title: [Inhibitors of hepatitis C virus--therapeutic possibilities].
abstract: The search for new drugs against HCV contains new ways to obtain pro-drugs which inhibit translation and block viral proteins, and inhibit host proteins important in HCV-induced pathogenesis. This group of agents are serine protease NS3 inhibitors (telaprevir, boceprevir, R-7227, TMC-435, SCH 900518, GS-9256). The most advanced studies are developed with telaprevir and boceprevir; at present their effect in combined therapy with PegIFN-alpha and RBV in the III clinical phase is tested. The sustained viral response (SVR) was achieved at the level of 60-75%. This group of agents contains also inhibitors of NS5A domain, e.g. PPI-461 which shows antiviral and cytotoxic activity. The following prodrugs are NS3 helicase inhibitors, e.g. p14 peptide, whose IC50 equals 725 nM. Studies are continued on viral entry inhibitors (ITX-5061), therapeutic vaccines (IC-41, civaci, TG-4040, CT-1011, GI-5005) and immunomodulating preparations (ANA-773, IMO-3649, NOV-205). The agents acting on host proteins are a.o. cyclophilin inhibitors. The most advanced studies concern DEBIO 025 preparation which after phase I and II, underwent phase III of clinical studies in February 2010. Since 5 years there is a possibility to investigate the effects of these comounds in vitro with the use of Huh-7 line infected with HCV. These investigations allow to estimate the antiviral effectiveness and cytotoxicity of agents, and resistance of viral strains.
authors.affiliation: Pracownia Immunopatologii Zakazeń Wirusami Hepatotropowymi Zakładu Wirusologii, Narodoweg Instytutu Zdrowia Publicznego-Państwowego Zakładu Higieny, Warszawa.
authors.forename: Paulina
authors.initials: P
authors.lastname: Godzik
authors.forename: Marcin
authors.initials: M
authors.lastname: Komorowski
authors.forename: Joanna
authors.initials: J
authors.lastname: Cielecka-Kuszyk
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Madaliński
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D015507:Drugs, Investigational / Q000494:pharmacology*; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D011355:Prodrugs / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000494:pharmacology*; D017361:Viral Nonstructural Proteins / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D015507:Drugs, Investigational; D011355:Prodrugs; D012697:Serine Endopeptidases; D017361:Viral Nonstructural Proteins; C080102:NS2B protein, flavivirus; C504449:NS3 protease, dengue virus; D000085242:Viral Proteases