Journal of Antimicrobial Chemotherapy (1987) 19, 815-822
© 1987 The British Society for Antimicrobial Chemotherapy
research-article |
The in-vitro and in-vivo efficacy of cisplatin and analogues in the treatment of herpes simplex virus-II infections
aDivision of Infectious Diseases and Hospital Epidemiology, Henry Ford Hospital Detroit, Michigan bDepartment of Chemistry, Oakland University Rochester, Michigan, U.S.A. and Delta Metals, Inc., Rochester, Michigan, U.S.A.
accepted 10 December 1986
The antitumour effect of cisplatin results from cross-linking and disruption of DNA when it binds to DNA bases, especially cytosine and guanine. Since herpes simplex virus (HSV) has a high cytosine and guanine content, cisplatin might be expected to have an antiviral effect against HSV. The 50% inhibitory concentration of cisplatin for HSV-II was 0.06 mg/1. Six of ten platinum analogues had 50% inhibition of plaques at
10 mg/1. We evaluated the in-vivo activity of cisplatin against the MS strain of HSV-II in the mouse genital HSV model. Mice were treated either intraperitoneally or intravaginally beginning at 3 or 51 h after inoculation. In the intraperitoneally treated groups infection rates were lower, but not significantly; 4 of 15 in the 3-h and 7 of 15 in the 51-h group, compared to 9 of 15 in the untreated control group (P>0.18, chi-square test). Intravaginal cisplatin demonstrated a significant reduction of the infection rate from 10 of 15 untreated controls, compared to 5 of 18 in the 3-h and 5 of 17 in the 51-h group (P < 0.05, chi-square test). No toxic effects of intravaginal cisplatin were seen in uninfected mice. These studies suggest that platinum containing drugs warrant further evaluation as a new class of antiviral agents with activity against HSV.