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 |
---|
Links: |
---|
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 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | NLM312221347 | ||
003 | DE-627 | ||
005 | 20240216232051.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231225s2020 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1016/j.cell.2020.06.034 |2 doi | |
028 | 5 | 2 | |a pubmed24n1295.xml |
035 | |a (DE-627)NLM312221347 | ||
035 | |a (NLM)32645325 | ||
035 | |a (PII)S0092-8674(20)30811-4 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Bouhaddou, Mehdi |e verfasserin |4 aut | |
245 | 1 | 4 | |a The Global Phosphorylation Landscape of SARS-CoV-2 Infection |
264 | 1 | |c 2020 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 28.08.2020 | ||
500 | |a Date Revised 16.02.2024 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Copyright © 2020 Elsevier Inc. All rights reserved. | ||
520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, N.I.H., Extramural | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
650 | 4 | |a AXL | |
650 | 4 | |a CDK | |
650 | 4 | |a MAPK | |
650 | 4 | |a PIKFYVE | |
650 | 4 | |a SARS-CoV-2 | |
650 | 4 | |a antiviral | |
650 | 4 | |a casein kinase II | |
650 | 4 | |a mass spectrometry | |
650 | 4 | |a p38 | |
650 | 4 | |a phosphoproteomics | |
650 | 7 | |a Antiviral Agents |2 NLM | |
650 | 7 | |a Phosphoinositide-3 Kinase Inhibitors |2 NLM | |
650 | 7 | |a Protein Kinase Inhibitors |2 NLM | |
650 | 7 | |a Proto-Oncogene Proteins |2 NLM | |
650 | 7 | |a Spike Glycoprotein, Coronavirus |2 NLM | |
650 | 7 | |a spike protein, SARS-CoV-2 |2 NLM | |
650 | 7 | |a PIKFYVE protein, human |2 NLM | |
650 | 7 | |a EC 2.7.1.137 |2 NLM | |
650 | 7 | |a Receptor Protein-Tyrosine Kinases |2 NLM | |
650 | 7 | |a EC 2.7.10.1 |2 NLM | |
650 | 7 | |a Casein Kinase II |2 NLM | |
650 | 7 | |a EC 2.7.11.1 |2 NLM | |
650 | 7 | |a Cyclin-Dependent Kinases |2 NLM | |
650 | 7 | |a EC 2.7.11.22 |2 NLM | |
650 | 7 | |a p38 Mitogen-Activated Protein Kinases |2 NLM | |
650 | 7 | |a EC 2.7.11.24 |2 NLM | |
650 | 7 | |a Peptidyl-Dipeptidase A |2 NLM | |
650 | 7 | |a EC 3.4.15.1 |2 NLM | |
650 | 7 | |a ACE2 protein, human |2 NLM | |
650 | 7 | |a EC 3.4.17.23 |2 NLM | |
650 | 7 | |a Angiotensin-Converting Enzyme 2 |2 NLM | |
650 | 7 | |a EC 3.4.17.23 |2 NLM | |
650 | 7 | |a Axl Receptor Tyrosine Kinase |2 NLM | |
700 | 1 | |a Memon, Danish |e verfasserin |4 aut | |
700 | 1 | |a Meyer, Bjoern |e verfasserin |4 aut | |
700 | 1 | |a White, Kris M |e verfasserin |4 aut | |
700 | 1 | |a Rezelj, Veronica V |e verfasserin |4 aut | |
700 | 1 | |a Correa Marrero, Miguel |e verfasserin |4 aut | |
700 | 1 | |a Polacco, Benjamin J |e verfasserin |4 aut | |
700 | 1 | |a Melnyk, James E |e verfasserin |4 aut | |
700 | 1 | |a Ulferts, Svenja |e verfasserin |4 aut | |
700 | 1 | |a Kaake, Robyn M |e verfasserin |4 aut | |
700 | 1 | |a Batra, Jyoti |e verfasserin |4 aut | |
700 | 1 | |a Richards, Alicia L |e verfasserin |4 aut | |
700 | 1 | |a Stevenson, Erica |e verfasserin |4 aut | |
700 | 1 | |a Gordon, David E |e verfasserin |4 aut | |
700 | 1 | |a Rojc, Ajda |e verfasserin |4 aut | |
700 | 1 | |a Obernier, Kirsten |e verfasserin |4 aut | |
700 | 1 | |a Fabius, Jacqueline M |e verfasserin |4 aut | |
700 | 1 | |a Soucheray, Margaret |e verfasserin |4 aut | |
700 | 1 | |a Miorin, Lisa |e verfasserin |4 aut | |
700 | 1 | |a Moreno, Elena |e verfasserin |4 aut | |
700 | 1 | |a Koh, Cassandra |e verfasserin |4 aut | |
700 | 1 | |a Tran, Quang Dinh |e verfasserin |4 aut | |
700 | 1 | |a Hardy, Alexandra |e verfasserin |4 aut | |
700 | 1 | |a Robinot, Rémy |e verfasserin |4 aut | |
700 | 1 | |a Vallet, Thomas |e verfasserin |4 aut | |
700 | 1 | |a Nilsson-Payant, Benjamin E |e verfasserin |4 aut | |
700 | 1 | |a Hernandez-Armenta, Claudia |e verfasserin |4 aut | |
700 | 1 | |a Dunham, Alistair |e verfasserin |4 aut | |
700 | 1 | |a Weigang, Sebastian |e verfasserin |4 aut | |
700 | 1 | |a Knerr, Julian |e verfasserin |4 aut | |
700 | 1 | |a Modak, Maya |e verfasserin |4 aut | |
700 | 1 | |a Quintero, Diego |e verfasserin |4 aut | |
700 | 1 | |a Zhou, Yuan |e verfasserin |4 aut | |
700 | 1 | |a Dugourd, Aurelien |e verfasserin |4 aut | |
700 | 1 | |a Valdeolivas, Alberto |e verfasserin |4 aut | |
700 | 1 | |a Patil, Trupti |e verfasserin |4 aut | |
700 | 1 | |a Li, Qiongyu |e verfasserin |4 aut | |
700 | 1 | |a Hüttenhain, Ruth |e verfasserin |4 aut | |
700 | 1 | |a Cakir, Merve |e verfasserin |4 aut | |
700 | 1 | |a Muralidharan, Monita |e verfasserin |4 aut | |
700 | 1 | |a Kim, Minkyu |e verfasserin |4 aut | |
700 | 1 | |a Jang, Gwendolyn |e verfasserin |4 aut | |
700 | 1 | |a Tutuncuoglu, Beril |e verfasserin |4 aut | |
700 | 1 | |a Hiatt, Joseph |e verfasserin |4 aut | |
700 | 1 | |a Guo, Jeffrey Z |e verfasserin |4 aut | |
700 | 1 | |a Xu, Jiewei |e verfasserin |4 aut | |
700 | 1 | |a Bouhaddou, Sophia |e verfasserin |4 aut | |
700 | 1 | |a Mathy, Christopher J P |e verfasserin |4 aut | |
700 | 1 | |a Gaulton, Anna |e verfasserin |4 aut | |
700 | 1 | |a Manners, Emma J |e verfasserin |4 aut | |
700 | 1 | |a Félix, Eloy |e verfasserin |4 aut | |
700 | 1 | |a Shi, Ying |e verfasserin |4 aut | |
700 | 1 | |a Goff, Marisa |e verfasserin |4 aut | |
700 | 1 | |a Lim, Jean K |e verfasserin |4 aut | |
700 | 1 | |a McBride, Timothy |e verfasserin |4 aut | |
700 | 1 | |a O'Neal, Michael C |e verfasserin |4 aut | |
700 | 1 | |a Cai, Yiming |e verfasserin |4 aut | |
700 | 1 | |a Chang, Jason C J |e verfasserin |4 aut | |
700 | 1 | |a Broadhurst, David J |e verfasserin |4 aut | |
700 | 1 | |a Klippsten, Saker |e verfasserin |4 aut | |
700 | 1 | |a De Wit, Emmie |e verfasserin |4 aut | |
700 | 1 | |a Leach, Andrew R |e verfasserin |4 aut | |
700 | 1 | |a Kortemme, Tanja |e verfasserin |4 aut | |
700 | 1 | |a Shoichet, Brian |e verfasserin |4 aut | |
700 | 1 | |a Ott, Melanie |e verfasserin |4 aut | |
700 | 1 | |a Saez-Rodriguez, Julio |e verfasserin |4 aut | |
700 | 1 | |a tenOever, Benjamin R |e verfasserin |4 aut | |
700 | 1 | |a Mullins, R Dyche |e verfasserin |4 aut | |
700 | 1 | |a Fischer, Elizabeth R |e verfasserin |4 aut | |
700 | 1 | |a Kochs, Georg |e verfasserin |4 aut | |
700 | 1 | |a Grosse, Robert |e verfasserin |4 aut | |
700 | 1 | |a García-Sastre, Adolfo |e verfasserin |4 aut | |
700 | 1 | |a Vignuzzi, Marco |e verfasserin |4 aut | |
700 | 1 | |a Johnson, Jeffery R |e verfasserin |4 aut | |
700 | 1 | |a Shokat, Kevan M |e verfasserin |4 aut | |
700 | 1 | |a Swaney, Danielle L |e verfasserin |4 aut | |
700 | 1 | |a Beltrao, Pedro |e verfasserin |4 aut | |
700 | 1 | |a Krogan, Nevan J |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Cell |d 1974 |g 182(2020), 3 vom: 06. Aug., Seite 685-712.e19 |w (DE-627)NLM000088935 |x 1097-4172 |7 nnns |
773 | 1 | 8 | |g volume:182 |g year:2020 |g number:3 |g day:06 |g month:08 |g pages:685-712.e19 |
856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.cell.2020.06.034 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 182 |j 2020 |e 3 |b 06 |c 08 |h 685-712.e19 |