（RS）-9-[4-羟基-2-（羟甲基）丁基]鸟嘌呤对水痘-带状疱疹病毒在细胞培养中复制的抑制作用
Inhibiting effect of (RS)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine on varicella-zoster virus replication in cell culture.
作者信息
Abele G, Karlström A, Harmenberg J, Shigeta S, Larsson A, Lindborg B, Wahren B
出版信息
Antimicrob Agents Chemother. 1987 Jan;31(1):76-80. doi: 10.1128/AAC.31.1.76.
Abstract
The activity and mode of action of the new nucleoside analog (RS)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine (2HM-HBG) against varicella-zoster virus (VZV) were determined. In cell culture, replication of different strains of VZV was inhibited to 50% by 0.4 to 0.7 microM 2HM-HBG, while 685 microM was required to inhibit 50% of the DNA synthesis in uninfected human lung fibroblasts. A thymidine kinase-negative VZV strain was not inhibited by 100 microM 2HM-HBG. Inhibition of VZV replication was not reversible after 7 to 14 days of incubation, depending on the multiplicity of VZV. 2HM-HBG was shown to be selectively phosphorylated by purified VZV thymidine kinase, with an inhibition constant of 32.5 microM. The antiviral activity of 2HM-HBG in cell culture was decreased by the addition of deoxythymidine and deoxycytidine but not by other ribo- or deoxyribonucleosides.
摘要
测定了新型核苷类似物（RS）-9-[4-羟基-2-（羟甲基）丁基]鸟嘌呤（2HM-HBG）对水痘带状疱疹病毒（VZV）的活性及作用方式。在细胞培养中，0.4至0.7微摩尔的2HM-HBG可将不同株VZV的复制抑制50%，而抑制未感染人肺成纤维细胞中50%的DNA合成则需要685微摩尔。100微摩尔的2HM-HBG对胸苷激酶阴性的VZV株无抑制作用。根据VZV的感染复数，孵育7至14天后，VZV复制的抑制作用不可逆。纯化的VZV胸苷激酶可使2HM-HBG选择性磷酸化，其抑制常数为32.5微摩尔。添加脱氧胸苷和脱氧胞苷会降低2HM-HBG在细胞培养中的抗病毒活性，但其他核糖核苷或脱氧核糖核苷则不会。
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