Hepatitis C virus (HCV) NS5B nonnucleoside inhibitors specifically block single-stranded viral RNA synthesis catalyzed by HCV replication complexes in vitro.
Replication complexes of hepatitis C virus synthesized two major species of viral RNA in vitro, double stranded and single stranded. NS5B nonnucleoside inhibitors inhibited dose dependently the synthesis of single-stranded RNA but not double-stranded RNA. Moreover, replication complexes carrying a mutation resistant to a nonnucleoside inhibitor lost their susceptibilities to the inhibitor.
Yang
Wengang
W
Achillion Pharmaceuticals, 300 George Street, New Haven, CT 06511, USA.
Sun
Yongnian
Y
Phadke
Avinash
A
Deshpande
Milind
M
Huang
Mingjun
M
D001562:Benzimidazoles / Q000737:chemistry / Q000494:pharmacology; D001581:Benzothiadiazines / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics*; D015394:Molecular Structure; D009154:Mutation; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism; D013698:Templates, Genetic; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects; D012324:RNA-Dependent RNA Polymerase
D001562:Benzimidazoles; D001581:Benzothiadiazines; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C031000:benzimidazole; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase