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T-705 (Favipiravir) Activity against Lethal H5N1 Influenza a Viruses
Maki Kiso, Kazumi Takahashi, Yuko Sakai-Tagawa, Kyoko Shinya, Saori Sakabe, Quynh Mai Le, Makoto Ozawa, Yousuke Furuta, Yoshihiro Kawaoka and Mary K. Estes
Proceedings of the National Academy of Sciences of the United States of America
Vol. 107, No. 2 (Jan. 12, 2010), pp. 882-887
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/40535866
Page Count: 6
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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.
Proceedings of the National Academy of Sciences of the United States of America © 2010 National Academy of Sciences