tetano
Editor, Senior Moderator
Nature
. 2021 Apr 12.
doi: 10.1038/s41586-021-03493-4. Online ahead of print.
Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV
Alexey Stukalov[SUP] #[/SUP][SUP] 1 [/SUP], Virginie Girault[SUP] #[/SUP][SUP] 1 [/SUP], Vincent Grass[SUP] #[/SUP][SUP] 1 [/SUP], Ozge Karayel[SUP] #[/SUP][SUP] 2 [/SUP], Valter Bergant[SUP] #[/SUP][SUP] 1 [/SUP], Christian Urban[SUP] #[/SUP][SUP] 1 [/SUP], Darya A Haas[SUP] #[/SUP][SUP] 1 [/SUP], Yiqi Huang[SUP] #[/SUP][SUP] 1 [/SUP], Lila Oubraham[SUP] 1 [/SUP], Anqi Wang[SUP] 1 [/SUP], M Sabri Hamad[SUP] 1 [/SUP], Antonio Piras[SUP] 1 [/SUP], Fynn M Hansen[SUP] 2 [/SUP], Maria C Tanzer[SUP] 2 [/SUP], Igor Paron[SUP] 2 [/SUP], Luca Zinzula[SUP] 3 [/SUP], Thomas Enghleitner[SUP] 4 [/SUP], Maria Reinecke[SUP] 5 6 [/SUP], Teresa M Lavacca[SUP] 1 [/SUP], Rosina Ehmann[SUP] 7 8 [/SUP], Roman W?lfel[SUP] 7 8 [/SUP], J?rg Jores[SUP] 9 [/SUP], Bernhard Kuster[SUP] 5 6 [/SUP], Ulrike Protzer[SUP] 1 8 [/SUP], Roland Rad[SUP] 4 [/SUP], John Ziebuhr[SUP] 10 [/SUP], Volker Thiel[SUP] 11 [/SUP], Pietro Scaturro[SUP] 1 12 [/SUP], Matthias Mann[SUP] 2 [/SUP], Andreas Pichlmair[SUP] 13 14 [/SUP]
Affiliations
Abstract
The 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 individual omics studies have extended our knowledge of COVID-19 pathophysiology[SUP]1-10[/SUP]. 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. We therefore conducted a concurrent multi-omics study of SARS-CoV-2 and SARS-CoV. Using state-of-the-art proteomics, we profiled the interactome of both viruses, as well as their influence on transcriptome, proteome, ubiquitinome and phosphoproteome in a lung-derived human cell line. Projecting these data onto the global network of cellular interactions revealed crosstalk between the perturbations taking place upon SARS-CoV-2 and SARS-CoV infections at different layers and identified unique and common molecular mechanisms of these closely related coronaviruses. The TGF-? pathway, known for its involvement in tissue fibrosis, was specifically dysregulated by SARS-CoV-2 ORF8 and autophagy by SARS-CoV-2 ORF3. The extensive dataset (available at https://covinet.innatelab.org ) highlights many hotspots that can be targeted by existing drugs and it can guide rational design of virus- and host-directed therapies, which we exemplify by identifying kinase and MMPs inhibitors with potent antiviral effects against SARS-CoV-2.
. 2021 Apr 12.
doi: 10.1038/s41586-021-03493-4. Online ahead of print.
Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV
Alexey Stukalov[SUP] #[/SUP][SUP] 1 [/SUP], Virginie Girault[SUP] #[/SUP][SUP] 1 [/SUP], Vincent Grass[SUP] #[/SUP][SUP] 1 [/SUP], Ozge Karayel[SUP] #[/SUP][SUP] 2 [/SUP], Valter Bergant[SUP] #[/SUP][SUP] 1 [/SUP], Christian Urban[SUP] #[/SUP][SUP] 1 [/SUP], Darya A Haas[SUP] #[/SUP][SUP] 1 [/SUP], Yiqi Huang[SUP] #[/SUP][SUP] 1 [/SUP], Lila Oubraham[SUP] 1 [/SUP], Anqi Wang[SUP] 1 [/SUP], M Sabri Hamad[SUP] 1 [/SUP], Antonio Piras[SUP] 1 [/SUP], Fynn M Hansen[SUP] 2 [/SUP], Maria C Tanzer[SUP] 2 [/SUP], Igor Paron[SUP] 2 [/SUP], Luca Zinzula[SUP] 3 [/SUP], Thomas Enghleitner[SUP] 4 [/SUP], Maria Reinecke[SUP] 5 6 [/SUP], Teresa M Lavacca[SUP] 1 [/SUP], Rosina Ehmann[SUP] 7 8 [/SUP], Roman W?lfel[SUP] 7 8 [/SUP], J?rg Jores[SUP] 9 [/SUP], Bernhard Kuster[SUP] 5 6 [/SUP], Ulrike Protzer[SUP] 1 8 [/SUP], Roland Rad[SUP] 4 [/SUP], John Ziebuhr[SUP] 10 [/SUP], Volker Thiel[SUP] 11 [/SUP], Pietro Scaturro[SUP] 1 12 [/SUP], Matthias Mann[SUP] 2 [/SUP], Andreas Pichlmair[SUP] 13 14 [/SUP]
Affiliations
- PMID: 33845483
- DOI: 10.1038/s41586-021-03493-4
Abstract
The 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 individual omics studies have extended our knowledge of COVID-19 pathophysiology[SUP]1-10[/SUP]. 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. We therefore conducted a concurrent multi-omics study of SARS-CoV-2 and SARS-CoV. Using state-of-the-art proteomics, we profiled the interactome of both viruses, as well as their influence on transcriptome, proteome, ubiquitinome and phosphoproteome in a lung-derived human cell line. Projecting these data onto the global network of cellular interactions revealed crosstalk between the perturbations taking place upon SARS-CoV-2 and SARS-CoV infections at different layers and identified unique and common molecular mechanisms of these closely related coronaviruses. The TGF-? pathway, known for its involvement in tissue fibrosis, was specifically dysregulated by SARS-CoV-2 ORF8 and autophagy by SARS-CoV-2 ORF3. The extensive dataset (available at https://covinet.innatelab.org ) highlights many hotspots that can be targeted by existing drugs and it can guide rational design of virus- and host-directed therapies, which we exemplify by identifying kinase and MMPs inhibitors with potent antiviral effects against SARS-CoV-2.