2. Academic Validation
  3. Multiple cyclophilins involved in different cellular pathways mediate HCV replication

Multiple cyclophilins involved in different cellular pathways mediate HCV replication

  • Virology. 2010 Feb 5;397(1):43-55. doi: 10.1016/j.virol.2009.10.043.
L Alex Gaither 1,  Jason Borawski,  Leah J Anderson,  Kara A Balabanis,  Piroska Devay,  Gerard Joberty,  Christina Rau,  Markus Schirle,  Tewis Bouwmeester,  Craig Mickanin,  Shanchuan Zhao,  Chad Vickers,  Lac Lee,  Gejing Deng,  Jeremy Baryza,  Roger A Fujimoto,  Kai Lin,  Teresa Compton,  Brigitte Wiedmann
Affiliations

Affiliation

  • 1 Novartis Institutes of Biomedical Research, Cambridge, MA 02139, USA.
PMID: 19932913 DOI: 10.1016/j.virol.2009.10.043
Abstract

Three Cyclophilin inhibitors (DEBIO-025, SCY635, and NIM811) are currently in clinical trials for hepatitis C therapy. The mechanism of action of these, however, is not completely understood. There are at least 16 cyclophilins expressed in human cells which are involved in a diverse set of cellular processes. Large-scale siRNA experiments, chemoproteomic assays with Cyclophilin binding compounds, and mRNA profiling of HCV replicon containing cells were used to identify the cyclophilins that are instrumental to HCV replication. The previously reported Cyclophilin A was confirmed and additional Cyclophilin containing pathways were identified. Together, the experiments provide strong evidence that NIM811 reduces viral replication by inhibition of multiple cyclophilins and pathways with protein trafficking as the most strongly and persistently affected pathway.

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