title: NS5A inhibitors in the treatment of hepatitis C.
abstract: Hepatitis C virus infection is a major health problem worldwide and no vaccine has yet been developed against this virus. In addition, currently approved pharmacotherapies achieve suboptimal cure rates and have side effects that result in non-compliance and premature treatment discontinuation. Significant research has been devoted to developing direct-acting antiviral agents that inhibit key viral functions. In particular, several novel drug candidates that inhibit the viral non-structural protein 5A (NS5A) have been demonstrated to possess high potency, pan-genotypic activity, and a high barrier to resistance. Clinical trials using combination therapies containing NS5A inhibitors have reported results that promise high cure rates and raise the possibility of developing interferon-free, all-oral regimens.
authors.affiliation: National Reference Centre for Viral Hepatitis B, C and Delta, Department of Virology, Henri Mondor Hospital, University of Paris-Est, Créteil, France; INSERM U955, Créteil, France. jean-michel.pawlotsky@hmn.aphp.fr
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Pawlotsky
mesh_terms: D000284:Administration, Oral; D000813:Anilides / Q000627:therapeutic use; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use; D002219:Carbamates / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005449:Fluorenes / Q000627:therapeutic use; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D011392:Proline; D011759:Pyrrolidines; D014633:Valine / Q000031:analogs & derivatives; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000813:Anilides; D000998:Antiviral Agents; D001562:Benzimidazoles; D002219:Carbamates; D005449:Fluorenes; D007093:Imidazoles; D011392:Proline; D011759:Pyrrolidines; D014633:Valine; D017361:Viral Nonstructural Proteins; C586541:ledipasvir; C586094:ombitasvir; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C549273:daclatasvir
keywords: DAA; Daclatasvir; HCV; Hepatitis C virus; IFN; IRES; NS; NS5A inhibitor; RNA-dependent RNA polymerase; RVR; RdRp; Resistance; SVR; UTR; cEVR; complete early virologic response; direct acting antiviral; hepatitis C virus; interferon; internal ribosome entry site; nonstructural; rapid virologic response; sustained virological response; untranslated region