title: The therapeutic potential of new investigational hepatitis C virus translation inhibitors.
abstract: BACKGROUND
  Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis, hepatocellular carcinoma and liver-related death worldwide. Currently, the anti-HCV armamentarium encompasses several direct-acting antivirals (DAA) that achieve very high response rates and have an excellent tolerability profile. However, they do not represent a final solution for HCV global eradication for at least these two reasons: i) some patients harbour resistant strains to DAAs and cannot benefit from currently available treatments; ii) the cost of these drugs remains very high.
  
  
  METHODS
  This review summarizes pre-clinical and clinical data regarding HCV translation inhibitors, a new class of drugs currently in the pipeline with novel mechanisms of action.
  
  
  CONCLUSIONS
  The availability of DAAs resolved most issues related to HCV treatment compared with the previous interferon-based therapies. However, there are some patients that cannot achieve a viral clearance with currently available treatments. Therefore, there is still room for new drugs in this setting, providing that they demonstrate an advantage in terms of efficacy, safety, cost or or simplicity of use. Based on preliminary results, at least for some promising molecules (e.g. miravirsen and RG-101), studies on safety and efficacy on this intriguing class of drugs are needed.
authors.affiliation: a Department of Clinical Medicine and Surgery , University of Naples 'Federico II,' Naples , Italy.
authors.forename: Guglielmo
authors.initials: G
authors.lastname: Borgia
authors.affiliation: a Department of Clinical Medicine and Surgery , University of Naples 'Federico II,' Naples , Italy.
authors.forename: Alberto Enrico
authors.initials: AE
authors.lastname: Maraolo
authors.affiliation: a Department of Clinical Medicine and Surgery , University of Naples 'Federico II,' Naples , Italy.
authors.forename: Antonio Riccardo
authors.initials: AR
authors.lastname: Buonomo
authors.affiliation: a Department of Clinical Medicine and Surgery , University of Naples 'Federico II,' Naples , Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Scotto
authors.affiliation: a Department of Clinical Medicine and Surgery , University of Naples 'Federico II,' Naples , Italy.
authors.forename: Ivan
authors.initials: I
authors.lastname: Gentile
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016527:Drug Costs; D024882:Drug Resistance, Viral; D015507:Drugs, Investigational / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016174:Hepacivirus / Q000187:drug effects; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans
chemical_list: D000998:Antiviral Agents; D015507:Drugs, Investigational
keywords: AVI-4065; DAA; HCV; ISIS-14803; Miravirsen; RG-101; SPC3649; TT-034; life cycle; translation inhibitors