INHIBITION OF THE ENTEROVIRUSES THAT CAUSE ACUTE HEMORRHAGIC CONJUNCTIVITIS (AHC) BY BENZIMIDAZOLES - ENVIROXIME (LY-122772) AND ENVIRADONE (LY-127123)

Enviradone (EvirD, (E)-1-[(1-methylethyl) sulfonyl]-6-(1-phenyl-1-propenyl)-1H-benzimidazole-2-amine) and Enviroxime (EvirX, 2-amino-1-(isopropyl-sulfonyl)-6-benzimidazole phenyl ketone oxime) inhibited enterovirus 70 (EV70) and coxsackievirus A24 variant (CA24v) infection of conjunctival and laryngeal cells. On average, the continuous presence of 1-3 mu g of EvirD or EvirX/ml in cell cultures acutely infected with EV70 or CA24v inhibited virus production(> 2 log(10) reduction) and 100% of the viral cytopathogenic effect (CPE). The 50% CPE inhibitory dose (ID50) for EvirD and EvirX against 11 EV70 and 15 CA24v isolates ranged from 0.01 to 0.3 mu g and 0.01-0.65 mu g/ml, respectively. The mean ID50 for EvirD and EvirX against the 26 AHC viruses was 0.17 +/- 0.12 mu g and 0.13 +/- 0.14 mu g/ml, respectively. Pretreatment for 15 min with 3 mu g EvirX/ml or for 1-2 h with 3 mu g EvirD/ml protected conjunctival cells against viral CPE. The cells were resistant to infection for 1-2 h at 33 and 37 degrees C after removal of EvirD and EvirX. The addition of 10 mu g EvirD/ml up to 6 h or 10 mu g EvirX/ml 1-2 h after low multiplicity infection inhibited viral CPE. Ten-fold less EvirD inhibited EV70 when added to glioma cells 2 h before infection than when added 2 h after infection. Our results indicate that EvirX and EvirD inhibit AHC viruses in vitro at concentrations that are not cytotoxic and suggest that EvirX or EvirD may be prove useful against AHC.