title: Hepatitis C therapy with HCV NS5B polymerase inhibitors.
abstract: BACKGROUND
  Several HCV polymerase inhibitors are in advanced stages of clinical development. They are nucleos(t)ide and non-nucleoside analogs. Nucleos(t)ides inhibit viral replication acting as chain terminators whereas non-nucleosides block allosterically the HCV polymerase. Sofosbuvir is an uridine analog and currently the most promising HCV polymerase inhibitor, being active across all HCV genotypes. It has good tolerability and a robust barrier to resistance. In contrast, non-nucleoside analogs have low to moderate antiviral potency, a low barrier to resistance and inhibit only HCV genotype 1.
  
  
  METHODS
  Studies conducted with distinct HCV polymerase inhibitors as part of interferon-free combinations have opened a new landscape in which shorter treatment duration and all-oral regimens are envisioned as the future curative treatment for most chronic hepatitis C patients.
  
  
  CONCLUSIONS
  Antiviral drug development for HCV is progressing at a feverish pace. Amongst HCV polymerase inhibitors, sofosbuvir has positioned as unique companion with ribavirin as therapy for most HCV genotypes 2 or 3, and along with NS5A inhibitors for other HCV genotypes. Non-nucleoside HCV polymerase inhibitors are being developed only as part of all-oral combinations with protease inhibitors. The expected high cost of DAAs will preclude their prompt and wider use, allowing room for using alternative cheaper options in easier-to-treat patient populations.
authors.affiliation: Hospital Carlos III, Department of Infectious Diseases, Calle Sinesio Delgado 10, Madrid 28029, Spain. vsoriano@dragonet.es
authors.forename: Vincent
authors.initials: V
authors.lastname: Soriano
authors.forename: Eugenia
authors.initials: E
authors.lastname: Vispo
authors.forename: Carmen
authors.initials: C
authors.lastname: de Mendoza
authors.forename: Pablo
authors.initials: P
authors.lastname: Labarga
authors.forename: Jose Vicente
authors.initials: JV
authors.lastname: Fernandez-Montero
authors.forename: Eva
authors.initials: E
authors.lastname: Poveda
authors.forename: Ana
authors.initials: A
authors.lastname: Treviño
authors.forename: Pablo
authors.initials: P
authors.lastname: Barreiro
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D009705:Nucleosides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D009711:Nucleotides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D009705:Nucleosides; D009711:Nucleotides; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase