scholarly journals Treatment of chronic woodchuck hepatitis virus infection in the eastern woodchuck(marmota monax) with nucleoside analogues is predictive of therapy for chronic hepatitis B virus infection in humans

Hepatology ◽  
2000 ◽  
Vol 31 (5) ◽  
pp. 1165-1175 ◽  
Author(s):  
Brent E. Korba ◽  
Paul Cote ◽  
William Hornbuckle ◽  
Bud C. Tennant ◽  
John L. Gerin
Keyword(s):  
Chronic Hepatitis ◽  
Virus Infection ◽  
Hepatitis Virus ◽  
Nucleoside Analogues ◽  
Woodchuck Hepatitis Virus ◽  
Hepatitis B Virus Infection ◽  
Marmota Monax ◽  
Chronic Hepatitis B Virus ◽  
B Virus ◽  
Hepatitis Virus Infection

scholarly journals Antiviral Activities of Oral 1-O-Hexadecylpropanediol-3-Phosphoacyclovir and Acyclovir in Woodchucks with Chronic Woodchuck Hepatitis Virus Infection

2000 ◽  
Vol 44 (7) ◽  
pp. 1964-1969 ◽  
Author(s):  
Karl Y. Hostetler ◽  
James R. Beadle ◽  
William E. Hornbuckle ◽  
Christine A. Bellezza ◽  
Ilia A. Tochkov ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Virus Infection ◽  
Hepatitis B ◽  
Hepatitis Virus ◽  
Response To Therapy ◽  
Hydroxyl Group ◽  
Woodchuck Hepatitis Virus ◽  
Acyclovir Treatment ◽  
B Virus ◽  
Hepatitis Virus Infection

ABSTRACT Acyclovir triphosphate is a potent inhibitor of hepatitis B virus DNA polymerase, but acyclovir treatment provides no benefit in patients with hepatitis B virus infection. This is due in part to the fact that hepatitis B virus, unlike herpes simplex virus, does not code for a viral thymidine kinase which catalyzes the initial phosphorylation of acyclovir. We synthesized 1-O-octadecyl-sn-glycero-3-phospho (3-P)-acyclovir and found that it was highly active in reducing hepatitis B virus replication in 2.2.15 cells, while acyclovir was inactive. The greater antiviral activity of 1-O-octadecyl-sn-glycero-3-P-acyclovir appeared to be due to liver cell metabolism of the compound to acyclovir monophosphate (K. Y. Hostetler et al., Biochem. Pharmacol. 53:1815–1822, 1997). However, a closely related compound without a hydroxyl group at the sn-2 position of glycerol, 1-O-hexadecylpropanediol-3-P-acyclovir, was more active and selective in 2.2.15 cells in vitro. In this study, we treated woodchucks chronically infected with woodchuck hepatitis virus with increasing oral doses of 1-O-hexadecylpropanediol-3-P-acyclovir and assessed the response to therapy versus acyclovir or a placebo. At a dosage of 10 mg/kg of body weight twice a day, the test compound significantly inhibited viral replication in vivo, as indicated by a 95% reduction in serum woodchuck hepatitis virus DNA levels and by a 54% reduction in levels of woodchuck hepatitis virus replicative intermediates in the liver. Higher doses were somewhat less effective. In contrast, 20 mg of acyclovir/kg twice daily, a 5.3-fold-higher molar dosage, had no demonstrable activity against woodchuck hepatitis virus. Oral 1-O-hexadecylpropanediol-3-P-acyclovir appeared to be safe and effective in chronic woodchuck hepatitis virus infection.

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