viroxime and arildone

Topics: Animals; Antiviral Agents; Benzimidazoles; Drug Resistance, Microbial; Echovirus Infections; Enterovirus; Enterovirus B, Human; Enterovirus Infections; Flavonoids; Humans; Ketones; Mice; Oximes; Picornaviridae; Picornaviridae Infections; Poliomyelitis; Poliovirus; Rats; Rhinovirus; Rhodanine; Sulfonamides

The existence of synergistic drug combinations against the in vitro replication of poliovirus type 1 (Mahoney) (PV-1) had been established in our previous work. The objective of the present study was to test the combined effects of the different drugs against another representative of the enterovirus genus, i.e. Coxsackievirus B1 (CBV-1). Dual combinations of enviroxime, disoxaril, arildone, PTU-23, HBB and S-7 were evaluated. The susceptibility of CBV-1 to the individual effects of the inhibitors was compared to that of PV-1. CBV-1 was more sensitive to enviroxime, S-7, PTU-23 and HBB and less sensitive to the effects of disoxaril and arildone. The effect of most dual drug combinations tested against CBV-1 replication was additive or synergistic. Enviroxime and S-7, enviroxime and PTU-23, disoxaril and HBB, disoxaril and PTU-23, arildone and HBB, arildone and PTU-23, S-7 and HBB revealed a strong synergistic effect. Synergy against CBV-1 replication was stronger as compared to that noted for the same drug combinations against PV-1 replication.

Topics: Antiviral Agents; Benzimidazoles; Cell Line; Drug Combinations; Drug Synergism; Enterovirus B, Human; Humans; Isoxazoles; Ketones; Oximes; Phenylthiourea; Pyrimidines; Sulfonamides; Virus Replication

To assess the possible interactions among picornavirus replication inhibitors, inhibitory effects of dual combinations of enviroxime, disoxaril, arildone, S-7, guanidine, PTU-23, and HBB on poliovirus type 1 (Mahoney) replication in FL cells were tested. Beforehand, the 50% inhibitory concentration (IC50) in the plaque inhibition test was been determined for each individual compound, i.e. enviroxime-0.2 micromol/l, disoxaril-0.3 micromol/l, arildone-2.7 micromol/l, (S-7)-100 micromol/l, guanidine-200 micromol/l, (PTU-23)-200 micromol/l, and HBB-300 micromol/l. Each of the dual combinations, in which enviroxime or HBB was one of the partners, showed synergistic or additive effects. Combining disoxaril with enviroxime, HBB or PTU-23 resulted in synergism, while combining it with guanidine, S-7 or arildone led to antagonism. Arildone showed additive or synergistic effects when combined with enviroxime, HBB and PTU-23, and antagonistic ones when combined with disoxaril, S-7 or guanidine. All dual combinations of PTU-23 were synergistic with the exception of the pair of PTU-23 + guanidine that was antagonistic. Guanidine had additive to synergistic interactions with HBB or enviroxime but antagonistic ones with disoxaril, arildone and PTU-23. Guanidine or PTU-23 when combined with S-7 showed an unusual effect - synergistic one with an antagonistic zone. The combinations of S-7 with enviroxime or HBB were synergistic but those with disoxaril or arildone were antagonistic. Research on interactions 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 action of those inhibitors.

Topics: Antiviral Agents; Benzimidazoles; Cell Line; Drug Combinations; Drug Interactions; Drug Synergism; Guanidine; Humans; Isoxazoles; Ketones; Oximes; Phenylthiourea; Poliovirus; Pyrimidines; Sulfonamides; Virus Replication