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Effects of Pyrimidine Derivatives on RNA-Dependent RNA Polymerase of Mengovirus-Infected Fogh and Lund (FL) cells

Academy of Sciences of the GDR, Research Centre for Molecular Biology and Medicine, Central Institute for Microbiology and Experimental Therapy, Jena, GDR

Two newly synthesized pyrimidine derivative were found to possess antiviral activity against Mengovirus in Fogh and Lund (FL) cells and in a cell-free system. The inhibitory effect on RNA-dependent RNA polymerase of Mengovirus-infected FL cells was assayed using ¹⁴C-UTP as precursor. Addition of 50 or 100 µM of the inhibitors in a cell-free system of crude enzyme and nucleoside triphosphate medium for 60 min incubation at 37 °C resulted in about 40 to 60% lower counting rates for drug-treated reaction mixtures. The analysis of the polymerase synthesis product (virus RNA extracted from the cell-free reaction mixture and deproteinized by the phenol-SDS method) was carried out by means of agarose-acrylamide gel electrophoresis. The main finding was a reduction of single-stranded Mengovirus RNA (RNase-sensitive and LiCl-precipitable). The rates of synthesis of the replicative intermediate (LiCl-precipitable) and the replicative form of RNA (LiCl-soluble) were not significantly influenced.

Received 3 March 1976; accepted 16 July 1976.