Danuta Madej

Half-Life of the Duck Hepatitis B Virus Covalently Closed Circular DNA Pool In Vivo following Inhibition of Viral Replication

ABSTRACT Covalently closed circular DNA (cccDNA) is a crucial intermediate in the replication of hepadnaviruses. We inhibited the replication of duck hepatitis B virus in congenitally infected ducks with a combination of lamivudine and a dideoxyguanosine prodrug. Inhibition of viral replication should prevent renewal of the cccDNA pool, and its decay was measured in liver biopsy samples collected over a 5-month period. In three ducks, the cccDNA pools declined exponentially, with half-lives ranging from 35 to 57 days. In two others, the pools declined exponentially for about 70 days but then stabilized at about 6 copies/diploid genome. The selection of drug-resistant virus mutants is an unlikely explanation for this unexpected stabilization of cccDNA levels. Liver sections stained for the cell division marker PCNA showed that animals in which cccDNA loss was continuous had significantly greater numbers of PCNA-positive nuclei than did those animals in which cccDNA levels had plateaued.

Synthesis, Transformation Chemistry, and Biological Activity of Guanine Nucleosides and Analoges

Abstract Regiospecific (9-) and regioselective (7-) coupling procedures have been developed with easily prepared guanine derivatives. Acyclovir and 9-(D-pentofuranosyl)guanine nucleosides have been prepared without observed formation of 7-isomers. Guanosine has been functionalized and transformed into a variety of base and/or sugar modified analogues. Potent activity against HIV and a hepadnavirus has been found.