Löfgren B, Nordenfelt E, Oberg B
Department of Medical Microbiology, University of Lund, Sweden.
Antiviral Res. 1989 Dec;12(5-6):301-10. doi: 10.1016/0166-3542(89)90057-0.
The DNA polymerase of hepadnaviruses has two different functions during virus replication. It acts both as an RNA-dependent DNA polymerase (reverse transcriptase) and as a DNA-dependent DNA polymerase. Duck hepatitis B virus (DHBV) preparations were used to investigate the inhibitory effects of selected compounds on these two enzyme activities. The reverse transcriptase activity was represented by an actinomycin D-resistant, phosphonoformate-sensitive DNA polymerase activity isolated from DHBV-infected duck livers. DHBV from serum was used as the source of the DNA-dependent DNA polymerase activity. Pyrophosphate and nucleoside triphosphate analogs were assayed for their inhibitory effects on the two enzyme preparations. A marked inhibition was obtained with 3'-fluoro-2',3'-dideoxythymidine 5'-triphosphate, acyclovir triphosphate, 2',3'-dideoxythymidine 5'-triphosphate, 2',3'-dideoxyguanosine 5'-triphosphate and 2',3'-dideoxythymidine 5'-triphosphate. The two thymidine analog triphosphates showed a markedly lower inhibitory effect on the reverse transcriptase activity than on the DNA-dependent DNA polymerase activity. This was in analogy with earlier findings with 3'-azido-2',3'-dideoxythymidine 5'-triphosphate. Among the tested pyrophosphate analogs only phosphonoformate was inhibitory.
嗜肝DNA病毒的DNA聚合酶在病毒复制过程中具有两种不同功能。它既作为RNA依赖的DNA聚合酶（逆转录酶），又作为DNA依赖的DNA聚合酶。鸭乙型肝炎病毒（DHBV）制剂用于研究所选化合物对这两种酶活性的抑制作用。逆转录酶活性由从感染DHBV的鸭肝脏中分离出的对放线菌素D耐药、对膦甲酸敏感的DNA聚合酶活性来代表。血清中的DHBV用作DNA依赖的DNA聚合酶活性的来源。测定了焦磷酸和核苷三磷酸类似物对这两种酶制剂的抑制作用。3'-氟-2',3'-二脱氧胸苷5'-三磷酸、阿昔洛韦三磷酸、2',3'-二脱氧胸苷5'-三磷酸、2',3'-二脱氧鸟苷5'-三磷酸和2',3'-二脱氧胸苷5'-三磷酸均有明显抑制作用。两种胸苷类似物三磷酸对逆转录酶活性的抑制作用明显低于对DNA依赖的DNA聚合酶活性的抑制作用。这与早期关于3'-叠氮-2',3'-二脱氧胸苷5'-三磷酸的研究结果相似。在所测试的焦磷酸类似物中，只有膦甲酸具有抑制作用。
