1. 1-705 (favipiravir) activity against lethal H5N1 influenza A viruses.
- Author
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Kiso, Maki, Takahashi, Kazumi, Sakai-Tagawa, Yuko, Shinya, Kyoko, Sakabe, Saori, Le, Quynh Mai, Ozawa, Makoto, Furuta, Yousuke, and Kawaoka, Yoshihiro
- Subjects
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INFLUENZA A virus, H5N1 subtype , *NEURAMINIDASE , *DRUG resistance in microorganisms , *ANTIVIRAL agents , *PYRAZINAMIDE , *INFLUENZA treatment - Abstract
The neuraminidase inhibitors oseltamivir and zanamivi are used to treat H5N1 influenza. However, oseltamivir-resistant H5N1 viruses have been isolated from oseltamivir-treated patients. Moreover, reassortment between H5N1 viruses and oseltamvir-resistant human H1N1 viruses currently circulating could create oseltamivirresistant H5N1 viruses, rendering the oseltamivir stockpile obsolete. Therefore, there is a need for unique and effective antivirals to combat H5N1 influenza viruses. The investigational drug T-705 (favipiravir; 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) has antiviral activity against seasonal influenza viruses and a mouseadapted H5N1 influenza virus derived from a benign duck virus. However, its efficacy against highly pathogenic H5N1 viruses, which are substantially more virulent, remains unclear. Here, we demonstrate that T-705 effectively protects mice from lethal infection with oseltamivir-sensitive or -resistant highly pathogenic H5N1 viruses. Furthermore, our biochemical analysis suggests that T-705 ribofuranosyl triphosphate, an active form of T-705, acts like purines or purine nucleosides in human cells and does not inhibit human DNA synthesis. We conclude that T-705 shows promise as a therapeutic agent for the treatment of highly pathogenic H5N1 influenza patients. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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