Combined antiviral effect of DNA inhibitors on Herpes simplex virus multiplication.

The inhibition of herpesvirus type 1 in cell cultures by seven inhibitors of DNA synthesis and by pactamycin was investigated by plaque inhibition in Vero cells with agarose overlay, and by yield reduction in one-step growth in HeLa cells. While the plaque inhibition method proved to be suitable to show inhibition by single substances, only the yield reduction procedure was reliable for investigating the interaction of two substances. Inhibition was evaluated by means of an inhibition quotient (number of PFU in uninhibited virus controls:number of PFU in test specimen); combined inhibition was related to results with single substances. Among the 28 substance pairs, 9 cases of indifference, 10 additive, and 9 synergistic interactions were found. Indifference was observed only with fluorodeoxyuridine and amethopterin as one of the partners, which by themselves inhibited herpesvirus multiplication incompletely.