Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. / Stukalov, Alexey; Girault, Virginie; Grass, Vincent; Karayel, Ozge; Bergant, Valter; Urban, Christian; Haas, Darya A; Huang, Yiqi; Oubraham, Lila; Wang, Anqi; Hamad, M Sabri; Piras, Antonio; Hansen, Fynn M; Tanzer, Maria C; Paron, Igor; Zinzula, Luca; Engleitner, Thomas; Reinecke, Maria; Lavacca, Teresa M; Ehmann, Rosina; Wölfel, Roman; Jores, Jörg; Kuster, Bernhard; Protzer, Ulrike; Rad, Roland; Ziebuhr, John; Thiel, Volker; Scaturro, Pietro; Mann, Matthias; Pichlmair, Andreas.

In: Nature, 12.04.2021.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Stukalov, A, Girault, V, Grass, V, Karayel, O, Bergant, V, Urban, C, Haas, DA, Huang, Y, Oubraham, L, Wang, A, Hamad, MS, Piras, A, Hansen, FM, Tanzer, MC, Paron, I, Zinzula, L, Engleitner, T, Reinecke, M, Lavacca, TM, Ehmann, R, Wölfel, R, Jores, J, Kuster, B, Protzer, U, Rad, R, Ziebuhr, J, Thiel, V, Scaturro, P, Mann, M & Pichlmair, A 2021, 'Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV', Nature. https://doi.org/10.1038/s41586-021-03493-4

APA

Stukalov, A., Girault, V., Grass, V., Karayel, O., Bergant, V., Urban, C., Haas, D. A., Huang, Y., Oubraham, L., Wang, A., Hamad, M. S., Piras, A., Hansen, F. M., Tanzer, M. C., Paron, I., Zinzula, L., Engleitner, T., Reinecke, M., Lavacca, T. M., ... Pichlmair, A. (2021). Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature. https://doi.org/10.1038/s41586-021-03493-4

Vancouver

Stukalov A, Girault V, Grass V, Karayel O, Bergant V, Urban C et al. Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature. 2021 Apr 12. https://doi.org/10.1038/s41586-021-03493-4

Author

Stukalov, Alexey ; Girault, Virginie ; Grass, Vincent ; Karayel, Ozge ; Bergant, Valter ; Urban, Christian ; Haas, Darya A ; Huang, Yiqi ; Oubraham, Lila ; Wang, Anqi ; Hamad, M Sabri ; Piras, Antonio ; Hansen, Fynn M ; Tanzer, Maria C ; Paron, Igor ; Zinzula, Luca ; Engleitner, Thomas ; Reinecke, Maria ; Lavacca, Teresa M ; Ehmann, Rosina ; Wölfel, Roman ; Jores, Jörg ; Kuster, Bernhard ; Protzer, Ulrike ; Rad, Roland ; Ziebuhr, John ; Thiel, Volker ; Scaturro, Pietro ; Mann, Matthias ; Pichlmair, Andreas. / Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. In: Nature. 2021.

Bibtex

@article{145bbdc0da154c319801d2bcd984abbd,
title = "Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV",
abstract = "The emergence and global spread of SARS-CoV-2 has resulted in the urgent need for an in-depth understanding of molecular functions of viral proteins and their interactions with the host proteome. Several individual omics studies have extended our knowledge of COVID-19 pathophysiology1-10. Integration of such datasets to obtain a holistic view of virus-host interactions and to define the pathogenic properties of SARS-CoV-2 is limited by the heterogeneity of the experimental systems. Here we report a concurrent multi-omics study of SARS-CoV-2 and SARS-CoV. Using state-of-the-art proteomics, we profiled the interactomes of both viruses, as well as their influence on the transcriptome, proteome, ubiquitinome and phosphoproteome of a lung-derived human cell line. Projecting these data onto the global network of cellular interactions revealed crosstalk between the perturbations taking place upon infection with SARS-CoV-2 and SARS-CoV at different levels and enabled identification of distinct and common molecular mechanisms of these closely related coronaviruses. The TGF-β pathway, known for its involvement in tissue fibrosis, was specifically dysregulated by SARS-CoV-2 ORF8 and autophagy was specifically dysregulated by SARS-CoV-2 ORF3. The extensive dataset (available at https://covinet.innatelab.org ) highlights many hotspots that could be targeted by existing drugs and may be used to guide rational design of virus- and host-directed therapies, which we exemplify by identifying inhibitors of kinases and matrix metalloproteases with potent antiviral effects against SARS-CoV-2.",
author = "Alexey Stukalov and Virginie Girault and Vincent Grass and Ozge Karayel and Valter Bergant and Christian Urban and Haas, {Darya A} and Yiqi Huang and Lila Oubraham and Anqi Wang and Hamad, {M Sabri} and Antonio Piras and Hansen, {Fynn M} and Tanzer, {Maria C} and Igor Paron and Luca Zinzula and Thomas Engleitner and Maria Reinecke and Lavacca, {Teresa M} and Rosina Ehmann and Roman W{\"o}lfel and J{\"o}rg Jores and Bernhard Kuster and Ulrike Protzer and Roland Rad and John Ziebuhr and Volker Thiel and Pietro Scaturro and Matthias Mann and Andreas Pichlmair",
year = "2021",
month = apr,
day = "12",
doi = "10.1038/s41586-021-03493-4",
language = "English",
journal = "Nature",
issn = "0028-0836",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV

AU - Stukalov, Alexey

AU - Girault, Virginie

AU - Grass, Vincent

AU - Karayel, Ozge

AU - Bergant, Valter

AU - Urban, Christian

AU - Haas, Darya A

AU - Huang, Yiqi

AU - Oubraham, Lila

AU - Wang, Anqi

AU - Hamad, M Sabri

AU - Piras, Antonio

AU - Hansen, Fynn M

AU - Tanzer, Maria C

AU - Paron, Igor

AU - Zinzula, Luca

AU - Engleitner, Thomas

AU - Reinecke, Maria

AU - Lavacca, Teresa M

AU - Ehmann, Rosina

AU - Wölfel, Roman

AU - Jores, Jörg

AU - Kuster, Bernhard

AU - Protzer, Ulrike

AU - Rad, Roland

AU - Ziebuhr, John

AU - Thiel, Volker

AU - Scaturro, Pietro

AU - Mann, Matthias

AU - Pichlmair, Andreas

PY - 2021/4/12

Y1 - 2021/4/12

N2 - The emergence and global spread of SARS-CoV-2 has resulted in the urgent need for an in-depth understanding of molecular functions of viral proteins and their interactions with the host proteome. Several individual omics studies have extended our knowledge of COVID-19 pathophysiology1-10. Integration of such datasets to obtain a holistic view of virus-host interactions and to define the pathogenic properties of SARS-CoV-2 is limited by the heterogeneity of the experimental systems. Here we report a concurrent multi-omics study of SARS-CoV-2 and SARS-CoV. Using state-of-the-art proteomics, we profiled the interactomes of both viruses, as well as their influence on the transcriptome, proteome, ubiquitinome and phosphoproteome of a lung-derived human cell line. Projecting these data onto the global network of cellular interactions revealed crosstalk between the perturbations taking place upon infection with SARS-CoV-2 and SARS-CoV at different levels and enabled identification of distinct and common molecular mechanisms of these closely related coronaviruses. The TGF-β pathway, known for its involvement in tissue fibrosis, was specifically dysregulated by SARS-CoV-2 ORF8 and autophagy was specifically dysregulated by SARS-CoV-2 ORF3. The extensive dataset (available at https://covinet.innatelab.org ) highlights many hotspots that could be targeted by existing drugs and may be used to guide rational design of virus- and host-directed therapies, which we exemplify by identifying inhibitors of kinases and matrix metalloproteases with potent antiviral effects against SARS-CoV-2.

AB - The emergence and global spread of SARS-CoV-2 has resulted in the urgent need for an in-depth understanding of molecular functions of viral proteins and their interactions with the host proteome. Several individual omics studies have extended our knowledge of COVID-19 pathophysiology1-10. Integration of such datasets to obtain a holistic view of virus-host interactions and to define the pathogenic properties of SARS-CoV-2 is limited by the heterogeneity of the experimental systems. Here we report a concurrent multi-omics study of SARS-CoV-2 and SARS-CoV. Using state-of-the-art proteomics, we profiled the interactomes of both viruses, as well as their influence on the transcriptome, proteome, ubiquitinome and phosphoproteome of a lung-derived human cell line. Projecting these data onto the global network of cellular interactions revealed crosstalk between the perturbations taking place upon infection with SARS-CoV-2 and SARS-CoV at different levels and enabled identification of distinct and common molecular mechanisms of these closely related coronaviruses. The TGF-β pathway, known for its involvement in tissue fibrosis, was specifically dysregulated by SARS-CoV-2 ORF8 and autophagy was specifically dysregulated by SARS-CoV-2 ORF3. The extensive dataset (available at https://covinet.innatelab.org ) highlights many hotspots that could be targeted by existing drugs and may be used to guide rational design of virus- and host-directed therapies, which we exemplify by identifying inhibitors of kinases and matrix metalloproteases with potent antiviral effects against SARS-CoV-2.

U2 - 10.1038/s41586-021-03493-4

DO - 10.1038/s41586-021-03493-4

M3 - Journal article

C2 - 33845483

JO - Nature

JF - Nature

SN - 0028-0836

ER -

ID: 261519914