Abstract
Sodium 5-aminosulfonyl-2,4-dichlorobenzoate (M12325) was evaluated for antiviral activity in tissue culture and infected mice. At concentrations ranging from 2.5 to 75.8 micrograms/ml, M12325 inhibited the cytopathic effects of 10 mean tissue culture infective doses of influenza virus A/WSN, A/FM, A/Kumamoto, and B/Great Lakes; parainfluenza virus; rhinovirus; echovirus; respiratory syncytial virus; and vesicular stomatitis virus. Concentrations up to 150 micrograms/ml did not inhibit the cytopathic effects of herpes simplex virus, vaccinia virus, or adenovirus. Concentrations up to 3,160 micrograms/ml did not inhibit the growth of MDCK, Vero, or HEL cells in culture. Single oral doses of M12325, ranging from 10 to 300 mg/kg, administered 1 h before and 1 h after challenge, reduced mortality in mice inoculated intranasally with influenza A/WSN virus. Twice daily oral doses for 14 days effected significant reductions in the mortality of mice infected intranasally with influenza A/WSN, A/FM, A/Kumamoto, and B/Great Lakes, and parainfluenza virus, but they were not effective in mice infected with herpes simplex virus. Multiple doses of 10 and 30 mg/kg, administered intraperitoneally, reduced lung consolidation and virus titer. M12325 was well tolerated in multiple doses up to 1 g/kg orally. These observations support the conclusions that M12325 has a broad spectrum of activity against RNA viruses in vitro and in vivo, selective toxicity, and a large margin of safety.
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