The chemotherapy of variola major infection.

In view of earlier work which suggested that certain derivatives of isatin beta-thiosemicarbazone might be of possible clinical use in smallpox infections, several such derivatives have been tested for antiviral effect in infant mice inoculated intracerebrally with up to 10(3) LD(50) (up to 10(6.5) pock-forming units) of the Harvey strain of variola major virus.Survival of 100% was obtained in mice treated twice daily with N-methylisatin beta-thiosemicarbazone in a dose level of 10 mg/kg, isatin beta-thiosemicarbazone in a dose level of 25 mg/kg and 7-methylisation beta-thiosemicarbazone at 10 mg/kg, the treatment beginning immediately after infection. No evidence of toxicity was observed at these dose levels. At lower dose levels of these and other related compounds complete protection was not obtained, but a chemotherapeutic effect was demonstrated by a prolongation of the mean survival time. Mice which had survived variola infection after treatment with an adequate dose of chemotherapeutic agent were immune when challenged with 10(5) pock-forming units of rabbitpox virus.