Novel Antiviral Compound shows in-vivo efficacy against Cytomegalovirus

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Title: Novel Antiviral Compound shows in-vivo efficacy against Cytomegalovirus
Creators: Capone, Jesse
Advisor: Cook, Charles
Issue Date: 2007-06
Abstract: Widespread use of Ganciclovir (GCV) therapy has led to resistant strains of cytomegalovirus (CMV), prompting development of new antiviral compounds. A novel duplex compound of Zidovudine and Foscarnet (N3) has shown excellent in-vitro activity against both GCV sensitive and resistant HCMV strains. To begin in-vivo efficacy studies, we chose to use a well-characterized murine model of CMV (MCMV) infection. We confirmed in-vitro activity of N3 against MCMV using infected fibroblasts. QRT-PCR demonstrated that N3 controlled in-vitro DNA replication at 48 or 72hrs pi. To test in-vivo efficacy, cohorts of BALB/c mice infected with 5 X 104 PFU Smith strain MCMV received daily intraperitoneal dosing of N3 (5-50mg/kg), Ganciclovir (GCV, 10mg/kg), Foscarnet (PFA, 45-90mg/kg), or saline. N3-50mg and GCV showed comparable reduction of salivary gland infectious virus titers 14 days post infection, while N3-5mg did not control virus titers. Quantitative PCR (QRT-PCR) showed that GCV treatment reduced viral DNA load in salivary glands, but N3 did not. Similarly, lungs showed no significant reduction in viral DNA load for N3-50mg. In contrast, N3 (all doses), PFA, and GCV similarly reduced hepatic viral DNA load compared to saline treated mice. Taken together, these data suggest some in-vivo antiviral effect of the novel N3 compound. Interestingly, in some tissues, N3 may inhibit viral growth without inhibiting DNA replication. Overall poor effect of N3 in organs outside the peritoneal cavity suggests a problem with drug bioavailability when administered via the intraperitoneal route. Further evaluation of N3 efficacy in-vivo and mechanism of action will be required. Advisor: Charles H. Cook
Series/Report no.: The Ohio State University. Department of Microbiology Honors Theses; 2007
Keywords: CMV
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Attribution-NonCommercial-NoDerivs 3.0 Unported