title: Nucleoside/nucleotide analogue polymerase inhibitors in development.
abstract: Nucleoside/nucleotide analogue polymerase inhibitors (NPIs) are analogues of natural substrates that bind the active site of NS5B and terminate viral RNA chain generation and generally provide a high genetic barrier to resistance and are effective in all genotypes. NPIs such as sofosbuvir (GS-7977) show high antiviral activities that, together with their high genetic barrier to resistance, suggest that they are optimal backbone candidates for all-oral combination therapies. Several trials are ongoing to further define the potential of all-oral regimens with sofosbuvir (GS-7977). Recent interim analyses indicate that many patients treated with only 2 direct-acting antiviral agents experience viral breakthrough, which can be significantly reduced by the addition of ribavirin without pegylated interferon α.
authors.affiliation: Division of Gastroenterology/Hepatology, Liver Disease Center, Scripps Clinic, La Jolla, CA 92067, USA. pockros.paul@scrippshealth.org
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Pockros
mesh_terms: D003562:Cytidine / Q000031:analogs & derivatives; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D015507:Drugs, Investigational / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D016174:Hepacivirus / Q000201:enzymology*; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D011487:Protein Conformation; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors*; D000069474:Sofosbuvir; D014542:Uridine Monophosphate / Q000031:analogs & derivatives / Q000627:therapeutic use; D017361:Viral Nonstructural Proteins
chemical_list: C552098:2'-fluoro-2'-methyl-3',5'-diisobutyryldeoxycytidine; D015507:Drugs, Investigational; D004791:Enzyme Inhibitors; D017361:Viral Nonstructural Proteins; D003841:Deoxycytidine; D003562:Cytidine; D014542:Uridine Monophosphate; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; D000069474:Sofosbuvir