2. Academic Validation
  3. Tyrphostin AG1478 Inhibits Encephalomyocarditis Virus and Hepatitis C Virus by Targeting Phosphatidylinositol 4-Kinase IIIα

Tyrphostin AG1478 Inhibits Encephalomyocarditis Virus and Hepatitis C Virus by Targeting Phosphatidylinositol 4-Kinase IIIα

  • Antimicrob Agents Chemother. 2016 Sep 23;60(10):6402-6. doi: 10.1128/AAC.01331-16.
Cristina M Dorobantu 1,  Christian Harak 2,  Rahel Klein 2,  Lonneke van der Linden 3,  Jeroen R P M Strating 1,  Hilde M van der Schaar 1,  Volker Lohmann 2,  Frank J M van Kuppeveld 4
Affiliations

Affiliations

  • 1 Department of Infectious Diseases & Immunology, Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
  • 2 Department of Infectious Diseases, Molecular Virology, University of Heidelberg, Heidelberg, Germany.
  • 3 Department of Medical Microbiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, University of Leuven, Leuven, Belgium.
  • 4 Department of Infectious Diseases & Immunology, Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands f.j.m.vankuppeveld@uu.nl.
PMID: 27480860 DOI: 10.1128/AAC.01331-16
Abstract

Encephalomyocarditis virus (EMCV), like hepatitis C virus (HCV), requires phosphatidylinositol 4-kinase IIIα (PI4KA) for genome replication. Here, we demonstrate that tyrphostin AG1478, a known epidermal growth factor receptor (EGFR) inhibitor, also inhibits PI4KA activity, both in vitro and in cells. AG1478 impaired replication of EMCV and HCV but not that of an EMCV mutant previously shown to escape PI4KA inhibition. This work uncovers novel cellular and Antiviral properties of AG1478, a compound previously regarded only as a Cancer chemotherapy agent.

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