Browsing by Subject "Drug-target prediction"

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    Multi-omics characterization of the monkeypox virus infection
    (2024) Huang, Yiqi; Bergant, Valter; Grass, Vincent; Emslander, Quirin; Hamad, M. Sabri; Hubel, Philipp; Mergner, Julia; Piras, Antonio; Krey, Karsten; Henrici, Alexander; Öllinger, Rupert; Tesfamariam, Yonas M.; Dalla Rosa, Ilaria; Bunse, Till; Sutter, Gerd; Ebert, Gregor; Schmidt, Florian I.; Way, Michael; Rad, Roland; Bowie, Andrew G.; Protzer, Ulrike; Pichlmair, Andreas; Huang, Yiqi; Institute of Virology, Technical University of Munich, School of Medicine, Munich, Germany; Bergant, Valter; Institute of Virology, Technical University of Munich, School of Medicine, Munich, Germany; Grass, Vincent; Institute of Virology, Technical University of Munich, School of Medicine, Munich, Germany; Emslander, Quirin; Institute of Virology, Technical University of Munich, School of Medicine, Munich, Germany; Hamad, M. Sabri; Institute of Virology, Technical University of Munich, School of Medicine, Munich, Germany; Hubel, Philipp; Innate Immunity Laboratory, Max-Planck Institute of Biochemistry, Munich, Germany; Mergner, Julia; Bavarian Center for Biomolecular Mass Spectrometry at University Hospital rechts der Isar (BayBioMS@MRI), Technical University of Munich, Munich, Germany; Piras, Antonio; Institute of Virology, Technical University of Munich, School of Medicine, Munich, Germany; Krey, Karsten; Institute of Virology, Technical University of Munich, School of Medicine, Munich, Germany; Henrici, Alexander; Institute of Virology, Technical University of Munich, School of Medicine, Munich, Germany; Öllinger, Rupert; Institute of Molecular Oncology and Functional Genomics and Department of Medicine II, School of Medicine, Technical University of Munich, Munich, Germany; Tesfamariam, Yonas M.; Institute of Innate Immunity, Medical Faculty, University of Bonn, Bonn, Germany; Dalla Rosa, Ilaria; Cellular signalling and cytoskeletal function laboratory, The Francis Crick Institute, 1 Midland Road, NW1 1AT, London, UK; Bunse, Till; Institute of Virology, Technical University of Munich, School of Medicine, Munich, Germany; Sutter, Gerd; Institute for Infectious Diseases and Zoonoses, Department of Veterinary Sciences, LMU Munich, Munich, Germany; Ebert, Gregor; Institute of Virology, Technical University of Munich, School of Medicine/Helmholtz Munich, Munich, Germany; Schmidt, Florian I.; Institute of Innate Immunity, Medical Faculty, University of Bonn, Bonn, Germany; Way, Michael; Cellular signalling and cytoskeletal function laboratory, The Francis Crick Institute, 1 Midland Road, NW1 1AT, London, UK; Rad, Roland; Institute of Molecular Oncology and Functional Genomics and Department of Medicine II, School of Medicine, Technical University of Munich, Munich, Germany; Bowie, Andrew G.; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland; Protzer, Ulrike; German Centre for Infection Research (DZIF), Partner site Munich, Munich, Germany; Pichlmair, Andreas; Institute of Virology, Technical University of Munich, School of Medicine, Munich, Germany
    Multiple omics analyzes of Vaccinia virus (VACV) infection have defined molecular characteristics of poxvirus biology. However, little is known about the monkeypox (mpox) virus (MPXV) in humans, which has a different disease manifestation despite its high sequence similarity to VACV. Here, we perform an in-depth multi-omics analysis of the transcriptome, proteome, and phosphoproteome signatures of MPXV-infected primary human fibroblasts to gain insights into the virus-host interplay. In addition to expected perturbations of immune-related pathways, we uncover regulation of the HIPPO and TGF-β pathways. We identify dynamic phosphorylation of both host and viral proteins, which suggests that MAPKs are key regulators of differential phosphorylation in MPXV-infected cells. Among the viral proteins, we find dynamic phosphorylation of H5 that influenced the binding of H5 to dsDNA. Our extensive dataset highlights signaling events and hotspots perturbed by MPXV, extending the current knowledge on poxviruses. We use integrated pathway analysis and drug-target prediction approaches to identify potential drug targets that affect virus growth. Functionally, we exemplify the utility of this approach by identifying inhibitors of MTOR, CHUK/IKBKB, and splicing factor kinases with potent antiviral efficacy against MPXV and VACV.