Galle P R, Theilmann L
Department of Internal Medicine, University of Heidelberg, Fed. Rep. of Germany.
Arzneimittelforschung. 1990 Dec;40(12):1380-2.
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.
在HepG2细胞中研究了三种假定的抗病毒药物——阿昔洛韦（无环鸟苷，CAS 59277-89-3）、齐多夫定（叠氮胸苷，CAS 30516-87-1）和索拉吉星B（一种大环内酯，CAS 100415-25-6）对乙型肝炎病毒（HBV）复制和基因表达的影响。用克隆的环状HBV DNA转染这些细胞导致病毒粒子产生并分泌到培养基中。当以递增浓度添加抗病毒药物时（阿昔洛韦为0.5微克/毫升至150微克/毫升，齐多夫定为0.1微克/毫升至30微克/毫升，索拉吉星B为1微克/毫升至30微克/毫升），病毒聚合酶的活性呈剂量依赖性降低。通过培养基中HBsAg和HBeAg的分泌来衡量的病毒蛋白产生未受影响，这表明这些药物干扰了病毒DNA/RNA合成。得出的结论是，阿昔洛韦、齐多夫定和索拉吉星B抑制HBV的复制。此外，我们研究中使用的细胞系统似乎适用于抗病毒药物的快速检测及其在体内可能研究的评估。
