The Global Phosphorylation Landscape of SARS-CoV-2 Infection

Copyright © 2020 Elsevier Inc. All rights reserved..

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 MAPK activation, production of diverse cytokines, and shutdown of mitotic kinases, resulting in cell cycle arrest. Infection also stimulated a marked induction of CK2-containing filopodial 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 the p38, CK2, CDK, AXL, and PIKFYVE kinases to possess antiviral efficacy, representing potential COVID-19 therapies.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:182

Enthalten in:

Cell - 182(2020), 3 vom: 06. Aug., Seite 685-712.e19

Sprache:

Englisch

Beteiligte Personen:

Bouhaddou, Mehdi [VerfasserIn]
Memon, Danish [VerfasserIn]
Meyer, Bjoern [VerfasserIn]
White, Kris M [VerfasserIn]
Rezelj, Veronica V [VerfasserIn]
Correa Marrero, Miguel [VerfasserIn]
Polacco, Benjamin J [VerfasserIn]
Melnyk, James E [VerfasserIn]
Ulferts, Svenja [VerfasserIn]
Kaake, Robyn M [VerfasserIn]
Batra, Jyoti [VerfasserIn]
Richards, Alicia L [VerfasserIn]
Stevenson, Erica [VerfasserIn]
Gordon, David E [VerfasserIn]
Rojc, Ajda [VerfasserIn]
Obernier, Kirsten [VerfasserIn]
Fabius, Jacqueline M [VerfasserIn]
Soucheray, Margaret [VerfasserIn]
Miorin, Lisa [VerfasserIn]
Moreno, Elena [VerfasserIn]
Koh, Cassandra [VerfasserIn]
Tran, Quang Dinh [VerfasserIn]
Hardy, Alexandra [VerfasserIn]
Robinot, Rémy [VerfasserIn]
Vallet, Thomas [VerfasserIn]
Nilsson-Payant, Benjamin E [VerfasserIn]
Hernandez-Armenta, Claudia [VerfasserIn]
Dunham, Alistair [VerfasserIn]
Weigang, Sebastian [VerfasserIn]
Knerr, Julian [VerfasserIn]
Modak, Maya [VerfasserIn]
Quintero, Diego [VerfasserIn]
Zhou, Yuan [VerfasserIn]
Dugourd, Aurelien [VerfasserIn]
Valdeolivas, Alberto [VerfasserIn]
Patil, Trupti [VerfasserIn]
Li, Qiongyu [VerfasserIn]
Hüttenhain, Ruth [VerfasserIn]
Cakir, Merve [VerfasserIn]
Muralidharan, Monita [VerfasserIn]
Kim, Minkyu [VerfasserIn]
Jang, Gwendolyn [VerfasserIn]
Tutuncuoglu, Beril [VerfasserIn]
Hiatt, Joseph [VerfasserIn]
Guo, Jeffrey Z [VerfasserIn]
Xu, Jiewei [VerfasserIn]
Bouhaddou, Sophia [VerfasserIn]
Mathy, Christopher J P [VerfasserIn]
Gaulton, Anna [VerfasserIn]
Manners, Emma J [VerfasserIn]
Félix, Eloy [VerfasserIn]
Shi, Ying [VerfasserIn]
Goff, Marisa [VerfasserIn]
Lim, Jean K [VerfasserIn]
McBride, Timothy [VerfasserIn]
O'Neal, Michael C [VerfasserIn]
Cai, Yiming [VerfasserIn]
Chang, Jason C J [VerfasserIn]
Broadhurst, David J [VerfasserIn]
Klippsten, Saker [VerfasserIn]
De Wit, Emmie [VerfasserIn]
Leach, Andrew R [VerfasserIn]
Kortemme, Tanja [VerfasserIn]
Shoichet, Brian [VerfasserIn]
Ott, Melanie [VerfasserIn]
Saez-Rodriguez, Julio [VerfasserIn]
tenOever, Benjamin R [VerfasserIn]
Mullins, R Dyche [VerfasserIn]
Fischer, Elizabeth R [VerfasserIn]
Kochs, Georg [VerfasserIn]
Grosse, Robert [VerfasserIn]
García-Sastre, Adolfo [VerfasserIn]
Vignuzzi, Marco [VerfasserIn]
Johnson, Jeffery R [VerfasserIn]
Shokat, Kevan M [VerfasserIn]
Swaney, Danielle L [VerfasserIn]
Beltrao, Pedro [VerfasserIn]
Krogan, Nevan J [VerfasserIn]

Links:

Volltext

Themen:

ACE2 protein, human
AXL
Angiotensin-Converting Enzyme 2
Antiviral
Antiviral Agents
Axl Receptor Tyrosine Kinase
CDK
Casein Kinase II
Casein kinase II
Cyclin-Dependent Kinases
EC 2.7.1.137
EC 2.7.10.1
EC 2.7.11.1
EC 2.7.11.22
EC 2.7.11.24
EC 3.4.15.1
EC 3.4.17.23
Journal Article
MAPK
Mass spectrometry
P38
P38 Mitogen-Activated Protein Kinases
PIKFYVE
PIKFYVE protein, human
Peptidyl-Dipeptidase A
Phosphoinositide-3 Kinase Inhibitors
Phosphoproteomics
Protein Kinase Inhibitors
Proto-Oncogene Proteins
Receptor Protein-Tyrosine Kinases
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
SARS-CoV-2
Spike Glycoprotein, Coronavirus
Spike protein, SARS-CoV-2

Anmerkungen:

Date Completed 28.08.2020

Date Revised 16.02.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.cell.2020.06.034

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM312221347