The in-vitro and in-vivo efficacy of cisplatin and analogues in the treatment of herpes simplex virus-II infections

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% inhi...

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Bibliographic Details
Published in:Journal of antimicrobial chemotherapy 1987-06, Vol.19 (6), p.815-822
Main Authors: Snyder, Michael B., Saravolatz, Louis D., Markowitz, Norman, Pohlod, Donald, Taylor, R. Craig, Ward, Sarah G.
Format: Article
Language:English
Subjects:
Animals
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antiviral agents
Biological and medical sciences
Cisplatin - pharmacology
Cisplatin - toxicity
Female
Herpes Simplex - drug therapy
herpes simplex virus 2
Medical sciences
Mice
Pharmacology. Drug treatments
Structure-Activity Relationship
Virus Replication - drug effects
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Summary: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.
ISSN:0305-7453
1460-2091
DOI:10.1093/jac/19.6.815