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In Vitro and in Vivo Activities of T-705 and Oseltamivir against Influenza Virus

T-705 (6-fluoro-3-hydroxy-2-pyrazinecarboxamide) has a potent and selective inhibitory activity against influenza virus. We studied the effects of an infectious dose on the anti-influenza virus activities of T-705 and oseltamivir, a commercially available neuraminidase inhibitor, both in vitro and i...

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Published in:Antiviral chemistry & chemotherapy 2003-10, Vol.14 (5), p.235-241
Main Authors: Takahashi, Kazumi, Furuta, Yousuke, Fukuda, Yoshiko, Kuno, Masako, Kamiyama, Tomoko, Kozaki, Kyo, Nomura, Nobuhiko, Egawa, Hiroyuki, Minami, Shinzaburo, Shiraki, Kimiyasu
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Language:English
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Summary:T-705 (6-fluoro-3-hydroxy-2-pyrazinecarboxamide) has a potent and selective inhibitory activity against influenza virus. We studied the effects of an infectious dose on the anti-influenza virus activities of T-705 and oseltamivir, a commercially available neuraminidase inhibitor, both in vitro and in vivo. Plaque formation of influenza A/PR/8/34 virus was completely inhibited by 10 μg/ml of T-705 after 72 h incubation, whereas visible plaque formation was detected in the plate treated with GS 4071, the active form of oseltamivir (10 μg/ml). The antiviral activity of T-705 was not influenced by an increase in multiplicity of infection (MOI) from 0.0001 to 1, but that of GS 4071 was influenced in a yield reduction assay. No increase in viral yield was seen in either culture supernatant or cells after removal of T-705 (10 μg/ml) but, in contrast, productive infection recurred in culture supernatant and in cells after removal of GS 4071. In mice infected with a high challenge dose of influenza A/PR/8/34 virus, orally administered T-705 (200 and 400 mg/kg/day) completely prevented the death of mice and the survival rates of mice were significantly higher than those in mice treated with oseltamivir (P
ISSN:2040-2066
0956-3202
2040-2066
DOI:10.1177/095632020301400502