Abstract
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.
Highlights
Hepatitis C virus (HCV) infection is a global public health problem with an estimated approximately 200 million people worldwide at risk of developing life-threatening liver diseases, leading to liver fibrosis, liver cirrhosis, hepatocellular carcinoma, and death [1]
Results and Discussion analyses and comparison with the literature data. These compounds were evaluated for their inhibitory effect on HCV NS3/4A protease using a SensoLyteTM 520 HCV protease assay kit, as well
The identification the isolated fungus Fusarium equiseti from Red Sea alga Padina pavonica
Summary
Hepatitis C virus (HCV) infection is a global public health problem with an estimated approximately 200 million people worldwide at risk of developing life-threatening liver diseases, leading to liver fibrosis, liver cirrhosis, hepatocellular carcinoma, and death [1]. Based on the screening model of HCV protease inhibitors, different culture extracts of the Red macrocyclic lactone with high binding affinity to oestrogen‐responsive proliferation of MCF‐7 cells sea fungus Fusarium equiseti found to bebecomes active and 21 secondary metabolites were isolated and and only low acute were toxicity [13]. Observed in metabolite amounts andalso composition among analyses and comparison withdiversity the literature These compounds were evaluated for their natural F. equiseti populations, where, FUSCHR and ZEA are the most commonly occurring [9]. Fusarium equiseti were found to be active and 21 secondary metabolites were isolated and identified from both culture extracts. The culture broth extract was evaluated for its inhibition the fungal metabolites showed potent activity, and the fungus wasinvestigation subjected of foritsfurther different of HCV NS3/4A protease and submitted for further chemical secondary culture optimization. These compounds were isolated for the first time from Red Sea fungus F. equiseti
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