Mechanism of action of T-705 against influenza virus

Antimicrob Agents Chemother. 2005 Mar;49(3):981-6. doi: 10.1128/AAC.49.3.981-986.2005.


T-705, a substituted pyrazine compound, has been found to exhibit potent anti-influenza virus activity in vitro and in vivo. In a time-of-addition study, it was indicated that T-705 targeted an early to middle stage of the viral replication cycle but had no effect on the adsorption or release stage. The anti-influenza virus activity of T-705 was attenuated by addition of purines and purine nucleosides, including adenosine, guanosine, inosine, and hypoxanthine, whereas pyrimidines did not affect its activity. T-705-4-ribofuranosyl-5'-triphosphate (T-705RTP) and T-705-4-ribofuranosyl-5'-monophosphate (T-705RMP) were detected in MDCK cells treated with T-705. T-705RTP inhibited influenza virus RNA polymerase activity in a dose-dependent and a GTP-competitive manner. Unlike ribavirin, T-705 did not have an influence on cellular DNA or RNA synthesis. Inhibition of cellular IMP dehydrogenase by T-705RMP was about 150-fold weaker than that by ribavirin monophosphate, indicating the specificity of the anti-influenza virus activity and lower level of cytotoxicity of T-705. These results suggest that T-705RTP, which is generated in infected cells, may function as a specific inhibitor of influenza virus RNA polymerase and contributes to the selective anti-influenza virus activity of T-705.

MeSH terms

  • Amides / pharmacology*
  • Antiviral Agents / pharmacology*
  • Chromatography, High Pressure Liquid
  • DNA / biosynthesis
  • DNA-Directed RNA Polymerases / antagonists & inhibitors
  • IMP Dehydrogenase / antagonists & inhibitors
  • Orthomyxoviridae / drug effects*
  • Pyrazines / pharmacology*
  • RNA / biosynthesis


  • Amides
  • Antiviral Agents
  • Pyrazines
  • RNA
  • DNA
  • IMP Dehydrogenase
  • DNA-Directed RNA Polymerases
  • favipiravir