Inhibition of the subgenomic hepatitis C virus replicon in huh-7 cells by 2'-deoxy-2'-fluorocytidine.
2'-Deoxy-2'-fluorocytidine (FdC) is a potent inhibitor of the hepatitis C virus RNA replicon in culture, and FdC-5'-triphosphate is an effective inhibitor of the NS5B polymerase. Dynamic profiling of cell growth in an antiviral assay showed that FdC caused cytostasis due to an S-phase arrest. These observations demonstrate that FdC treatment is affecting both a viral target and a cellular target.
Stuyver
Lieven J
LJ
Pharmasset, Inc., Tucker, Georgia 30084, USA.
McBrayer
Tamara R
TR
Whitaker
Tony
T
Tharnish
Phillip M
PM
Ramesh
Mangala
M
Lostia
Stefania
S
Cartee
Leanne
L
Shi
Junxing
J
Hobbs
Ann
A
Schinazi
Raymond F
RF
Watanabe
Kyoichi A
KA
Otto
Michael J
MJ
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001908:Diarrhea Viruses, Bovine Viral / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D012367:RNA, Viral / Q000096:biosynthesis* / Q000235:genetics*; D012093:Replicon / Q000187:drug effects* / Q000235:genetics*; D016196:S Phase / Q000187:drug effects; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D003841:Deoxycytidine; D004791:Enzyme Inhibitors; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C007251:2'-fluoro-2'-deoxycytidine