title: Ribavirin for the treatment of chronic hepatitis C virus infection: a review of the proposed mechanisms of action.
abstract: Roughly 20 years after the discovery of the hepatitis C virus (HCV), and 10 years after the launch of the current standard of care (SOC) therapy, i.e. the combination of pegylated interferon-alpha and ribavirin, antiviral treatment of chronic hepatitis C is at the dawn of a new era. The current SOC will be combined with a direct acting antiviral (DAA), i.e. either the HCV NS3 protease inhibitor Telaprevir or Boceprevir. Combinations of DAAs may have the potential to completely cure chronic HCV infection. Clinical data suggest that ribavirin may remain at least for some time, an important component even in combinations of different DAAs. Ironically, and much in contrast to the DAAs, the precise mechanism(s) by which ribavirin exerts its anti-HCV activity in infected patients still waits to be unravelled. Here we review the current views on the mechanism of action of ribavirin against chronic infections with HCV. Concerted efforts of modern pharmacogenetics, novel insights into innate immunity and contributions from molecular virology will hopefully allow deciphering the precise mechanism(s) that are at the basis of the antiviral effect of this nucleoside analogue. Such insights may help design improved strategies to fight chronic infections with HCV.
authors.affiliation: Rega Institute for Medical Research, Minderbroedersstraat 10, KU Leuven, B-3000 Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Paeshuyse
authors.forename: Kai
authors.initials: K
authors.lastname: Dallmeier
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004359:Drug Therapy, Combination / Q000379:methods; D016174:Hepacivirus / Q000302:isolation & purification*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D009842:Oligopeptides / Q000627:therapeutic use; D010597:Pharmacogenetics; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D009842:Oligopeptides; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C417083:peginterferon alfa-2b