Specific Antiviral Activity of Pyrimidinedispirotripiperazinium Alone and in Combination with Acyclovir on a Herpes-Simplex-Virus Infection Model

Abstract

Efficacious antiviral analogs of viral nucleoside DNA-polymerase inhibitors are used to treat infections caused by herpes simplex virus (HSV) although their widespread use in clinical practice has caused drug-resistant HSV strains to develop. The drug substance pyrimidine-dispirotripiperazinium or 3,3-(2-methyl-5-nitropyrimidin-4,6-diyl)-bis-3,12-diaza-6,9-diazoniadispiro[5.2.5.2]hexadecane tetrachloride dihydrochloride (PDSTP) was previously synthesized by us and possessed high antiherpetic activity in vitro. The antiherpetic efficacy of the new drug substance was evaluated in vivo using a herpetic encephalitis mouse model and various treatment regimes (i.p. and peroral administration, monotherapy, combination therapy with acyclovir).