T-705 (favipiravir) activity against lethal H5N1 influenza A viruses

Proc Natl Acad Sci U S A. 2010 Jan 12;107(2):882-7. doi: 10.1073/pnas.0909603107. Epub 2009 Dec 22.


The neuraminidase inhibitors oseltamivir and zanamivi are used to treat H5N1 influenza. However, oseltamivir-resistant H5N1 viruses have been isolated from oseltamivir-treated patients. Moreover, reassortment between H5N1 viruses and oseltamvir-resistant human H1N1 viruses currently circulating could create oseltamivir-resistant H5N1 viruses, rendering the oseltamivir stockpile obsolete. Therefore, there is a need for unique and effective antivirals to combat H5N1 influenza viruses. The investigational drug T-705 (favipiravir; 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) has antiviral activity against seasonal influenza viruses and a mouse-adapted H5N1 influenza virus derived from a benign duck virus. However, its efficacy against highly pathogenic H5N1 viruses, which are substantially more virulent, remains unclear. Here, we demonstrate that T-705 effectively protects mice from lethal infection with oseltamivir-sensitive or -resistant highly pathogenic H5N1 viruses. Furthermore, our biochemical analysis suggests that T-705 ribofuranosyl triphosphate, an active form of T-705, acts like purines or purine nucleosides in human cells and does not inhibit human DNA synthesis. We conclude that T-705 shows promise as a therapeutic agent for the treatment of highly pathogenic H5N1 influenza patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amides / pharmacology*
  • Animals
  • Antiviral Agents / pharmacology*
  • Cell Line
  • Child
  • DNA Replication / drug effects
  • DNA-Directed DNA Polymerase / drug effects
  • DNA-Directed DNA Polymerase / metabolism
  • Dogs
  • Drug Resistance, Viral
  • Humans
  • Influenza A Virus, H5N1 Subtype / drug effects*
  • Influenza, Human / drug therapy*
  • Influenza, Human / mortality
  • Kidney
  • Kinetics
  • Lung / drug effects
  • Oseltamivir / pharmacology
  • Pyrazines / pharmacology*
  • Ribavirin / pharmacology


  • Amides
  • Antiviral Agents
  • Pyrazines
  • Oseltamivir
  • Ribavirin
  • DNA-Directed DNA Polymerase
  • favipiravir