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

Authors :
Holcakova J
Tomasec P
Bugert JJ
Wang EC
Wilkinson GW
Hrstka R
Krystof V
Strnad M
Vojtesek B
Source :
Antiviral chemistry & chemotherapy [Antivir Chem Chemother] 2010 Jan 05; Vol. 20 (3), pp. 133-42. Date of Electronic Publication: 2010 Jan 05.
Publication Year :
2010

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.<br />Methods: Antiviral activities of olomoucine II were tested on a range of human viruses in in vitro assays that evaluated viral growth and replication.<br />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.<br />Conclusions: Our results show that when targeting two complementary antiviral mechanisms, strongly additive effects could be observed.

Details

Language :
English
ISSN :
2040-2066
Volume :
20
Issue :
3
Database :
MEDLINE
Journal :
Antiviral chemistry & chemotherapy
Publication Type :
Academic Journal
Accession number :
20054100
Full Text :
https://doi.org/10.3851/IMP1460