title: Direct-acting antiviral agents for hepatitis C: structural and mechanistic insights.
abstract: The treatment of HCV infection has evolved at an extremely rapid pace over the past few years. The development of direct-acting antiviral agents, which potently inhibit different stages in the viral life cycle, has led to the replacement of interferon with well-tolerated oral therapies with cure rates of >90% in most patient populations. Understanding the mechanisms of action of the various agents as well as related issues, including the molecular basis for resistance, helps to guide drug development and clinical use. In this Review, we provide a mechanistic description of NS3/4A protease inhibitors, nucleotide and non-nucleotide inhibitors of the NS5B viral polymerase and inhibitors of the NS5A protein, followed by a summary of clinical data from studies of each drug class alone and in combination. Remaining challenges in drug development efforts are also discussed.
authors.affiliation: Department of Medical Microbiology &Immunology, 6-020K Katz Group Centre, University of Alberta, Edmonton, Alberta, T6G 2E1, Canada.
authors.forename: Matthias
authors.initials: M
authors.lastname: Götte
authors.affiliation: Toronto Centre for Liver Disease, University Health Network, University of Toronto, 200 Elizabeth Street, Toronto, Ontario, M5C 2C4, Canada.
authors.forename: Jordan J
authors.initials: JJ
authors.lastname: Feld
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D009711:Nucleotides / Q000037:antagonists & inhibitors; D011480:Protease Inhibitors / Q000627:therapeutic use*; D012254:Ribavirin / Q000627:therapeutic use; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D009711:Nucleotides; D011480:Protease Inhibitors; D012254:Ribavirin; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase