| Literature DB >> 32645325 |
Mehdi Bouhaddou1, Danish Memon2, Bjoern Meyer3, Kris M White4, Veronica V Rezelj3, Miguel Correa Marrero2, Benjamin J Polacco1, James E Melnyk5, Svenja Ulferts6, Robyn M Kaake1, Jyoti Batra1, Alicia L Richards1, Erica Stevenson1, David E Gordon1, Ajda Rojc1, Kirsten Obernier1, Jacqueline M Fabius1, Margaret Soucheray1, Lisa Miorin4, Elena Moreno4, Cassandra Koh3, Quang Dinh Tran3, Alexandra Hardy3, Rémy Robinot7, Thomas Vallet3, Benjamin E Nilsson-Payant8, Claudia Hernandez-Armenta2, Alistair Dunham2, Sebastian Weigang9, Julian Knerr6, Maya Modak1, Diego Quintero1, Yuan Zhou1, Aurelien Dugourd10, Alberto Valdeolivas10, Trupti Patil1, Qiongyu Li1, Ruth Hüttenhain1, Merve Cakir1, Monita Muralidharan1, Minkyu Kim1, Gwendolyn Jang1, Beril Tutuncuoglu1, Joseph Hiatt1, Jeffrey Z Guo1, Jiewei Xu1, Sophia Bouhaddou11, Christopher J P Mathy12, Anna Gaulton2, Emma J Manners2, Eloy Félix2, Ying Shi5, Marisa Goff8, Jean K Lim8, Timothy McBride13, Michael C O'Neal13, Yiming Cai13, Jason C J Chang13, David J Broadhurst13, Saker Klippsten13, Emmie De Wit14, Andrew R Leach2, Tanja Kortemme12, Brian Shoichet15, Melanie Ott16, Julio Saez-Rodriguez10, Benjamin R tenOever8, R Dyche Mullins5, Elizabeth R Fischer14, Georg Kochs17, Robert Grosse18, Adolfo García-Sastre19, Marco Vignuzzi20, Jeffery R Johnson21, Kevan M Shokat22, Danielle L Swaney23, Pedro Beltrao24, Nevan J Krogan25.
Abstract
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.Entities:
Keywords: AXL; CDK; MAPK; PIKFYVE; SARS-CoV-2; antiviral; casein kinase II; mass spectrometry; p38; phosphoproteomics
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Year: 2020 PMID： 32645325 PMCID： PMC7321036 DOI： 10.1016/j.cell.2020.06.034
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582