. Recently, the inhibitory activity of WIN 51711 against a number of enterovirus and rhinovirus serotypes has been reported (10) with reduction in plaque formation and reduction in virus yield at concentrations below that which inhibits cell growth. In plaque reduction assays, concentrations of WIN 51711 in the range of 0.004 to 0.17 ,ug/ml caused a 50% reduction in plaque formation for the enteroviruses tested. Generally, the rhinoviruses tested in plaque reduction assays were less sensitive to WIN 51711 than were the enteroviruses. However, the majority of the 33 serotypes which were tested showed a 50% reduction in plaque formation at less than 1 ,ug of WIN 51711 per ml (2.9 ,uM 433, 1984).Preliminary data presented here indicate that WIN 51711 exerts its virus-specific activity through the inhibition of an early event in the replication of rhinovirus and poliovirus and that the molecular basis of this mechanism is the inhibition of the virion uncoating process. Drug-resistant poliovirus type 2 variants were selected by picking plaques from plates infected with poliovirus in the presence of 1.0 and 0.1 ,ug of WIN 51711 per ml. The viruses isolated from plaques that developed in the presence of drug were passaged three times in HeLa (Ohio) monolayer cultures in the presence of 1.0 and 0.1 ,ug/ml and were designated rCl-1.0y and rCl-0.1y, respectively. These resistant variant stocks were stored at -70°C after testing for sensitivity to WIN 51711.
MATERIALS AND METHODS
VirusesVirus titrations were determined by plaque assay on day-old confluent HeLa (Ohio) monolayer cultures in sixwell cluster plates (Costar, Cambridge, Mass.