Anti-HCV protease of diketopiperazines produced by the Red Sea sponge-associated fungus Aspergillus versicolor


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Abstract

Hepatitis C virus (HCV) infection is a global problem due to the difficulties in developing a protective vaccine. In this work, we demonstrated that the ethyl acetate extract of the endophytic fungus Aspergillus versicolor exhibited significant activity against HCV NS3/4A protease with IC50 value of 30 μg/mL. The fungus was isolated from the Red Sea black sponge Spongia officinalis and identified by its morphology and 18S rDNA. Large-scale fermentation of the fungus followed by chromatographic purification with silica gel, Sephadex LH-20 and semipreparative HPLC of the active extract led to isolation of some known metabolites related to cyclodipeptides and the so-called diketopiperazines (DKPs). The DKP, cyclo(L-Tyr-L-Pro), displayed strong effect as HCV protease inhibitor with IC50 value of 8.2 μg/mL. A computational docking study of cyclo(L-Tyr-L-Pro) against HCV protease was used to formulate a hypothetical mechanism for the inhibitory activity of the active compound on the tested enzyme.

About the authors

E. F. Ahmed

Natural and Microbial Products Chemistry Department

Email: uhawas@kau.edu.sa
Egypt, Dokki, Cairo

M. E. Rateb

Department of Pharmacognosy, College of Pharmacy; School of Science & Sport

Email: uhawas@kau.edu.sa
Egypt, Beni-Suief; Paisley

L. T. Abou El-Kassem

Pharmacognosy Department

Email: uhawas@kau.edu.sa
Egypt, Dokki, Cairo

Usama W. Hawas

Marine Chemistry Department, Faculty of Marine Sciences

Author for correspondence.
Email: uhawas@kau.edu.sa
Saudi Arabia, Jeddah, 21589

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