Inhibitory effects of atropine, protamine, and their combination on hepatitis A virus replication in PLC/PRF/5 cells

Atropine, protamine, and the combination of these drugs were tested for their effects on hepatitis A virus (HAV) replication in cell culture. PLC/PRF/5 hepatoma cells were treated simultaneously with nontoxic concentrations of these drugs and inoculated with HAV strain CF 53 at several multiplicities of infection. The yields of infectious HAV after 4 and 15 days were markedly reduced by each drug, especially at the lowest multiplicity of infection. The activities of each drug were irreversible. Atropine was active when it was added as late as 2 h after inoculation with HAV. An anti-HAV effect was also induced by treating cells with atropine prior to inoculation. Protamine was active as late as 6 h postinoculation. The combination of atropine and protamine resulted in an enhanced anti-HAV effect. We concluded that these drugs affect undetermined, but separate, steps in the HAV replication cycle.