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

ABSTRACT: 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.

SUBMITTER: Holcakova J 

PROVIDER: S-EPMC2948526 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature