2. Academic Validation
  3. JNK kinase regulates phosphorylation of HCoV-229E nucleocapsid protein

JNK kinase regulates phosphorylation of HCoV-229E nucleocapsid protein

  • Npj Viruses. 2025 Sep 18;3(1):69. doi: 10.1038/s44298-025-00152-7.
Yannick Brüggemann 1,  Toni Luise Meister 2 3 4 5,  Natalie Heinen 2,  Emely Richter 2,  Saskia Westhoven 2 6,  Michael Poppe 7,  Mohammed Samer Shaban 7,  Leyla Sirkinti 2 8,  Maximilian Nocke 2 8,  Daniel Todt 2 8 9,  Stephanie Pfaender 2 6 10,  Michael Kracht 7,  Eike Steinmann 11 12
Affiliations

Affiliations

  • 1 Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany. yannick.brueggemann@ruhr-uni-bochum.de.
  • 2 Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany.
  • 3 Institute for Infection Research and Vaccine Development (IIRVD), Centre for Internal Medicine, University Medical Centre Hamburg-Eppendorf (UKE), Hamburg, Germany.
  • 4 Department for Clinical Immunology of Infectious Diseases, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
  • 5 German Centre for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany.
  • 6 Research Unit Emerging Viruses, Leibniz Institute of Virology (LIV), Hamburg, Germany.
  • 7 Rudolf Buchheim Institute of Pharmacology, Justus Liebig University, Giessen, Germany.
  • 8 Department of Translational and Computational Infection Research, Ruhr University Bochum, Bochum, Germany.
  • 9 European Virus Bioinformatics Center (EVBC), Jena, Germany.
  • 10 University of Lübeck, Institute of Virology and Cell Biology, Lübeck, Germany.
  • 11 Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany. eike.steinmann@ruhr-uni-bochum.de.
  • 12 German Centre for Infection Research (DZIF), External Partner Site, Bochum, Germany. eike.steinmann@ruhr-uni-bochum.de.
PMID: 40968155 DOI: 10.1038/s44298-025-00152-7
Abstract

Identifying common host factors essential for the replication cycles of human coronaviruses (HCoV) could help uncover potential therapeutic targets. Mitogen-activated protein kinases (MAPKs) regulate critical cellular signaling pathways. Among them, c-Jun N-terminal kinases (JNK) are activated in response to diverse environmental stresses, including viral infections. However, the relevance of the JNK pathway for host responses and replication of HCoV infections has remained elusive. Using live-cell microscopy, quantitative immunofluorescence and immunoblotting, we found that JNK is specifically activated in cells infected with HCoV-229E and plays a crucial role in mediating the phosphorylation of the viral nucleocapsid (N) protein, an essential step required during the viral replication cycle. Consequently, pharmacological inhibition of JNK kinase activity impeded HCoV-229E as well as SARS-CoV-2 Infection. Given the conservation of phosphorylation sites within the nucleocapsid protein across coronaviruses, inhibitors targeting these N protein kinases, such as JNK, may hold therapeutic promise as broad-spectrum CoV antivirals.

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