title: Synergy of a hepatitis C virus (HCV) NS4A antagonist in combination with HCV protease and polymerase inhibitors.
abstract: Rapid emergence of resistance to monotherapy with virus-specific inhibitors necessitates combination therapy. ACH-806 is a hepatitis C virus NS4A inhibitor with a novel mechanism of action and resistance pathway. This compound was synergistic with NS3 protease inhibitors and NS5B nucleoside and nonnucleoside polymerase inhibitors.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of California, 9500 Gilman Drive, MC 0711, La Jolla, CA 92093, USA. dwyles@ucsd.edu
authors.forename: David L
authors.initials: DL
authors.lastname: Wyles
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Kaihara
authors.forename: Robert T
authors.initials: RT
authors.lastname: Schooley
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D024882:Drug Resistance, Viral; D004357:Drug Synergism; D016174:Hepacivirus / Q000187:drug effects*; D006801:Humans; D015394:Molecular Structure; D010670:Phenylthiourea / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*
chemical_list: C530651:1-(4-pentyloxy-3-trifluoromethylphenyl)-3-(pyridine-3-carbonyl)thiourea; D000998:Antiviral Agents; C080106:NS4A protein, flavivirus; D011480:Protease Inhibitors; D017361:Viral Nonstructural Proteins; D010670:Phenylthiourea; D012324:RNA-Dependent RNA Polymerase