Inhibition of Herpes Simplex Virus Infection in Tissue Culture by Trisodium Phosphonoformate 1

Summary

The present report describes the in vitro effect on herpes simplex virus (HSV) replication of trisodium phosphonoformate (PFA), a drug with low toxicity and which selectively inhibits the HSV induced DNA-polymerase and thus may have potential use in the treatment of HSV infection in man. The inhibitory effect of PFA on HSV replication was strictly dose-dependent and in the presence of 0.25 mM PFA the TCID₅₀ titers of HSV-1 and HSV-2 reference strains in green monkey kidney cells were decreased by 2 log units. The amount of virus inoculated or produced in the culture and the time for PFA-HSV interaction were factors influencing the virus inhibitory effect of PFA. None of 41 HSV-1 and 39 HSV-2 wild strains were resistant to the drug. However, passage of plaque purified HSV in the presence of 0.25 mM PFA resulted in appearance of mutants gradually more PFA resistant.