DNA polymerase activity of hepatitis B virus particles: differential inhibition by -enantiomers of nucleotide analogs
| Autor: | Nanine A. VanDraanen, George Andrew Freeman, Ann Aulabaugh, Wayne H. Miller, George R. Painter, Lawrence R. Boone, Boyd Frank Leslie, Susan Mary Daluge, Jeanne E. Wilson, Michelle G. Davis |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Hepatitis B virus
DNA polymerase DNA-Directed DNA Polymerase medicine.disease_cause Virology medicine Emtricitabine Humans Thymine Nucleotides Nucleotide Polymerase Nucleic Acid Synthesis Inhibitors Pharmacology chemistry.chemical_classification biology Nucleoside analogue Nucleotides Zalcitabine Deoxyguanine Nucleotides Templates Genetic Nucleotidyltransferase Molecular biology Reverse transcriptase Biochemistry chemistry Isotope Labeling DNA Viral Deoxycytosine Nucleotides biology.protein Nucleoside medicine.drug |
| Zdroj: | Antiviral Research. 30:133-145 |
| ISSN: | 0166-3542 |
| Popis: | DNA polymerase activity was assayed in hepatitis B virus (HBV) and core particles isolated from chronic producer lines. The particle-associated DNA polymerase activity, which was found to be limited to incorporation of only a few nucleotides, was inhibited by the 5′-triphosphates of nucleoside analogs. The 1-β- l (1S,4R) and 1-β- d (1R,4S) enantiomers of antiviral nucleoside analogs were compared for the ability to inhibit incorporation of natural nucleoside triphosphates into the viral DNA. Previously, both enantiomers of several analogs were found to be substrates for human immunodeficiency virus type 1 reverse transcriptase (HIV RT); the 1-β- d enantiomers of some pairs were preferred as substrates. In contrast, the 1-β- l enantiomers of all pairs tested were the more potent inhibitors of labeled substrate incorporation into hepatitis B virus DNA; the concentration required to inhibit the incorporation of the natural substrate by 50% was 6-fold to several hundred-fold lower than the concentration of the 1-β- d enantiomer required for the same inhibitory effect. This preference for the 1-β- l enantiomers was observed for both RNA-directed synthesis in core particles and DNA-directed synthesis in viral particles. The observed antiviral effect of the nucleoside analogs in cell culture seemed to be limited chiefly by their phosphorylation in cells. |
| Databáze: | OpenAIRE |
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