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Antimicrobial Agents and Chemotherapy, April 2002, p. 977-981, Vol. 46, No. 4
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.4.977-981.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

In Vitro and In Vivo Activities of Anti-Influenza Virus Compound T-705

Y. Furuta,1* K. Takahashi,1 Y. Fukuda,1 M. Kuno,1 T. Kamiyama,1 K. Kozaki,1 N. Nomura,1 H. Egawa,1 S. Minami,1 Y. Watanabe,1 H. Narita,1 and K. Shiraki2

Research Laboratories, Toyama Chemical Co., Ltd., 2-4-1 Shimookui,1 Department of Virology, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, Japan2

Received 29 June 2001/ Returned for modification 10 September 2001/ Accepted 27 December 2001

T-705 (6-fluoro-3-hydroxy-2-pyrazinecarboxamide) has been found to have potent and selective inhibitory activity against influenza virus. In an in vitro plaque reduction assay, T-705 showed potent inhibitory activity against influenza A, B, and C viruses, with 50% inhibitory concentrations (IC50s) of 0.013 to 0.48 µg/ml, while it showed no cytotoxicity at concentrations up to 1,000 µg/ml in Madin-Darby canine kidney cells. The selectivity index for influenza virus was more than 2,000. It was also active against a neuraminidase inhibitor-resistant virus and some amantadine-resistant viruses. T-705 showed weak activity against non-influenza virus RNA viruses, with the IC50s being higher for non-influenza virus RNA viruses than for influenza virus, and it had no activity against DNA viruses. Orally administered T-705 at 100 mg/kg of body weight/day (four times a day) for 5 days significantly reduced the mean pulmonary virus yields and the rate of mortality in mice infected with influenza virus A/PR/8/34 (3 x 102 PFU). These results suggest that T-705 may be a compound that is useful and highly selective against influenza virus infections and that has a mode of action different from those of commercially available drugs, such as amantadine, rimantadine, and neuraminidase inhibitors.

* Corresponding author. Mailing address: Research Laboratories, Toyama Chemical Co., Ltd., 2-4-1 Shimookui, Toyama, 930-8508, Japan. Phone: 81-76-431-8257. Fax: 81-76-431-8208. E-mail: YOUSUKE_FURUTA{at}toyama-chemical.co.jp.

Antimicrobial Agents and Chemotherapy, April 2002, p. 977-981, Vol. 46, No. 4
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.4.977-981.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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