PT  - JOURNAL ARTICLE
AU  - Alexey Stukalov
AU  - Virginie Girault
AU  - Vincent Grass
AU  - Valter Bergant
AU  - Ozge Karayel
AU  - Christian Urban
AU  - Darya A. Haas
AU  - Yiqi Huang
AU  - Lila Oubraham
AU  - Anqi Wang
AU  - Sabri M. Hamad
AU  - Antonio Piras
AU  - Maria Tanzer
AU  - Fynn M. Hansen
AU  - Thomas Enghleitner
AU  - Maria Reinecke
AU  - Teresa M. Lavacca
AU  - Rosina Ehmann
AU  - Roman Wölfel
AU  - Jörg Jores
AU  - Bernhard Kuster
AU  - Ulrike Protzer
AU  - Roland Rad
AU  - John Ziebuhr
AU  - Volker Thiel
AU  - Pietro Scaturro
AU  - Matthias Mann
AU  - Andreas Pichlmair
TI  - Multi-level proteomics reveals host-perturbation strategies of SARS-CoV-2 and SARS-CoV
AID  - 10.1101/2020.06.17.156455
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.06.17.156455
4099  - http://biorxiv.org/content/early/2020/06/17/2020.06.17.156455.short
4100  - http://biorxiv.org/content/early/2020/06/17/2020.06.17.156455.full
AB  - The sudden 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 omics studies have extended our knowledge of COVID-19 pathophysiology, including some focused on proteomic aspects1–3. To understand how SARS-CoV-2 and related coronaviruses manipulate the host we here characterized interactome, proteome and signaling processes in a systems-wide manner. This identified connections between the corresponding cellular events, revealed functional effects of the individual viral proteins and put these findings into the context of host signaling pathways. We investigated the closely related SARS-CoV-2 and SARS-CoV viruses as well as the influence of SARS-CoV-2 on transcriptome, proteome, ubiquitinome and phosphoproteome of a lung-derived human cell line. Projecting these data onto the global network of cellular interactions revealed relationships between the perturbations taking place upon SARS-CoV-2 infection at different layers and identified unique and common molecular mechanisms of SARS coronaviruses. The results highlight the functionality of individual proteins as well as vulnerability hotspots of SARS-CoV-2, which we targeted with clinically approved drugs. We exemplify this by identification of kinase inhibitors as well as MMPase inhibitors with significant antiviral effects against SARS-CoV-2.Competing Interest StatementThe authors have declared no competing interest.