Journalartikel
Autorenliste: 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; Woelfel, Roman; Jores, Joerg; Kuster, Bernhard; Protzer, Ulrike; Rad, Roland; Ziebuhr, John; Thiel, Volker; Scaturro, Pietro; Mann, Matthias; Pichlmair, Andreas
Jahr der Veröffentlichung: 2021
Seiten: 246-24+
Zeitschrift: Nature
Bandnummer: 594
Heftnummer: 7862
ISSN: 0028-0836
eISSN: 1476-4687
Open Access Status: Hybrid
DOI Link: https://doi.org/10.1038/s41586-021-03493-4
Verlag: Nature Research
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 pathophysiology(1-10). 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-beta 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 ) 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.
Zitierstile
Harvard-Zitierstil: Stukalov, A., Girault, V., Grass, V., Karayel, O., Bergant, V., Urban, C., et al. (2021) Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV, Nature, 594(7862), pp. 246-24+. https://doi.org/10.1038/s41586-021-03493-4
APA-Zitierstil: Stukalov, A., Girault, V., Grass, V., Karayel, O., Bergant, V., Urban, C., Haas, D., Huang, Y., Oubraham, L., Wang, A., Hamad, M., Piras, A., Hansen, F., Tanzer, M., Paron, I., Zinzula, L., Engleitner, T., Reinecke, M., Lavacca, T., ...Pichlmair, A. (2021). Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature. 594(7862), 246-24+. https://doi.org/10.1038/s41586-021-03493-4
Schlagwörter
COMPUTATIONAL PLATFORM; DIMERIZATION DOMAIN; MMP-9; Vimentin
