Oral efficacy of WIN 51711 in mice infected with human poliovirus

Abstract

WIN 51711, a new broad-spectrum anti-picornavirus agent, prevented the development of paralysis and subsequent death in mice infected intracerebrally with a lethal dose of human poliovirus type 2 (MEF strain). The prophylactic efficacy of intragastrically administered WIN 51711 was dose dependent over the 3.9- to 62.5-mg/kg (twice daily) dose range, with a minimal significantly effective dose of less than 15.6 mg/kg per dose (twice daily) (P less than 0.008). An oral four times a day dosage regimen initiated 48 h postinfection with WIN 51711 doses as low as 12.5 mg/kg was effective in significantly reducing poliovirus-induced paralysis and death compared with a placebo. Viral titers in the brains and spines of mice infected intracerebrally with 200 50% lethal doses of poliovirus were reduced by 3 to 5 log10 PFU/g in the WIN 51711-medicated group compared with placebo-medicated animals. The potent in vitro and in vivo anti-picornavirus activity of WIN 51711 makes it a potentially useful drug for the treatment of enterovirus infections in humans.