Background: Marine algal-derived endophytic fungi have attracted considerable attention in
the recent decade due to their prolific production of structurally diverse secondary metabolites with
various biological activities. In this study, the potential inhibition of endophytic fungi isolated from
Red Sea brown alga Sargassum subrepandum was examined against HCV protease enzyme.
Methods: An in vitro HCV NS3-4A protease assay was used to evaluate the HCV protease inhibition
activity of the fungi. The fungus with a high-level inhibition was identified based on 18S rDNA and
further subjected to chemical and biological investigations on its secondary metabolites.
Results: The endophytic fungal strains, Aspergillus parasiticus, Aspergillus terreus and Geotrichum
candidum were isolated from Red Sea brown alga Sargassum subrepandum. Of the three fungi, Aspergillus
terreus had the highest HCV protease inhibition activity (IC50 10 μg/mL). From that fungus,
eleven compounds were isolated and their structures were elucidated on the basis of NMR and MS
spectroscopic analysis. Moreover, sophisticated 2-dimensional NMR spectroscopy of the isolated
symmetric diketopiperazine bisdethiodi(methylthio)acetylaranotin has been recorded. Of the compounds
in the A. terreus extract, only bisdethiodi(methylthio)acetylaranotin and cyclo(L-Tyr-L-Pro)
were shown to have a potent HCV PR inhibition with IC50 13.0 and 18.2 μM, respectively.
Conclusion: The present study shows that the organic extract of A. terreus has a potential HCV protease
inhibition activity. These preliminary results are of great interest and can be proposed for new candidate
of anti-HCV agents.