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Antimicrobial Agents and Chemotherapy, February 2004, p. 651-654, Vol. 48, No. 2
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.2.651-654.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Inhibition of the Subgenomic Hepatitis C Virus Replicon in Huh-7 Cells by 2'-Deoxy-2'-Fluorocytidine

Lieven J. Stuyver,1,{dagger} Tamara R. McBrayer,1 Tony Whitaker,1 Phillip M. Tharnish,1 Mangala Ramesh,1 Stefania Lostia,1 Leanne Cartee,1 Junxing Shi,1 Ann Hobbs,1 Raymond F. Schinazi,2 Kyoichi A. Watanabe,1 and Michael J. Otto1*

Pharmasset, Inc., Tucker, Georgia 30084,1 Department of Pediatrics, Emory School of Medicine/Veterans Affairs Medical Center, Decatur, Georgia 300332

Received 17 June 2003/ Returned for modification 4 September 2003/ Accepted 14 October 2003

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.

* Corresponding author. Mailing address: Pharmasset Inc., 1860 Montreal Rd., Tucker, GA 30084. Phone: (678) 395-0050. Fax: (678) 395-0030. E-mail: motto{at}pharmasset.com.

{dagger} Present address: Virco BVBA, Mechelen, Belgium.

Antimicrobial Agents and Chemotherapy, February 2004, p. 651-654, Vol. 48, No. 2
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.2.651-654.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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