The Global Phosphorylation Landscape of SARS-CoV-2 Infection. Bouhaddou et al., 2020.

Published: 22 June 2020| Version 1 | DOI: 10.17632/dpkbh2g9hy.1
Contributors:
Mehdi Bouhaddou,
Danish Memon,
Bjoern Meyer,
Kris White,
Veronica Rezelj,
Miguel Marrero,
Benjamin Polacco,
James Melnyk,
Svenja Ulferts,
Robyn Kaake,
Jyoti Batra,
Robert Grosse,
Adolfo Garcia-Sastre,
Marco Vignuzzi,
Jeffrey Johnson,
Kevan Shokat,
Danielle Swaney,
Pedro Beltrao,
Nevan Krogan

Description

The causative agent of the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected millions and killed hundreds of thousands of people worldwide, highlighting an urgent need to develop antiviral therapies. Here, we present a quantitative mass spectrometry- based phosphoproteomics survey of SARS-CoV-2 infection in Vero E6 cells, revealing dramatic rewiring of phosphorylation on host and viral proteins. SARS-CoV-2 infection promoted casein kinase II (CK2) and p38 MAP kinase activation, production of diverse cytokines, and shutdown of mitotic kinases resulting in cell cycle arrest. Infection also stimulated a marked induction of CK2-containing filopodia protrusions possessing budding viral particles. Eighty-seven drugs and compounds were identified by mapping global phosphorylation profiles to dysregulated kinases and pathways. We found pharmacologic inhibition of p38, CK2, CDKs, AXL and PIKFYVE kinases to possess antiviral efficacy, representing potential COVID-19 therapies.

Files

Categories

Pharmacology, Systems Biology, Mass Spectrometry, Proteomics, Phosphorylation, Kinase Signaling, Antiviral, Severe Acute Respiratory Syndrome Coronavirus 2

License