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

Antiviral chemistry & chemotherapy 2010 Jan 1; 20(3):133-42

Link to PubMed abstract

Holcakova J, Tomasec P, Bugert J JJ, Wang E EC, Wilkinson G GW, Hrstka R, Krystof V, Strnad M, Vojtesek B

Department of Oncological and Experimental Pathology, Masaryk Memorial Cancer Institute, Brno, Czech Republic.

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.

Keywords: cyclin-dependent kinase antiviral