509917399

Growth factor receptor signaling inhibition prevents SARS-CoV-2 replication / Kevin Klann, Denisa Bojkova, Georg Tascher, Sandra Ciesek, Christian Münch, Jindrich Cinatl

Klann, Kevin,i1991- [Verfasser] ; Bojkova, Denisa,i1991- [Verfasser] ; Tascher, Georg,i1981- [Verfasser] ; Ciesek, Sandra,i1978- [Verfasser] ; Münch, Christian [Verfasser] ; Cinatl, Jindrich [Verfasser]

Preprint

2020

Frankfurt am Main : Universitätsbibliothek Johann Christian Senckenberg

3 Online-Ressourcen : Illustrationen, Diagramme

Später erschienen in: Molecular Cell, Volume 80, Issue 1, 1 October 2020, Pages 164-174.e4

 

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Open Access

CC BY-​NC-ND 4.0

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SARS-CoV-2 infections are rapidly spreading around the globe. The rapid development of therapies is of major importance. However, our lack of understanding of the molecular processes and host cell signaling events underlying SARS-CoV-2 infection hinder therapy development. We employed a SARS-CoV-2 infection system in permissible human cells to study signaling changes by phospho-proteomics. We identified viral protein phosphorylation and defined phosphorylation-driven host cell signaling changes upon infection. Growth factor receptor (GFR) signaling and downstream pathways were activated. Drug-protein network analyses revealed GFR signaling as key pathway targetable by approved drugs. Inhibition of GFR downstream signaling by five compounds prevented SARS-CoV-2 replication in cells, assessed by cytopathic effect, viral dsRNA production, and viral RNA release into the supernatant. This study describes host cell signaling events upon SARS-CoV-2 infection and reveals GFR signaling as central pathway essential for SARS-CoV-2 replication. It provides with novel strategies for COVID-19 treatment.