The inhibitor of cyclin-dependent kinases, olomoucine II, exhibits potent antiviral properties
The inhibitor of cyclin-dependent kinases, olomoucine II, exhibits potent antiviral properties
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DOI：
10.3851/imp1460
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发表时间：
2010-01-01
影响因子：
--
通讯作者：
Vojtesek, Borivoj
中科院分区：
文献类型：
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作者：
Holcakova, Jitka;Tomasec, Peter;Vojtesek, Borivoj
背景：Olomoucine II 是 roscovitine 的最新衍生物，是一种极其有效的细胞周期蛋白依赖性激酶活性药理学抑制剂。在此，我们报告olomoucine II也是一种有效的抗病毒剂。方法：在评估病毒生长和复制的体外测定中测试了olomoucine II对一系列人类病毒的抗病毒活性。结果：Olomoucine II抑制多种野生型人类病毒的复制，包括单纯疱疹病毒、人类4型腺病毒和人类巨细胞病毒。 Olomoucine II 还抑制对传统阿昔洛韦治疗耐药的痘苗病毒和单纯疱疹病毒突变体的复制。该报告首次证明痘病毒对细胞周期蛋白依赖性激酶抑制剂敏感。奥洛穆辛 II 的抗病毒作用可以在比罗可维汀更低的浓度下观察到，尽管两者都是短期的。一个值得注意的观察结果是，奥洛穆辛 II 与 DNA 聚合酶抑制剂西多福韦联合使用时，能够几乎完全消除受感染细胞中传染性 4 型腺病毒子代的传播。结论：我们的结果表明，当针对两种互补的抗病毒机制时，可以观察到强烈的累加效应。
Background: Olomoucine II, the most recent derivative of roscovitine, is an exceptionally potent pharmacological inhibitor of cyclin-dependent kinase activities. Here, we report that olomoucine II is also an effective antiviral agent.Methods: Antiviral activities of olomoucine II were tested on a range of human viruses in in vitro assays that evaluated viral growth and replication.Results: Olomoucine II inhibited replication of a broad range of wild-type human viruses, including herpes simplex virus, human adenovirus type-4 and human cytomegalovirus. Olomoucine II also inhibited replication of vaccinia virus and herpes simplex virus mutants resistant to conventional acyclovir treatment. This report is the first demonstration of a poxvirus being sensitive to a cyclin-dependent kinase inhibitor. The antiviral effects of olomoucine II could be observed at lower concentrations than with roscovitine, although both were short-term. A remarkable observation was that olomoucine II, when used in combination with the DNA polymerase inhibitor cidofovir, was able to almost completely eliminate the spread of infectious adenovirus type-4 progeny from infected cells.Conclusions: Our results show that when targeting two complementary antiviral mechanisms, strongly additive effects could be observed.