RT Journal Article
SR Electronic
T1 Multi-level proteomics reveals host-perturbation strategies of SARS-CoV-2 and SARS-CoV
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.06.17.156455
DO 10.1101/2020.06.17.156455
A1 Alexey Stukalov
A1 Virginie Girault
A1 Vincent Grass
A1 Valter Bergant
A1 Ozge Karayel
A1 Christian Urban
A1 Darya A. Haas
A1 Yiqi Huang
A1 Lila Oubraham
A1 Anqi Wang
A1 Sabri M. Hamad
A1 Antonio Piras
A1 Maria Tanzer
A1 Fynn M. Hansen
A1 Thomas Enghleitner
A1 Maria Reinecke
A1 Teresa M. Lavacca
A1 Rosina Ehmann
A1 Roman Wölfel
A1 Jörg Jores
A1 Bernhard Kuster
A1 Ulrike Protzer
A1 Roland Rad
A1 John Ziebuhr
A1 Volker Thiel
A1 Pietro Scaturro
A1 Matthias Mann
A1 Andreas Pichlmair
YR 2020
UL http://biorxiv.org/content/early/2020/06/17/2020.06.17.156455.abstract
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.