Loading...
The novel immunosuppressive protein kinase C inhibitor sotrastaurin has no pro-viral effects on the replication cycle of hepatitis B or C virus.
von Hahn, Thomas Schulze, Andreas Chicano Wust, Ivan Heidrich, Benjamin Becker, Thomas Steinmann, Eike Helfritz, Fabian A Rohrmann, Katrin Urban, Stephan Manns, Michael P
von Hahn, Thomas
Schulze, Andreas
Chicano Wust, Ivan
Heidrich, Benjamin
Becker, Thomas
Steinmann, Eike
Helfritz, Fabian A
Rohrmann, Katrin
Urban, Stephan
Manns, Michael P
Files
Loading...
open access publication
Adobe PDF, 685.35 KB
Other Titles
Abstract
The pan-protein kinase C (PKC) inhibitor sotrastaurin (AEB071) is a novel immunosuppressant currently in phase II trials for immunosuppression after solid organ transplantation. Besides T-cell activation, PKC affects numerous cellular processes that are potentially important for the replication of hepatitis B virus (HBV) and hepatitis C virus (HCV), major blood-borne pathogens prevalent in solid organ transplant recipients. This study uses state of the art virological assays to assess the direct, non-immune mediated effects of sotrastaurin on HBV and HCV. Most importantly, sotrastaurin had no pro-viral effect on either HBV or HCV. In the presence of high concentrations of sotrastaurin, well above those used clinically and close to levels where cytotoxic effects become detectable, there was a reduction of HCV and HBV replication. This reduction is very likely due to cytotoxic and/or anti-proliferative effects rather than direct anti-viral activity of the drug. Replication cycle stages other than genome replication such as viral cell entry and spread of HCV infection directly between adjacent cells was clearly unaffected by sotrastaurin. These data support the evaluation of sotrastaurin in HBV and/or HCV infected transplant recipients.
Citation
The novel immunosuppressive protein kinase C inhibitor sotrastaurin has no pro-viral effects on the replication cycle of hepatitis B or C virus. 2011, 6 (9):e24142 PLoS ONE
Publisher
Journal
PubMed ID
PubMed Central ID
Additional Links
Embedded video
Type
Article
Language
en
Description
Series/Report no.
ISSN
1932-6203