Tyrphostin AG1478 inhibits encephalomyocarditis virus and hepatitis C virus by targeting phosphatidylinositol 4-kinase IIIα

Cristina M Dorobantu; Christian Harak; Rahel Klein; Lonneke van der Linden; Jeroen R P M Strating; Hilde M van der Schaar; Volker Lohmann; Frank J M van Kuppeveld

doi:10.1128/AAC.01331-16

Tyrphostin AG1478 inhibits encephalomyocarditis virus and hepatitis C virus by targeting phosphatidylinositol 4-kinase IIIα

Cristina M Dorobantu, Christian Harak, Rahel Klein, Lonneke van der Linden, Jeroen R P M Strating, Hilde M van der Schaar, Volker Lohmann, Frank J M van Kuppeveld

Research output: Contribution to journal › Article › Academic › peer-review

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 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 only regarded as cancer chemotherapy agent.

Original language	English
Pages (from-to)	6402-6406
Journal	Antimicrobial Agents and Chemotherapy
Volume	60
Issue number	10
DOIs	https://doi.org/10.1128/AAC.01331-16
Publication status	Published - Sept 2016

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Dorobantu, C. M., Harak, C., Klein, R., van der Linden, L., Strating, J. R. P. M., van der Schaar, H. M., Lohmann, V., & van Kuppeveld, F. J. M. (2016). Tyrphostin AG1478 inhibits encephalomyocarditis virus and hepatitis C virus by targeting phosphatidylinositol 4-kinase IIIα. Antimicrobial Agents and Chemotherapy, 60(10), 6402-6406. https://doi.org/10.1128/AAC.01331-16

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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 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 only regarded as cancer chemotherapy agent.",

author = "Dorobantu, {Cristina M} and Christian Harak and Rahel Klein and {van der Linden}, Lonneke and Strating, {Jeroen R P M} and {van der Schaar}, {Hilde M} and Volker Lohmann and {van Kuppeveld}, {Frank J M}",

year = "2016",

month = sep,

doi = "10.1128/AAC.01331-16",

language = "English",

volume = "60",

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AU - Dorobantu, Cristina M

AU - Harak, Christian

AU - Klein, Rahel

AU - van der Linden, Lonneke

AU - Strating, Jeroen R P M

AU - van der Schaar, Hilde M

AU - Lohmann, Volker

AU - van Kuppeveld, Frank J M

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AB - 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 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 only regarded as cancer chemotherapy agent.

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DO - 10.1128/AAC.01331-16

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SN - 0066-4804

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JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

IS - 10

ER -

Tyrphostin AG1478 inhibits encephalomyocarditis virus and hepatitis C virus by targeting phosphatidylinositol 4-kinase IIIα

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