Nature (London), 2021-06, Vol.594 (7862), p.246-252
- 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
2021
Details
- Autor(en) / Beteiligte
- 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
- Titel
- Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV
- Ist Teil von
- Nature (London), 2021-06, Vol.594 (7862), p.246-252
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2021
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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 . 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0028-0836eISSN: 1476-4687DOI: 10.1038/s41586-021-03493-4Titel-ID: cdi_proquest_journals_2540566362
- Format
- –
- Schlagworte
- Animals, Antiviral agents, Antiviral Agents - pharmacology, Autophagy, Autophagy - drug effects, Cell cycle, Cell Line, Cellular communication, Coronaviruses, COVID-19 - immunology, COVID-19 - metabolism, COVID-19 - virology, Crosstalk, Datasets, Datasets as Topic, DNA damage, Drug development, Drug Evaluation, Preclinical, Fibrosis, Gene expression, Heterogeneity, Host-Pathogen Interactions - immunology, Host-virus relationships, Humans, Infections, Kinases, Lungs, Matrix Metalloproteinase Inhibitors - pharmacology, Metabolism, Molecular modelling, Observations, Perturbation, Phagocytosis, Phosphorylation, Physiological aspects, Protein Interaction Maps, Protein Kinase Inhibitors - pharmacology, Protein Processing, Post-Translational, Proteins, Proteome - chemistry, Proteome - metabolism, Proteomes, Proteomics, SARS-CoV-2 - immunology, SARS-CoV-2 - pathogenicity, Severe acute respiratory syndrome, Severe Acute Respiratory Syndrome - immunology, Severe Acute Respiratory Syndrome - metabolism, Severe Acute Respiratory Syndrome - virology, Severe acute respiratory syndrome coronavirus 2, Severe acute respiratory syndrome-related coronavirus - immunology, Severe acute respiratory syndrome-related coronavirus - pathogenicity, Transcriptomes, Transforming Growth Factor beta - metabolism, Ubiquitination, Viral diseases, Viral infections, Viral Proteins - chemistry, Viral Proteins - metabolism, Viroporin Proteins - metabolism, Viruses