title: 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.
authors.affiliation: Department of Oncological and Experimental Pathology, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
authors.forename: Jitka
authors.initials: J
authors.lastname: Holcakova
authors.forename: Peter
authors.initials: P
authors.lastname: Tomasec
authors.forename: Joachim J
authors.initials: JJ
authors.lastname: Bugert
authors.forename: Eddie Cy
authors.initials: EC
authors.lastname: Wang
authors.forename: Gavin Wg
authors.initials: GW
authors.lastname: Wilkinson
authors.forename: Roman
authors.initials: R
authors.lastname: Hrstka
authors.forename: Vladimir
authors.initials: V
authors.lastname: Krystof
authors.forename: Miroslav
authors.initials: M
authors.lastname: Strnad
authors.forename: Borivoj
authors.initials: B
authors.lastname: Vojtesek
mesh_terms: 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
chemical_list: D000998:Antiviral Agents; D047428:Protein Kinase Inhibitors; D011687:Purines; C475587:olomoucine II; D018844:Cyclin-Dependent Kinases