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

Effects of enviroxime and disoxaril, inhibitors of replication of some pico rnaviruses with known mechanisms of action, alone or in combination, on rep lication of coxsackievirus B1 (CVB1) in FL cells and on experimental CVB1 i nfection in newborn mice were tested. The combination of enviroxime and dis oxaril 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 5(th) day post inoculati on (p.i.). Our findings about the in vivo antiviral effects of the individu al compounds correlated with those of other authors, i.e, disoxaril signifi cantly reduced the virus-induced death (the minimum 50% effective dose (ED5 0) was 12.5 mg/kg; P = 0.0037), while enviroxime was not effective even whe n 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 con centrations of disoxaril two to four times lower than those of the drug adm inistered alone. In this way a higher selectivity ratio was achieved. Namel y, the combination of 50 mg/kg enviroxime and 3.125-6.25 mg/kg disoxaril wa s synergistic. Along with reduction in mortality a marked delay in the cour se of the disease was observed.