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无环鸟苷(acyclovir)是核苷类似物,具有高度选择性抑制单纯疱疹病毒(HSV)复制的作用。无环鸟苷进入HSV感染细胞后迅速被HSV特异的胸腺核苷激酶磷酸化形成一磷酸无环鸟苷,此后由细胞胸腺核苷激酶和其它细胞酶体系完成其余磷酸化过程形成三磷酸无环鸟苷,后者抑制HSV-DNA聚合酶,导致病毒DNA链失活。抑制HSV-DNA聚合酶所需三磷酸无环鸟苷的浓度比抑制宿主细胞DNA聚合酶所需浓度低得多;加上无环鸟苷与病毒胸腺核苷激酶的亲合力又比其与细胞胸腺核苷激酶的亲合力高200倍(因此,非HSV感染细胞中查不到已磷酸化的无环鸟苷),此即无环鸟苷的特异性。已发现该药作用于水痘带状疱疹病毒(VZV)时,具有类似机理。
Acyclovir is a nucleoside analog that has a highly selective inhibitory effect on herpes simplex virus (HSV) replication. Acycline guanosine enters HSV infected cells and is rapidly phosphorylated by HSV-specific thymidine kinase to form acyclo- guanosine monophosphate. Afterwards, the other phosphorylation processes are completed by the cellular thymidine kinase and other cellular enzyme systems to form an acyclic triphosphate Guanosine, which inhibits HSV-DNA polymerase, leads to inactivation of the viral DNA strands. The concentration of acyclovir triphosphate required to inhibit HSV-DNA polymerase is much lower than that required to inhibit DNA polymerase in the host cell; and the affinity of acyclovir to the virus thymidine kinase is less than that of the cell The affinity of thymidine kinase is 200-fold higher (therefore, no phosphorylated acyclovir can be found in non-HSV infected cells), which is acyclovir specificity. It has been found that this drug has a similar mechanism of action when used against Varicella Zoster virus (VZV).