title: 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.
abstract: 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.
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.forename: T
authors.initials: T
authors.lastname: Kamiyama
authors.forename: T
authors.initials: T
authors.lastname: Daikoku
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: N
authors.initials: N
authors.lastname: Nomura
authors.forename: M
authors.initials: M
authors.lastname: Kurokawa
authors.forename: K
authors.initials: K
authors.lastname: Shiraki
mesh_terms: D000577:Amides / Q000627:therapeutic use*; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000821:virology; D045744:Cell Line, Tumor; D005260:Female; D005786:Gene Expression Regulation; D053118:Influenza A Virus, H1N1 Subtype; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000821:virology; D053139:Oseltamivir / Q000627:therapeutic use; D011719:Pyrazines / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D019562:Viral Load
chemical_list: D000577:Amides; D000998:Antiviral Agents; D011719:Pyrazines; D014409:Tumor Necrosis Factor-alpha; D053139:Oseltamivir; C462182:favipiravir
keywords: influenza; T-705 (Favipiravir); TNF-α; cytokines; viral load.