Anti-HCV protease potential of endophytic fungi and cytotoxic activity

Forty-eight endophytic fungal strains were isolated and purified from ten Egyptian medicinal plants and their culture broth extracts were explored for HCV protease inhibitory activity and cytotoxicity. The ethyl acetate extracts of Alternaria alternata PGL-3, Cochlibolus lunatus PML-17, Nigrospora sphaerica EPS-38, followed by Emerecilla nidulans RPL-21 showed the most potent inhibition of HCV NS3/4A protease with IC50 17.0, 20.5, 33.6, and 54.6 mu g/ml, respectively, with low cytotoxicity except for the later. The extracts of Emericella nidulans RSL-24, Fusarium oxysporum SML-41, Emericella nidulans RPL-21, and Penicillium sp. RSL-43 exhibited strong cytotoxic activity against human breast cancer cell lines (MCF-7) with IC50 10.8, 11.0, 12.5, and 13.7 mu g/ml, respectively. Emericella nidulans RSS-22, Emericella nidulans RSL-24, and Fusarium oxysporum SML-41 displayed a potent cytotoxic effect on human liver cancer cell lines (HEP-G2) with IC50 14.8, 20.3 and 24.0 mu g/ml, respectively. Alternariol and alternariol -9-methyl ether were isolated from the ethyl acetate extract of Alternaria alternata PGL-3 whereas, emericellin, shamixanthone, arugosin C were isolated from the ethyl acetate extract of Emericella nidulans RPL-21. The results suggest Alternaria alternata PGL-3 endophyte from Punica granatum peel as a source of antiviral lead.