Different Culture Metabolites of the Red Sea Fungus Fusarium equiseti Optimize the Inhibition of Hepatitis C Virus NS3/4A Protease (HCV PR)

• Published in: Marine drugs 2016-10, Vol.14 (10), p.190-190
• Main Authors: Hawas, Usama W, Al-Farawati, Radwan, Abou El-Kassem, Lamia T, Turki, Adnan J
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - pharmacology; Antifungal Agents - pharmacology; Antiviral Agents - pharmacology; brown alga; Culture Media; Fusarium - chemistry; Fusarium equiseti; HCV protease; Hepatitis C virus; Humans; Indian Ocean; Inhibitory Concentration 50; Marine; Microbial Sensitivity Tests; Molecular Docking Simulation; Padina pavonica; Phaeophyceae - microbiology; Protease Inhibitors - pharmacology; Red Sea; Trypsin Inhibitors - pharmacology; Viral Nonstructural Proteins - antagonists & inhibitors
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md14100190

The endophytic fungus was isolated from the brown alga , 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 (IC from 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 IC 10 to 37 μM. The Cz culture extract exhibited high-level inhibition of HCV protease (IC 27.6 μg/mL) compared to the biomalt culture extract (IC 56 μg/mL), and the most potent HCV PR isolated compound (Griseoxanthone C, IC 19.8 μM) from the bio-malt culture extract showed less of an inhibitory effect compared to isolated ω-hydroxyemodin (IC 10.7 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 IC 48.5 and 51.3 μM, respectively.