolites showed inhibition of HCV protease (IC50from 19 to 77 μM), and the fungus was subjected to culture on Czapek's (Cz) media, with a yield of nine metabolites with potent HCV protease inhibition ranging from IC5010 to 37 μM. The Cz culture extract exhibited high-level inhibition of HCV protease (IC5027.6 μg/mL) compared to the biomalt culture extract (IC5056 μg/mL), and the most potent HCV PR isolated compound (Griseoxanthone C, IC5019.8 μM) from the bio-malt culture extract showed less of an inhibitory effect compared to isolated ω-hydroxyemodin (IC5010.7 μM) from the optimized Cz culture extract. Both HCV PR active inhibitors ω-hydroxyemodin and griseoxanthone C were considered as the lowest selective safe constituents against Trypsin inhibitory effect with IC5048.5 and 51.3 μM, respectively.
authors: Marine Chemistry Department, Faculty of Marine sciences, King Abdulaziz University, P.O. Box 80207, Jeddah 21589, Saudi Arabia. uhawas@kau.edu.sa.
authors: Usama W
authors: UW
authors: Hawas
authors: Marine Chemistry Department, Faculty of Marine sciences, King Abdulaziz University, P.O. Box 80207, Jeddah 21589, Saudi Arabia. rfarawati@kau.edu.sa.
authors: Radwan
authors: R
authors: Al-Farawati
authors: Pharmacognosy Department, National Research Centre, Dokki 12622, Cairo, Egypt. lamiaetaha@yahoo.com.
authors: Lamia T
authors: LT
authors: Abou El-Kassem
authors: Marine Chemistry Department, Faculty of Marine sciences, King Abdulaziz University, P.O. Box 80207, Jeddah 21589, Saudi Arabia. aturki@kau.edu.sa.
authors: Adnan J
authors: AJ
authors: Turki
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D003470:Culture Media; D005670:Fusarium / Q000737:chemistry*; D006801:Humans; D019156:Indian Ocean; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D000459:Phaeophyceae / Q000382:microbiology; D011480:Protease Inhibitors / Q000494:pharmacology*; D014361:Trypsin Inhibitors / Q000494:pharmacology; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D000998:Antiviral Agents; D003470:Culture Media; D011480:Protease Inhibitors; D014361:Trypsin Inhibitors; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
keywords: Fusarium equiseti; HCV protease; Padina pavonica; Red Sea; brown alga