In vitro inhibitory effects of dual combinations of picornavirus replication inhibitors

To assess the possible interactions among picornavirus replication inhibito rs, inhibitory effects of dual combinations of enviroxime, disoxaril, arild one, S-7, guanidine, PTU-23, and HBB on poliovirus type 1 (Mahoney) replica tion in FL cells were tested. Beforehand, the 50% inhibitory concentration (IC50) in the plaque inhibition test was been determined for each individua l compound, i.e. enviroxime - 0.2 mu mol/l, disoxaril - 0.3 mu mol/l, arild one - 2.7 mu mol/l, S-7 - 100 mu mol/l, guanidine - 200 mu mol/l, PTU-23 -2 00 mu mol/l, and HBB - 300 mu mol/l. Each of the dual combinations, in whic h enviroxime or HBB was one of the partners, showed synergistic or additive effects. Combining disoxaril with enviroxime, HBB or PTU-23 resulted in sy nergism, while combining it with guanidine, S-7 or arildone led to antagoni sm. Arildone showed additive or synergistic effects when combined with envi roxime, HBB and PTU-23, and antagonistic ones when combined with disoxaril, S-7 or guanidine. All dual combinations of PTU-23 were synergistic with th e exception of the pair of PTU-23 + guanidine that was antagonistic. Guanid ine had additive to synergistic interactions with HBB or enviroxime but ant agonistic ones with disoxaril, arildone and PTU-23. Guanidine or PTU-23 whe n combined with S-7 showed an unusual effect - synergistic one with an anta gonistic zone. The combinations of S-7 with enviroxime or HBB were synergis tic but those with disoxaril or arildone were antagonistic. Research on int eractions of picornavirus replication inhibitors could possibly contribute to the development of efficient chemotherapy of infectious diseases caused by picornaviruses as well as to the better understanding of the mode of aci :ion of those inhibitors.