title: Direct-acting and host-targeting HCV inhibitors: current and future directions.
abstract: The inclusion of NS3 protease inhibitors to the interferon-containing standard of care improved sustained viral response rates in hepatitis C virus (HCV) infected patients. However, there is still an unmet medical need as this drug regimen is poorly tolerated and lacks efficacy, especially in difficult-to-treat patients. Intense drug discovery and development efforts have focused on direct-acting antivirals (DAA) that target NS3 protease, NS5B polymerase and the NS5A protein. DAA combinations are currently assessed in clinical trials. Alternative antivirals have emerged that target host machineries co-opted by HCV. Finally, continuous and better understanding of HCV biology allows speculating on the value of novel classes of DAA required in future personalized all-oral interferon-free combination therapy and for supporting global disease eradication.
authors.affiliation: Institut de Recherche en Immunologie et en Cancérologie (IRIC), Montréal, Québec H3T 1J4, Canada.
authors.forename: Laurent
authors.initials: L
authors.lastname: Chatel-Chaix
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Germain
authors.forename: Matthias
authors.initials: M
authors.lastname: Götte
authors.forename: Daniel
authors.initials: D
authors.lastname: Lamarre
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D055808:Drug Discovery / Q000639:trends; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases