Hepatitis C virus NS3-NS4A protease inhibitors from the endophytic Penicillium chrysogenum isolated from the red alga Liagora viscida.
Hepatitis C virus (HCV) NS3-NS4A protease is an attractive target for anti-HCV agents because of its important role in replication. In this work, we demonstrated that the ethyl acetate extract of the endophytic fungus Penicillium chrysogenum exhibited a potent activity against HCV NS3-NS4A protease with an IC50 value of 20 microg/ml. The fungus was isolated from the red alga Liagora viscida and identified by its morphology and 18S rDNA. Large-scale fermentation of the fungus in Czapek's peptone liquid medium followed by chromatographic purification of the active extract from the liquid medium allowed the isolation of twelve known metabolites. The biological properties of the isolated compounds were explored for anti-HCV protease as well as antimicrobial and anticancer activities. A computational docking study of the active isolated compounds against HCV protease was used to formulate a hypothetical mechanism for the inhibitory activity of the active compounds on the tested enzymes.
Marine Chemistry Department, Faculty of Marine Sciences, King Abdulaziz University, P. O. Box 80207, Jeddah 21589, Kingdom of Saudi Arabia. hawasusama@yahoo.com
Usama W
UW
Hawas
Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini St. 11562, Cairo, Egypt.
Ali M
AM
El-Halawany
Chemistry of Natural and Microbial Products Department, National Research Centre, 12311-Dokki, Cairo, Egypt.
Eman F
EF
Ahmed
D003470:Culture Media; D004354:Drug Screening Assays, Antitumor; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D010408:Penicillium chrysogenum / Q000201:enzymology* / Q000302:isolation & purification; D011480:Protease Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology; D000461:Rhodophyta / Q000382:microbiology*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D003470:Culture Media; D011480:Protease Inhibitors; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C093542:NS4 protein, hepatitis C virus