In vivo activity of pyrimidine-dispirotripiperaziniumin in the male guinea pig model of genital herpes

Abstract

Herpes Simplex Virus (HSV-2) is a risk factor in the transmission of human immunodeficiency virus. While treatments exist for HSV they are either not completely effective or have a single target. We have described a novel pyrimidyl-di(diazaspiroalkane) derivative called 3,3’-(2-methyl-5-nitropyrimidine-4,6-diyl)-3,12-bis-6,9-diazadiazoniadispiro [5.2.5.2]hexadecane tetrachloride dihydrochloride (PDSTP) that targets heparan sulfate on host cells and has broad spectrum antiviral activity and lacks cytotoxicity. In previous studies we have confirmed the antiviral activity in vitro and now present the results of in vivo testing. We demonstrated that 10% ointment or 10% gel containing PDSTP administered topically or injected subcutaneously (twice daily for 5 days) has a therapeutic effect in the guinea pig model of genital herpes induced by HSV-2. PDSTP reduces symptom intensity, time of lesion resolution, mean disease duration and infectivity of HSV-2. The strongest effect was observed for the PDSTP solution administered parenterally, while the minimum effect was shown in the experiments when 10% gel was applied onto the lesion foci. Further experiments were performed which showed all the dosage forms had efficacy which was dependent on treatment initiation time. PDSTP performed comparably well against clinical symptoms versus acyclovir. Both PDSTP and acyclovir have different mechanisms so future work to study the effect of combination treatment is warranted.