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Multi-level proteomics reveals host-perturbation strategies of SARS-CoV-2 and SARS-CoV

View ORCID ProfileAlexey Stukalov, View ORCID ProfileVirginie Girault, Vincent Grass, Valter Bergant, Ozge Karayel, View ORCID ProfileChristian Urban, View ORCID ProfileDarya A. Haas, Yiqi Huang, Lila Oubraham, Anqi Wang, Sabri M. Hamad, Antonio Piras, Maria Tanzer, Fynn M. Hansen, Thomas Enghleitner, Maria Reinecke, Teresa M. Lavacca, Rosina Ehmann, Roman Wölfel, Jörg Jores, Bernhard Kuster, Ulrike Protzer, Roland Rad, John Ziebuhr, Volker Thiel, Pietro Scaturro, Matthias Mann, View ORCID ProfileAndreas Pichlmair
doi: https://doi.org/10.1101/2020.06.17.156455
Alexey Stukalov
1Technical University of Munich, School of Medicine, Institute of Virology, 81675 Munich, Germany
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Virginie Girault
1Technical University of Munich, School of Medicine, Institute of Virology, 81675 Munich, Germany
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Vincent Grass
1Technical University of Munich, School of Medicine, Institute of Virology, 81675 Munich, Germany
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Valter Bergant
1Technical University of Munich, School of Medicine, Institute of Virology, 81675 Munich, Germany
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Ozge Karayel
2Department of Proteomics and Signal transduction, Max-Planck Institute of Biochemistry, Martinsried/Munich, 82152, Germany
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Christian Urban
1Technical University of Munich, School of Medicine, Institute of Virology, 81675 Munich, Germany
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Darya A. Haas
1Technical University of Munich, School of Medicine, Institute of Virology, 81675 Munich, Germany
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Yiqi Huang
1Technical University of Munich, School of Medicine, Institute of Virology, 81675 Munich, Germany
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Lila Oubraham
1Technical University of Munich, School of Medicine, Institute of Virology, 81675 Munich, Germany
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Anqi Wang
1Technical University of Munich, School of Medicine, Institute of Virology, 81675 Munich, Germany
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Sabri M. Hamad
1Technical University of Munich, School of Medicine, Institute of Virology, 81675 Munich, Germany
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Antonio Piras
1Technical University of Munich, School of Medicine, Institute of Virology, 81675 Munich, Germany
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Maria Tanzer
2Department of Proteomics and Signal transduction, Max-Planck Institute of Biochemistry, Martinsried/Munich, 82152, Germany
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Fynn M. Hansen
2Department of Proteomics and Signal transduction, Max-Planck Institute of Biochemistry, Martinsried/Munich, 82152, Germany
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Thomas Enghleitner
3Institute of Molecular Oncology and Functional Genomics and Department of Medicine II, School of Medicine, Technical University of Munich, 81675 Munich, Germany
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Maria Reinecke
4Chair of Proteomics and Bioanalytics, Technical University of Munich, 85354 Freising, Germany
5German Cancer Consortium (DKTK), Munich partner site and German Cancer Research Center, (DKFZ) Heidelberg, Germany
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Teresa M. Lavacca
1Technical University of Munich, School of Medicine, Institute of Virology, 81675 Munich, Germany
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Rosina Ehmann
6Bundeswehr Institute of Microbiology, 80937 Munich, Germany
7German Center for Infection Research (DZIF), Munich partner site, Germany
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Roman Wölfel
6Bundeswehr Institute of Microbiology, 80937 Munich, Germany
7German Center for Infection Research (DZIF), Munich partner site, Germany
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Jörg Jores
8Institute of Veterinary Bacteriology, Department of Infectious Diseases and Pathobiology, University of Bern, Bern, Switzerland
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Bernhard Kuster
4Chair of Proteomics and Bioanalytics, Technical University of Munich, 85354 Freising, Germany
5German Cancer Consortium (DKTK), Munich partner site and German Cancer Research Center, (DKFZ) Heidelberg, Germany
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Ulrike Protzer
1Technical University of Munich, School of Medicine, Institute of Virology, 81675 Munich, Germany
7German Center for Infection Research (DZIF), Munich partner site, Germany
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Roland Rad
3Institute of Molecular Oncology and Functional Genomics and Department of Medicine II, School of Medicine, Technical University of Munich, 81675 Munich, Germany
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John Ziebuhr
9Justus Liebig University Giessen, Institute of Medical Virology, 35392 Giessen, Germany
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Volker Thiel
10Institute of Virology and Immunology (IVI), Bern, Switzerland & Department of Infectious Diseases and Pathobiology, University of Bern, Bern, Switzerland
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Pietro Scaturro
1Technical University of Munich, School of Medicine, Institute of Virology, 81675 Munich, Germany
11Systems Arbovirology, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany
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Matthias Mann
2Department of Proteomics and Signal transduction, Max-Planck Institute of Biochemistry, Martinsried/Munich, 82152, Germany
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Andreas Pichlmair
1Technical University of Munich, School of Medicine, Institute of Virology, 81675 Munich, Germany
7German Center for Infection Research (DZIF), Munich partner site, Germany
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  • For correspondence: andreas.pichlmair@tum.de
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Abstract

The sudden global emergence of SARS-CoV-2 urgently requires an in-depth understanding of molecular functions of viral proteins and their interactions with the host proteome. Several omics studies have extended our knowledge of COVID-19 pathophysiology, including some focused on proteomic aspects1–3. To understand how SARS-CoV-2 and related coronaviruses manipulate the host we here characterized interactome, proteome and signaling processes in a systems-wide manner. This identified connections between the corresponding cellular events, revealed functional effects of the individual viral proteins and put these findings into the context of host signaling pathways. We investigated the closely related SARS-CoV-2 and SARS-CoV viruses as well as the influence of SARS-CoV-2 on transcriptome, proteome, ubiquitinome and phosphoproteome of a lung-derived human cell line. Projecting these data onto the global network of cellular interactions revealed relationships between the perturbations taking place upon SARS-CoV-2 infection at different layers and identified unique and common molecular mechanisms of SARS coronaviruses. The results highlight the functionality of individual proteins as well as vulnerability hotspots of SARS-CoV-2, which we targeted with clinically approved drugs. We exemplify this by identification of kinase inhibitors as well as MMPase inhibitors with significant antiviral effects against SARS-CoV-2.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted June 17, 2020.
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Multi-level proteomics reveals host-perturbation strategies of SARS-CoV-2 and SARS-CoV
Alexey Stukalov, Virginie Girault, Vincent Grass, Valter Bergant, Ozge Karayel, Christian Urban, Darya A. Haas, Yiqi Huang, Lila Oubraham, Anqi Wang, Sabri M. Hamad, Antonio Piras, Maria Tanzer, Fynn M. Hansen, Thomas Enghleitner, Maria Reinecke, Teresa M. Lavacca, Rosina Ehmann, Roman Wölfel, Jörg Jores, Bernhard Kuster, Ulrike Protzer, Roland Rad, John Ziebuhr, Volker Thiel, Pietro Scaturro, Matthias Mann, Andreas Pichlmair
bioRxiv 2020.06.17.156455; doi: https://doi.org/10.1101/2020.06.17.156455
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Multi-level proteomics reveals host-perturbation strategies of SARS-CoV-2 and SARS-CoV
Alexey Stukalov, Virginie Girault, Vincent Grass, Valter Bergant, Ozge Karayel, Christian Urban, Darya A. Haas, Yiqi Huang, Lila Oubraham, Anqi Wang, Sabri M. Hamad, Antonio Piras, Maria Tanzer, Fynn M. Hansen, Thomas Enghleitner, Maria Reinecke, Teresa M. Lavacca, Rosina Ehmann, Roman Wölfel, Jörg Jores, Bernhard Kuster, Ulrike Protzer, Roland Rad, John Ziebuhr, Volker Thiel, Pietro Scaturro, Matthias Mann, Andreas Pichlmair
bioRxiv 2020.06.17.156455; doi: https://doi.org/10.1101/2020.06.17.156455

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