NDLI: In vitro activity of favipiravir and neuraminidase inhibitor combinations against oseltamivir-sensitive and oseltamivir-resistant pandemic influenza A (H1N1) virus

Content Provider	Springer Nature Link
Author	Tarbet, E. Bart Vollmer, Almut H. Hurst, Brett L. Barnard, Dale L. Furuta, Yousuke Smee, Donald F.
Copyright Year	2013
Abstract	Few anti-influenza drugs are licensed in the United States for the prevention and therapy of influenza A and B virus infections. This shortage, coupled with continuously emerging drug resistance, as detected through a global surveillance network, seriously limits our anti-influenza armamentarium. Combination therapy appears to offer several advantages over traditional monotherapy in not only delaying development of resistance but also potentially enhancing single antiviral activity. In the present study, we evaluated the antiviral drug susceptibilities of fourteen pandemic influenza A (H1N1) virus isolates in MDCK cells. In addition, we evaluated favipiravir (T-705), an investigational drug with a broad antiviral spectrum and a unique mode of action, alone and in dual combination with the neuraminidase inhibitors (NAIs) oseltamivir, peramivir, or zanamivir, against oseltamivir-sensitive pandemic influenza A/California/07/2009 (H1N1) and oseltamivir-resistant A/Hong Kong/2369/2009 (H1N1) virus. Mean inhibitory values showed that the tested virus isolates remained sensitive to commonly used antiviral drugs, with the exception of the Hong Kong virus isolate. Drug dose-response curves confirmed complete drug resistance to oseltamivir, partial sensitivity to peramivir, and retained susceptibility to zanamivir and favipiravir against the A/Hong Kong/2369/2009 virus. Three-dimensional analysis of drug interactions using the MacSynergyTM II program indicated an overall synergistic interaction when favipiravir was combined with the NAIs against the oseltamivir-sensitive influenza virus, and an additive effect against the oseltamivir-resistant virus. Although the clinical relevance of these drug combinations remains to be evaluated, results obtained from this study support the use of combination therapy with favipiravir and NAIs for treatment of human influenza virus infections.
Starting Page	1279
Ending Page	1291
Page Count	13
File Format	PDF
ISSN	03048608
Journal	Archives of Virology
Volume Number	159
Issue Number	6
e-ISSN	14328798
Language	English
Publisher	Springer Vienna
Publisher Date	2013-12-06
Publisher Place	Vienna
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Virology Medical Microbiology Infectious Diseases
Content Type	Text
Resource Type	Article
Subject	Virology Medicine

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