AIM: 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. MATERIALS & 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. CONCLUSION: The utility of treating H1N1 influenza virus infections with oseltamivir and favipiravir in combination has been established.
AIM: 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. MATERIALS & 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 H275Yvirus 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. CONCLUSION: The utility of treating H1N1 influenza virus infections with oseltamivir and favipiravir in combination has been established.
Entities:
Keywords:
H1N1; T-705; antiviral; drug combination; drug resistance; favipiravir; influenza; mice; oseltamivir; treatment
Authors: Larisa V Gubareva; A Angelica Trujillo; Margaret Okomo-Adhiambo; Vasiliy P Mishin; Varough M Deyde; Katrina Sleeman; Ha T Nguyen; Tiffany G Sheu; Rebecca J Garten; Michael W Shaw; Alicia M Fry; Alexander I Klimov Journal: Antivir Ther Date: 2010
Authors: Elena A Govorkova; Tatiana Baranovich; Patrick Seiler; Jianling Armstrong; Andrew Burnham; Yi Guan; Malik Peiris; Richard J Webby; Robert G Webster Journal: Antiviral Res Date: 2013-02-28 Impact factor: 5.970
Authors: Donald F Smee; Brett L Hurst; Min-Hui Wong; Kevin W Bailey; E Bart Tarbet; John D Morrey; Yousuke Furuta Journal: Antimicrob Agents Chemother Date: 2009-11-09 Impact factor: 5.191
Authors: Jack T Nguyen; Donald F Smee; Dale L Barnard; Justin G Julander; Matthew Gross; Menno D de Jong; Gregory T Went Journal: PLoS One Date: 2012-01-23 Impact factor: 3.240
Authors: Terry G Besselaar; Dhamari Naidoo; Amelia Buys; Vicky Gregory; Jo McAnerney; Jack M Manamela; Lucille Blumberg; Barry D Schoub Journal: Emerg Infect Dis Date: 2008-11 Impact factor: 6.883
Authors: Bindumadhav M Marathe; Sook-San Wong; Peter Vogel; Fernando Garcia-Alcalde; Robert G Webster; Richard J Webby; Isabel Najera; Elena A Govorkova Journal: Sci Rep Date: 2016-05-25 Impact factor: 4.379
Authors: Ana I de Ávila; Isabel Gallego; Maria Eugenia Soria; Josep Gregori; Josep Quer; Juan Ignacio Esteban; Charles M Rice; Esteban Domingo; Celia Perales Journal: PLoS One Date: 2016-10-18 Impact factor: 3.240
Authors: Louise Ormond; Ping Liu; Sebastian Matuszewski; Nicholas Renzette; Claudia Bank; Konstantin Zeldovich; Daniel N Bolon; Timothy F Kowalik; Robert W Finberg; Jeffrey D Jensen; Jennifer P Wang Journal: Genome Biol Evol Date: 2017-07-01 Impact factor: 3.416
Authors: Mohammed Uddin; Farah Mustafa; Tahir A Rizvi; Tom Loney; Hanan Al Suwaidi; Ahmed H Hassan Al-Marzouqi; Afaf Kamal Eldin; Nabeel Alsabeeha; Thomas E Adrian; Cesare Stefanini; Norbert Nowotny; Alawi Alsheikh-Ali; Abiola C Senok Journal: Viruses Date: 2020-05-10 Impact factor: 5.048