PTU-23, an effective in vivo wide-range enterovirus inhibitor, suppresses the reproduction of encephalomyocarditis (EMC) virus in Krebs-II
ascites carcinoma cells at concentrations of 20-50 micrograms/ml, not affecting the cellular synthetic processes. The virus-specific
RNA synthesis is distinctly inhibited. The studies on the kinetics of this effect point to its leading role in the inhibitory action the compound exerts on the production of infectious virions. The sedimentation profile in
sucrose density gradient of the
viral RNA isolated from PTU-23-treated cells by
phenol extraction shows a clear inhibition of the synthesis of the single-stranded (ss) 37S
RNA and to a lesser extent of the double-stranded (ds, RF) 20S
RNA. The effect of the inhibitor on the
RNA-dependent RNA polymerase in a
cell-free RNA-synthesizing system has been studied, using an an
enzyme preparation the 40000 g fraction of a nuclear-free extract from infected Krebs-II cells, containing the
enzyme bound to the endogenous
RNA template. It is established that the compound does, not affect the synthesis of the
enzyme which could be probably explained by the incomplete (45-70%) inhibition of the
viral RNA synthesis, its translatory function remaining unperturbed. The observed insignificant inhibition (20-26%) of the
enzyme activity during the application of the inhibitor to the
RNA-synthesizing reaction mixture cannot explain its effect on the
viral RNA synthesis. An interaction of
PTU-23 with another virus-specific
protein component of the replication complex is suggested.