The inhibitor of cyclin-dependent kinases, olomoucine II, exhibits potent antiviral properties.
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.
Holcakova
Jitka
J
Department of Oncological and Experimental Pathology, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
Tomasec
Peter
P
Bugert
Joachim J
JJ
Wang
Eddie Cy
EC
Wilkinson
Gavin Wg
GW
Hrstka
Roman
R
Krystof
Vladimir
V
Strnad
Miroslav
M
Vojtesek
Borivoj
B
D000998:Antiviral Agents / Q000494:pharmacology*; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D006801:Humans; D020128:Inhibitory Concentration 50; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology*; D018406:Virus Physiological Phenomena / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects; D014780:Viruses / Q000201:enzymology* / Q000254:growth & development
D000998:Antiviral Agents; D047428:Protein Kinase Inhibitors; D011687:Purines; C475587:olomoucine II; D018844:Cyclin-Dependent Kinases