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.
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: P Ljungman; P Ribaud; M Eyrich; S Matthes-Martin; H Einsele; M Bleakley; M Machaczka; M Bierings; A Bosi; N Gratecos; C Cordonnier Journal: Bone Marrow Transplant Date: 2003-03 Impact factor: 5.483
Authors: Susan C Jacobs; Andrew J Davison; Sharon Carr; Alice M Bennett; Robert Phillpotts; Gavin W G Wilkinson Journal: J Gen Virol Date: 2004-11 Impact factor: 3.891
Authors: Robert C Reynolds; Subramaniam Ananthan; Ellen Faaleolea; Judith V Hobrath; Cecil D Kwong; Clinton Maddox; Lynn Rasmussen; Melinda I Sosa; Elizabeth Thammasuvimol; E Lucile White; Wei Zhang; John A Secrist Journal: Tuberculosis (Edinb) Date: 2011-06-25 Impact factor: 3.131
Authors: Mackenzie J Dodge; Katelyn M MacNeil; Tanner M Tessier; Jason B Weinberg; Joe S Mymryk Journal: Antiviral Res Date: 2021-02-10 Impact factor: 5.970
Authors: Jitka Holcakova; Petr Muller; Peter Tomasec; Roman Hrstka; Marta Nekulova; Vladimir Krystof; Miroslav Strnad; Gavin W G Wilkinson; Borivoj Vojtesek Journal: PLoS One Date: 2014-02-21 Impact factor: 3.240