Antiviral effect of the combination of enviroxime and disoxaril on coxsackievirus B1 infection.

Effects of enviroxime and disoxaril, inhibitors of replication of some picornaviruses with known mechanisms of action, alone or in combination, on replication of coxsackievirus B1 (CVB1) in FL cells and on experimental CVB1 infection in newborn mice were tested. The combination of enviroxime and disoxaril resulted in vitro in a synergistic interaction. Both compounds were administered in vivo, alone or in combination, daily by subcutaneous (s.c.) route since the day of virus inoculation till the 5th day post inoculation (p.i.). Our findings about the in vivo antiviral effects of the individual compounds correlated with those of other authors, i.e. disoxaril significantly reduced the virus-induced death (the minimum 50% effective dose (ED50) was 12.5 mg/kg; P = 0.0037), while enviroxime was not effective even when applied at a dose as high as 100 mg/kg (P = 0.264). However, when both the substances were combined, the same protective effect was achieved with concentrations of disoxaril two to four times lower than those of the drug administered alone. In this way a higher selectivity ratio was achieved. Namely, the combination of 50 mg/kg enviroxime and 3.125-6.25 mg/kg disoxaril was synergistic. Along with reduction in mortality a marked delay in the course of the disease was observed.