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The effect of 2′-fluoro-2′-deoxycytidine on herpes virus growth
Authors:F. Wohlrab  A.T. Jamieson  J. Hay  Rolf Mengel  W. Guschlbauer
Affiliation:1. Service de Biochemie, Bât. 142, Départment de Biologie, Centre d''Etudes Nucléaires de Saclay, F-91191-Gif-sur-Yvette Cedex France;2. Institute of Virology, University of Glasgow, Glasgow U.K.;3. Fachbereich Chemie, Universität Konstanz, D-75 Konstanz F.R.G.
Abstract:The effect of 2′-fluoro-2′-deoxycytidine (dCfl) on the growth of certain viruses of the herpes type was investigated. It is shown that the compound has considerable anti-viral activity against HSV-I, HSV-II, pseudorabies virus and equine abortion virus. It has an effect comparable to that of araC and is more efficient than br5dC, but less so than acyclovir. Experiments with thymidine kinase-negative strains of HSV-I indicated that dCfl was phosphorylated by the viral kinase, and its Km appears to be low and close to that of thymidine. Density gradient centrifugation enabled us to show that dCfl was incorporated into cellular and viral DNA and RNA. The cytotoxic activity of dCfl appears to be about 10-times smaller than that of araC. Removal of the nucleoside analog, washing and replacement with deoxycytidine reversed this effect, indicating rather a cytostatic than cytotoxic effect.
Keywords:Fluorodeoxycytidine  Anti viral activity  Cytostatic activity  Thymidine kinase  (Herpes virus)  HSV  herpes simplex virus  PsRV  pseudorabies virus  EAV  equine abortion virus  nucleoside abbreviations according to IUPAC-IUB  dCfl  2′-fluoro-2′-deoxycytidine  araC  cytosine arabinoside  5-iododeoxyuridine
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