M. Bouhaddou, D. Memon, B. Meyer, K. White, Veronica V. Rezelj, Miguel Correa Marrero, B. Polacco, James E. Melnyk, S. Ulferts, Robyn M. Kaake, J. Batra, Alicia L. Richards, Erica Stevenson, D. E. Gordon, Ajda Rojc, K. Obernier, Jacqueline M. Fabius, Margaret Soucheray, L. Miorin, Elena Moreno, C. Koh, Q. D. Tran, Alexandra Hardy, R. Robinot, T. Vallet, Benjamin E. Nilsson-Payant, Claudia Hernandez-Armenta, Alistair S Dunham, S. Weigang, Julian Knerr, Mayank Modak, Diego Quintero, Yuan Zhou, Aurélien Dugourd, A. Valdeolivas, T. Patil, Qiongyu Li, Ruth Hüttenhain, Merve Cakir, Monita Muralidharan, Minkyu Kim, Gwendolyn M. Jang, B. Tutuncuoglu, J. Hiatt, Jeffrey Z. Guo, Jiewei Xu, Sophia Bouhaddou, C. J. Mathy, A. Gaulton, Emma J. Manners, Eloy Felix, Ying Shi, Marisa A. Goff, Jean K. Lim, Timothy Mcbride, M. C. O’Neal, Yiming Cai, J. C. Chang, D. Broadhurst, Saker Klippsten, E. de Wit, A. Leach, T. Kortemme, B. Shoichet, M. Ott, J. Saez-Rodriguez, B. tenOever, R. Mullins, E. Fischer, G. Kochs, R. Grosse, A. García-Sastre, M. Vignuzzi, J. R. Johnson, K. Shokat, D. Swaney, P. Beltrão, N. Krogan
Cell, 2020
Summary 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.
Cited by 224 publications.
Field of study: Biology