Combination Effects of Peramivir and Favipiravir against Oseltamivir-Resistant 2009 Pandemic Influenza A(H1N1) Infection in Mice
Authors:
Open Access
- 3 July 2014
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 9 (7) , e101325
Abstract
Antiviral drugs are being used for therapeutic purposes against influenza illness in humans. However, antiviral-resistant variants often nullify the effectiveness of antivirals. Combined medications, as seen in the treatment of cancers and other infectious diseases, have been suggested as an option for the control of antiviral-resistant influenza viruses. Here, we evaluated the therapeutic value of combination therapy against oseltamivir-resistant 2009 pandemic influenza H1N1 virus infection in DBA/2 mice. Mice were treated for five days with favipiravir and peramivir starting 4 hours after lethal challenge. Compared with either monotherapy, combination therapy saved more mice from viral lethality and resulted in increased antiviral efficacy in the lungs of infected mice. Furthermore, the synergism between the two antivirals, which was consistent with the survival outcomes of combination therapy, indicated that favipiravir could serve as a critical agent of combination therapy for the control of oseltamivir-resistant strains. Our results provide new insight into the feasibility of favipiravir in combination therapy against oseltamivir-resistant influenza virus infection.Keywords
This publication has 49 references indexed in Scilit:
- Combinations of favipiravir and peramivir for the treatment of pandemic influenza A/California/04/2009 (H1N1) virus infections in miceAntiviral Research, 2012
- Efficacy, Safety, and Pharmacokinetics of Intravenous Peramivir in Children with 2009 Pandemic H1N1 Influenza A Virus InfectionAntimicrobial Agents and Chemotherapy, 2012
- Effect of an Asparagine-to-Serine Mutation at Position 294 in Neuraminidase on the Pathogenicity of Highly Pathogenic H5N1 Influenza A VirusJournal of Virology, 2011
- Assessment of Pandemic and Seasonal Influenza A (H1N1) Virus Susceptibility to Neuraminidase Inhibitors in Three Enzyme Activity Inhibition AssaysAntimicrobial Agents and Chemotherapy, 2010
- Combinations of oseltamivir and peramivir for the treatment of influenza A (H1N1) virus infections in cell culture and in miceAntiviral Research, 2010
- Permissive Secondary Mutations Enable the Evolution of Influenza Oseltamivir ResistanceScience, 2010
- Effects of the Combination of Favipiravir (T-705) and Oseltamivir on Influenza A Virus Infections in MiceAntimicrobial Agents and Chemotherapy, 2010
- T-705 (favipiravir) activity against lethal H5N1 influenza A virusesProceedings of the National Academy of Sciences, 2009
- Intracellular metabolism of favipiravir (T-705) in uninfected and influenza A (H5N1) virus-infected cellsJournal of Antimicrobial Chemotherapy, 2009
- Injectable peramivir mitigates disease and promotes survival in ferrets and mice infected with the highly virulent influenza virus, A/Vietnam/1203/04 (H5N1)Virology, 2008