T-705 (Favipiravir) suppresses tumor necrosis factor α production in response to influenza virus infection: A beneficial feature of T-705 as an anti-influenza drug

Acta Virol. 2017;61(1):48-55. doi: 10.4149/av_2017_01_48.


Influenza virus infection induces the production of various cytokines, which play important roles in the pathogenesis of infection. Among the cytokines induced by influenza, tumor necrosis factor α (TNF-α) production has been correlated with the severity of lung lesions. We investigated the effects of T-705 (Favipiravir, 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) on cytokine production due to influenza virus infection in vitro and in vivo, compared with oseltamivir or GS 4071, an active form of oseltamivir. TNF-α production in mouse macrophage-derived P388D1 cells infected with the influenza virus was lower following treatment with T-705 at concentrations of 0.3 to 100 µg/ml than treatment with GS 4071 at the same concentrations. The effect of treatment with T-705 on the cytokine production induced by the influenza virus infection was investigated in mouse influenza virus infection model. At 48 h post-infection (p.i.) T-705 significantly suppressed the viral load in the lungs and TNF-α production in the airways of infected mice even when viral loads were high. Furthermore, T-705 suppressed only TNF-α production from the early phase of infection. In this study, T-705 showed the antiviral activity of reducing pulmonary viral load compared with oseltamivir, thereby suppressing the TNF-α production. This feature of T-705 is benefit against severe influenza infection.

Keywords: influenza; T-705 (Favipiravir); TNF-α; cytokines; viral load..

MeSH terms

  • Amides / therapeutic use*
  • Animals
  • Antiviral Agents / therapeutic use*
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / virology
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation
  • Influenza A Virus, H1N1 Subtype*
  • Mice
  • Orthomyxoviridae Infections / drug therapy*
  • Orthomyxoviridae Infections / virology
  • Oseltamivir / therapeutic use
  • Pyrazines / therapeutic use*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism*
  • Viral Load


  • Amides
  • Antiviral Agents
  • Pyrazines
  • Tumor Necrosis Factor-alpha
  • Oseltamivir
  • favipiravir