title: Peptide inhibitors of hepatitis C virus NS3 protease.
abstract: Hepatitis C virus (HCV) is a highly prevalent virus and one of the major agents of chronic hepatitis. Since HCV NS3 protease is essential for the processing of HCV polyprotein, this protease is a target of choice to control HCV replication. Peptide inhibitors of NS3 were developed by selective amino acid replacement of six leader sequences, corresponding to regions of HCV polyprotein that are cleaved by NS3. The large numbers of potential 14-mer and 16-mer peptide inhibitors thus obtained were tested against NS3 using the fluorescent probe RETS1 and peptide cofactor SVVIVGRIILSGRA from NS4A protein. This afforded several peptide inhibitors with an IC50 of around 2 microM. These peptides may be good leading compounds for the development of peptidomimetics to control HCV replication in the treatment of chronic hepatitis C.
authors.affiliation: Department of Genetics, Faculty of Science, University of Navarra, Pamplona, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Portal-Núñez
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: González-Navarro
authors.forename: Marina
authors.initials: M
authors.lastname: García-Delgado
authors.forename: José Luis
authors.initials: JL
authors.lastname: Vizmanos
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Lasarte
authors.forename: Francisco
authors.initials: F
authors.lastname: Borrás-Cuesta
mesh_terms: D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology; D006526:Hepatitis C / Q000188:drug therapy; D006801:Humans; D006868:Hydrolysis; D020128:Inhibitory Concentration 50; D007700:Kinetics; D018716:Molecular Mimicry; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D009842:Oligopeptides; 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