Inhibition of vesicular stomatitis virus RNA synthesis by 2',3'-dideoxycytidine 5'-triphosphate

The ability of the compound 2',3'-dideoxycytidine 5'-triphosphate (ddCTP) to serve as an inhibitor of viral RNA synthesis was examined using an in vitro system that supports vesicular stomatitis virus (VSV) protein synthesis, transcription and replication. Viral RNA synthesis was inhibited by 87 and 98% of control, respectively, in reactions containing 1 mM- and 10 mM-ddCTP in place of CTP. VSV RNA replication and transcription were inhibited equally by ddCTP. At a concentration of 1 mM-ddCTP, there was no inhibitory effect on viral protein synthesis; at 10 mM-ddCTP, total protein synthesis was inhibited by 30% as compared to control reactions. The presence of ddCTP had no effect on the size or relative molar amounts of each protein synthesized as analysed by electrophoresis on polyacrylamide gels. This is the first report describing a compound that will inhibit VSV RNA synthesis in vitro without compromising the concurrent synthesis and modification of proteins.