title: Non-nucleoside inhibitors of hepatitis C virus polymerase: current progress and future challenges.
abstract: The current standard of care for hepatitis C virus (HCV) infection is a combination of PEGylated interferon and ribavirin, which offer limited efficacy and significant side effects. Novel HCV-specific inhibitors, including those directed at the viral polymerase, have become the focus of HCV drug-discovery efforts in the past decade. In addition to the active site targeted by traditional nucleoside inhibitors, at least four different allosteric-binding sites have been reported for the HCV polymerase, which offer ample opportunities for small-molecule inhibitors. In this review, we summarize the recent progress in the discovery of non-nucleoside HCV polymerase inhibitors with a focus on novel chemical matters, their clinical efficacy, safety and potential for combination therapy.
authors.affiliation: Pfizer Global Research and Development, La Jolla Laboratories, 10770 Science Center Drive, San Diego, CA 9212, USA. hui.li@pfizer.com
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Stephanie T
authors.initials: ST
authors.lastname: Shi
mesh_terms: D000495:Allosteric Site; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000627:therapeutic use*; D001665:Binding Sites; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D016174:Hepacivirus / Q000201:enzymology*; D006526:Hepatitis C / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D008099:Liver / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D011487:Protein Conformation; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D017361:Viral Nonstructural Proteins