title: Progress in the development of anti-hepatitis C virus nucleoside and nucleotide prodrugs.
abstract: The search for new anti-hepatitis C virus (HCV) therapeutics continues as the current treatment, consisting of PEGylated IFN-α and ribavirin, is of limited efficacy, nonspecific and can cause significant side effects. Modified nucleoside analogues with improved efficacy and selectivity, may become the backbone of the future standard of care for anti-HCV therapies. Several families of modified nucleoside are known to inhibit HCV RNA-dependent RNA polymerase, a vital enzyme for viral replication. Ongoing efforts are focused on improvement of potency, selectivity and delivery of antiviral nucleoside analogues, with several recent promising advances into clinical trials. This review summarizes the current progress in the development of new anti-HCV nucleoside and nucleotide prodrugs.
authors.affiliation: Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff, CF10 3NB, UK.
authors.forename: Karolina
authors.initials: K
authors.lastname: Madela
authors.forename: Christopher
authors.initials: C
authors.lastname: McGuigan
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D016174:Hepacivirus / Q000187:drug effects*; D006526:Hepatitis C / Q000188:drug therapy; D006801:Humans; D009705:Nucleosides / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D011355:Prodrugs / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D009705:Nucleosides; D011355:Prodrugs; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase