The inhibitor of cyclin-dependent kinases, olomoucine II, exhibits potent antiviral properties

细胞周期蛋白依赖性激酶抑制剂 olomoucine II 具有强效的抗病毒特性

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作者:Jitka Holcakova, Peter Tomasec, Joachim J Bugert, Eddie Cy Wang, Gavin Wg Wilkinson, Roman Hrstka, Vladimir Krystof, Miroslav Strnad, Borivoj Vojtesek

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.

Conclusions

Our results show that when targeting two complementary antiviral mechanisms, strongly additive effects could be observed.

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.

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