title: Synergistic combinations of favipiravir and oseltamivir against wild-type pandemic and oseltamivir-resistant influenza A virus infections in mice.
abstract: OBJECTIVE
  Favipiravir and oseltamivir are antiviral compounds used for the treatment of influenza infections. We have aimed to investigate the efficacy of the compounds in combination to treat influenza H1N1 virus infections in mice.
  
  
  METHODS
  Mice infected with pandemic influenza A/California/04/2009 (H1N1pdm) virus or an oseltamivir-resistant (H275Y neuraminidase mutation) influenza A/Mississippi/ 3/2001 (H1N1) virus were treated orally with inhibitors twice a day for 5 days starting 4 h after infection.
  
  
  RESULTS
  Complete protection from death was afforded by favipiravir treatments of 100 mg/kg/day, but lower doses were less effective. Combinations of oseltamivir (1 and 3 mg/kg/day) with favipiravir (3, 10 and 30 mg/kg/day) resulted in a synergistic improvement in survival rates against H1N1pdm infections. Significant reductions in lung virus titers also occurred. Against the H275Y virus infection, oseltamivir alone was only 30% protective from death at 100 mg/kg/day, but combinations of the two compounds produced a synergistic improvement in survival rate.
  
  
  CONCLUSIONS
  The utility of treating H1N1 influenza virus infections with oseltamivir and favipiravir in combination has been established.
authors.affiliation: Institute for Antiviral Research, Department of Animal, Dairy & Veterinary Sciences, Utah State University, Logan, UT, USA.
authors.forename: Donald F
authors.initials: DF
authors.lastname: Smee
authors.affiliation: Institute for Antiviral Research, Department of Animal, Dairy & Veterinary Sciences, Utah State University, Logan, UT, USA.
authors.forename: E Bart
authors.initials: EB
authors.lastname: Tarbet
authors.affiliation: Toyama Chemical Company, Tokyo, Japan.
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Furuta
authors.affiliation: Institute for Antiviral Research, Department of Animal, Dairy & Veterinary Sciences, Utah State University, Logan, UT, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Morrey
authors.affiliation: Institute for Antiviral Research, Department of Animal, Dairy & Veterinary Sciences, Utah State University, Logan, UT, USA.
authors.forename: Dale L
authors.initials: DL
authors.lastname: Barnard
keywords: H1N1; T-705; antiviral; drug combination; drug resistance; favipiravir; influenza; mice; oseltamivir; treatment