Effects of pyrimidine derivatives on RNA-dependent RNA polymerase of mengovirus-infected Fogh and Lund (FL) cells.
Two newly synthesized pyrimidine derivatives 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 muM of the inhibitors in a cell-free system of crude enzyme and nucleoside triphosphate medium for 60 min incubation at 37 degrees 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.
D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D002474:Cell-Free System; D008574:Mengovirus / Q000187:drug effects / Q000201:enzymology*; D011743:Pyrimidines / Q000494:pharmacology*; D012316:RNA Nucleotidyltransferases / Q000378:metabolism*; D012367:RNA, Viral / Q000096:biosynthesis; D012324:RNA-Dependent RNA Polymerase / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D011743:Pyrimidines; D012367:RNA, Viral; D012316:RNA Nucleotidyltransferases; D012324:RNA-Dependent RNA Polymerase