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

The endophytic fungus Fusarium equiseti was isolated from the brown alga Padina 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 (IC₅₀ 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 IC₅₀ 10 to 37 μM. The Cz culture extract exhibited high-level inhibition of HCV protease (IC₅₀ 27.6 μg/mL) compared to the biomalt culture extract (IC₅₀ 56 μg/mL), and the most potent HCV PR isolated compound (Griseoxanthone C, IC₅₀ 19.8 μM) from the bio-malt culture extract showed less of an inhibitory effect compared to isolated ω-hydroxyemodin (IC₅₀ 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 IC₅₀ 48.5 and 51.3 μM, respectively.