Inhibition of hepatitis B virus polymerase-activity by various agents. Transient expression of hepatitis B virus DNA in hepatoma cells as novel system for evaluation of antiviral drugs.
The effect of three putative antiviral drugs--aciclovir (acyclovir, CAS 59277-89-3), zidovudine (azidothymidine, CAS 30516-87-1) and sorangicin B (a macrocyclic lactone, CAS 100415-25-6)--on replication and gene expression of hepatitis B virus (HBV) was studied in HepG2 cells. Transfection of these cells with cloned circular HBV DNA resulted in the production and secretion of virions into the medium. When antiviral drugs were added in increasing concentrations (aciclovir at 0.5 microgram/ml to 150 micrograms/ml, zidovudine 0.1 microgram/ml to 30 micrograms/ml, sorangicin B 1 micrograms/ml to 30 micrograms/ml), the activity of the viral polymerase decreased in a dose-dependent manner. Production of viral proteins as measured by the secretion of HBsAg and HBeAg into the medium was unaffected, suggesting interference of these drugs with viral DNA/RNA synthesis. It is concluded that aciclovir, zidovudine and sorangicin B inhibit the replication of HBV. Furthermore, the cell system used in our study appears to be suitable for the rapid testing of antiviral drugs and their evaluation for possible studies in vivo.
Galle
P R
PR
Department of Internal Medicine, University of Heidelberg, Fed. Rep. of Germany.
Theilmann
L
L
D000212:Acyclovir / Q000494:pharmacology; D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D004279:DNA, Viral / Q000096:biosynthesis; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000201:enzymology*; D008114:Liver Neoplasms, Experimental / Q000201:enzymology; D019384:Nucleic Acid Synthesis Inhibitors; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000494:pharmacology
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D019384:Nucleic Acid Synthesis Inhibitors; C052000:sorangicin B; D015215:Zidovudine; D000212:Acyclovir