Antiviral properties, metabolism, and pharmacokinetics of a novel azolo-1,2,4-triazine-derived inhibitor of influenza A and B virus replication.

Influenza viruses of types A and B cause periodic pandemics in the human population. The antiviral drugs approved to combat influenza virus infections are currently limited. We have investigated an effective novel inhibitor of human influenza A and B viruses, triazavirine [2-methylthio-6-nitro-1,2,4-triazolo[5,1-c]-1,2,4-triazine-7(4I)-one] (TZV). TZV suppressed the replication of influenza virus in cell culture and in chicken chorioallantoic membranes, and it protected mice from death caused by type A and B influenza viruses. TZV was also effective against a rimantadine-resistant influenza virus strain and against avian influenza A virus H5N1 strains. The pharmacokinetic parameters and bioavailability of TZV were calculated after the administration of TZV to rabbits. The TZV metabolite AMTZV [2-methylthio-6-amino-1,2,4-triazolo[5,1-s]-1,2,4-triazin(e)-7(4I)-one] was discovered in IAK 293T and Huh7 cell cultures, a liver homogenate, and rabbit blood after intragastric administration of TZV. AMTZV was nontoxic and inactive as an inhibitor of influenza virus in cell culture. Most likely, this metabolite is a product of TZV elimination.
AuthorsInna Karpenko, Sergey Deev, Oleg Kiselev, Valerey Charushin, Vladimir Rusinov, Eugeney Ulomsky, Ella Deeva, Dmitry Yanvarev, Alexander Ivanov, Olga Smirnova, Sergey Kochetkov, Oleg Chupakhin, Marina Kukhanova
JournalAntimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 54 Issue 5 Pg. 2017-22 (May 2010) ISSN: 1098-6596 [Electronic] United States
PMID20194696 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antiviral Agents
  • Azoles
  • Triazines
  • triazavirin
  • Animals
  • Antiviral Agents (chemistry, pharmacokinetics)
  • Azoles (chemistry, pharmacokinetics)
  • Disease Models, Animal
  • Dogs
  • Drug Design
  • Hepatocytes (cytology, virology)
  • Humans
  • Influenza A virus (drug effects, growth & development)
  • Influenza B virus (drug effects, growth & development)
  • Injections, Intravenous
  • Kidney (cytology)
  • Mice
  • Mice, Inbred CBA
  • Orthomyxoviridae Infections (drug therapy)
  • Rabbits
  • Stomach
  • Triazines (chemistry, pharmacokinetics)
  • Virus Replication (drug effects)

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