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Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV
Open accessPublished version of a preprint
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. Multi-omics profiling of effects of SARS-CoV-2 and SARS-CoV on A549, a lung-derived human cell line, produces a dataset enabling identification of common and virus-specific mechanisms of infection.
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Metadata
- Authors
- 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., Ehmann, R., Wölfel, R., Jores, J., Kuster, B., Protzer, U., Rad, R., Ziebuhr, J., Thiel, V., Scaturro, P., Mann, M., & Pichlmair, A.
- Venue
- Nature
- Published
- 2021-04-12
- Volume
- 594
- Issue
- 7862
- Pages
- 246-252
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W3154372950
- Cited by
- 685
- References
- 86
- FWCI
- 42.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- Licence
- www.springernature.com/gp/researchers/text-and-data-mining (tdm)
- www.springernature.com/gp/researchers/text-and-data-mining (vor)
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- 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
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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