Mode of interference of trisodium phosphonoformate (INN: foscarnet sodium), with influenza virus mRNA synthesis.
Foscarnet has previously been shown to inhibit influenza RNA polymerase activity. In this report the mode of inhibition of foscarnet has been investigated by enzyme-kinetic procedures and product analysis. Foscarnet shows noncompetitive inhibition with respect to ATP, CTP, and UTP, and a mixed inhibition with respect to GTP. In the presence of foscarnet the initiation of the mRNA synthesis can still occur, but the elongation is inhibited. The block of mRNA formation by foscarnet seems to occur after the synthesis of the 12-nucleotide-long conserved sequence found at the 5 prime end of the viral message.
D000818:Animals; D000998:Antiviral Agents / Q000633:toxicity*; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D017245:Foscarnet; D005914:Globins / Q000235:genetics; D009980:Influenza A virus / Q000187:drug effects / Q000235:genetics*; D007700:Kinetics; D009943:Organophosphorus Compounds / Q000633:toxicity*; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000633:toxicity*; D010761:Phosphorus Radioisotopes; D012333:RNA, Messenger / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects*
D000998:Antiviral Agents; D009943:Organophosphorus Compounds; D010761:Phosphorus Radioisotopes; D012333:RNA, Messenger; D017245:Foscarnet; D005914:Globins; D012321:DNA-Directed RNA Polymerases; D010746:Phosphonoacetic Acid