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Supplemental Information
Table S1 Phosphorylation and Abundance Data, Related to Figure 1
Contains proteomic data of Vero E6 cells upon SARS-CoV-2 infection. Find the full list of unfiltered phosphorylation sites occurring upon SARS-CoV-2 infection (PhosphoDataFull tab), full list of protein abundance measurements (AbundanceDataFull tab), and filtered list of all detected phosphorylation sites collapsed into single-site measurements (PhosphoDataFiltered tab). Lastly, find the full list of unfiltered phosphorylation sites upon N protein overexpression in Vero E6 cells (PhosphoNOverexpressionFull tab). Column descriptions are indicated in the final tab.
Table S2 Viral Phosphorylation Sites, Related to Figure 2
List of phosphosites found on viral proteins from this study as well as from Davidson et al. (2020).
Table S3 Enrichments, Related to Figures 1, 4, and S1
Gene ontology enrichments for significantly changed phosphorylation sites (Enrichment.Phosphorylation tab), significantly changed protein abundance (Enrichment.Abundance tab), and phosphorylation dynamics clusters (from Figure 4A) upon SARS-CoV-2 infection (Enrichment.Ph_Clusters tab). Column descriptions are indicated in the final tab.
Table S4 Predicted Kinase Activities, Related to Figure 4
Full results of predicted kinase activities for each time point post infection with SARS-CoV-2 (Kinase Act. Viral Infection tab) and N protein overexpression (Kinase Act. N Overexpression tab). Kinase activities are inferred as a -log10(p value) of Z-test from the comparison of fold changes in phosphosite measurements of the known substrates against the overall distribution of fold changes across the sample. Kinase activities possessing any absolute value change greater than 1.5 are indicated. Column descriptions are indicated in the final tab.
Table S5 Prioritized Phosphorylation Site Review, Related to Figure 7 and Table S8
Significantly regulated phosphorylation sites upon SARS-CoV-2 infection prioritized as either annotated within the PhosphoSitePlus database or possessing a high functional score (> = 0.75) (Ochoa et al. 2020). Includes literature context for prioritized phosphorylation sites, including their known functions and proposed relevance to SARS-CoV-2 pathogenesis. Phosphorylation sites are partitioned into eight biological contexts.
Table S6 Predicted Transcription Factor Activities, Related to Figure 6
Full results of computed transcription factor activities from RNA-seq analysis of SARS-CoV-2 infected human lung cell lines (GSE147507) (Blanco-Melo et al. 2020) using DoRothEA (Garcia-Alonso et al. 2019). Gene symbols, NES scores, and cell lines are depicted.
Table S7 Cytokine Profiling Data, Related to Figure 6
Results from Luminex profiling of SARS-CoV-2 infected ACE2-A549 cells pre-treated with p38 inhibitor SB203580. Supernatants from infected cells were evaluated for 34 cytokines/chemokines. Units are pg/mL.
Table S8 Drugs and Compounds, Related to Figures 7 and S5 and Tables S4 and S5
Drugs and compounds mapped to top kinase activities (Table S4) and prioritized phosphorylation sites (Table S5). DrugInfo tab depicts known protein targets, approval status, SMILES, supplier, catalog numbers, chembl IDs, annotation of test site and cell line in which tests were performed, IC50 (viral inhibition) and CC50 (cell viability) values for pharmacological profiling. FullDrugResponseData tab depicts mean and standard deviation for drug screening experiments depicted in Figure S5.

Acknowledgments
This research was funded by grants from the 10.13039/100000002National Institutes of Health (P50AI150476, U19AI135990, U19AI135972, R01AI143292, R01AI120694, P01A1063302, and R01AI122747 to N.J.K.; 1R01CA221969 and 1R01CA244550 to K.M.S.; R01GM133981 to D.L.S.; 1F32CA236347-01 to J.E.M.; U19AI118610 to J.R.J.; and F32CA239333 to M.B.), Defense Advance Research Projects Agency HR0011-19-2-0020 (to N.J.K., A.G.S., and K.M.S.); by the Laboratory for Genomics Research (LGR) Excellence in Research Award (ERA) from the 10.13039/100014220Innovative Genomics Institute at UC Berkeley (grant number 133122P); by CRIP (Center for Research for Influenza Pathogenesis), a NIAID-supported Center of Excellence for Influenza Research and Surveillance (CEIRS; contract HHSN272201400008C) (to A.G.S.); by supplements to 10.13039/100000060NIAID grant U19AI135972 and DoD grant W81XWH-19-PRMRP-FPA (to A.G.S.); and by the generous support of the 10.13039/100007457JPB Foundation, the Open Philanthropy Project (research grant 2020-215611 [5384]), and other philanthropic donations (to A.G.S.); by the Laboratoire d’Excellence “Integrative Biology of Emerging Infectious Diseases” grant ANR-10-LABX-62-IBEID (to M.V.); by the DFG under Germany's Excellence Strategy (EXC-2189, project ID 390939984 to R.G.); by a Starting Grant Award from the 10.13039/501100000781European Research Council (ERC-2014-STG 638884 PhosFunc to P.B.); by the 10.13039/501100002347Federal Ministry of Education and Research (BMBF, Computational Life Sciences grant 031L0181B to J.S.R.); by the Intramural Research Program of the 10.13039/100000002NIH, 10.13039/100000060National Institute of Allergy and Infectious Diseases (to E.R.F. and E.D.W.); and by funding from 10.13039/100007013F. Hoffmann-La Roche and Vir Biotechnology and gifts from The Ron Conway Family. K.M.S. is an investigator of the Howard Hughes Medical Institute. The views, opinions, and findings contained in this study are those of the authors and do not represent the official views, policies, or endorsement of the Department of Defense or the U.S. Government. We would like to acknowledge Desiree Ho, Innovative Genomics Institute, for SARS-CoV-2 virus illustrations. We thank Randy Albert for support with the BSL3 facility and procedures at the Icahn School of Medicine at Mount Sinai, New York.

Author Contributions
Conceptualization, M.B., D.L.S., and N.J.K.; Infection Experiments, B.M., V.V.R., B.E.N., L.M., C.K., Q.D.T., A.H., T.V., K.M.W., and E.M.; Proteomics Sample Coordination and Preparation, E.S., M.S., J.M.F., J.Z.G., and J.X.; Proteomics Data Acquisition, A.L.R. and D.L.S.; Data Analysis, M.C.M., B.J.P., D.M., C.H.-A., A. Dunham, M. Modak, D.Q., Y.Z., J.R.J., D.L.S., P.B., J.K.L., M.G., M.B., and C.J.P.M.; Figure Generation, M.C.M., B.J.P., D.M., C.H.-A., A. Dunham, M. Modak, D.Q., J.R.J., D.L.S., P.B., and M.B.; Cell Cycle Experiments, R.R. and B.M.; Infection Imaging, S.W., J.K., S.U., G.K., and R.G.; Manuscript Preparation, M.B., D.E.G., K.O., J.R.J., D.L.S., P.B., N.J.K., and R.D.M.; Literature Review, by R.M.K., M. Modak, J.B., A.R., T.P., Q.L., R.H., M.C., M. Muralidharan, M.K., G.J., B.T., J.H., D.L.S., and M.B.; RNA-seq Analysis, A. Dugourd, A.V., and J.S.-R.; Drug Curation, Y.S., J.E.M., K.M.S., A.R.L., E.J.M., E.F., and S.B.; Interactive Map, T.M., M.C.O., Y.C., J.C.J.C., D.J.B, S.K., M.B., and R.M.K.; Electron Microscopy, E.R.F. and E.D.w.; Work Supervision, T.K., J.K.L., A.G., B.S., M.O., J.S.-R., G.K., R.G., B.R.t., K.M.S., J.R.J., D.L.S., A.G.-S., M.V., P.B., and N.J.K.

Declaration of Interests
The Krogan laboratory has received research support from Vir Biotechnology and F. Hoffmann-La Roche. K.M.S. has consulting agreements for the following companies involving cash and/or stock compensation: Black Diamond Therapeutics, BridGene Biosciences, Denali Therapeutics, Dice Molecules, eFFECTOR Therapeutics (zotatifin and tomivosertib), Erasca, Genentech/Roche, Janssen Pharmaceuticals, Kumquat Biosciences, Kura Oncology, Merck, Mitokinin, Petra Pharma, Qulab Inc. Revolution Medicines (WDB002), Type6 Therapeutics, Venthera, and Wellspring Biosciences (Araxes Pharma). Supplemental Information can be found online at https://doi.org/10.1016/j.cell.2020.06.034.