| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T968 |
0-20 |
Sentence |
denotes |
Supporting Citations |
| T969 |
21-85 |
Sentence |
denotes |
The following references appear in the Supplemental Information: |
| T970 |
86-8224 |
Sentence |
denotes |
Abraham et al. (2000); Alfonso et al. (2011); Ali et al. (2000); Amin et al. (2014); Aoh et al. (2009); Araujo et al. (1993); Archambault and Carmena (2012); Aubrey et al. (2016); Auld et al. (2005); Bai et al. (1996); Bakircioglu et al. (2011); Bandau et al. (2012); Barkley et al. (2012); Bartrons et al. (2018); Bassermann et al. (2005); Bayliss et al. (2012); Beeson (2013); Beli et al. (2012); Ben Djoudi Ouadda et al. (2018); Beurel et al. (2015); Biaoxue et al. (2016); Bieling et al. (2008); Bischoff et al. (1990); Bitko et al. (2008); Blethrow et al. (2008); Böck et al. (2010); Boeing et al. (2016); Bradshaw et al. (2013); Brattsand et al. (1994); Bromberg and Darnell (2000); Bruinsma et al. (2014); Byon et al. (1998); Cahill et al. (2016a); Cahill et al. (2016b); Cai et al. (2006); Cai et al. (2007); Casado et al. (2014); Chang et al. (2004); Chen et al. (1999); Chen et al. (2002); Chen et al. (2004); Chen et al. (2009); Chen et al. (2013); Chen et al. (2017); Cheng et al. (1998); Cheng et al. (2000); Chiu et al. (2012); Cho et al. (2019); Chou et al. (1990); Chu et al. (2012); Corkery et al. (2015); Costa-Mattioli et al. (2004); Courcelles et al. (2013); Cox et al. (2003); Das et al. (2018); Das et al. (2019); Day et al. (2010); de Haan and Rottier (2005); Decker and Kovarik (2000); DeDiego et al. (2011); DeDiego et al. (2014); Degryse et al. (2018); Deora et al. (2004); Dephoure et al. (2008); Díaz-Moreno et al. (2009); Dou et al. (2015); Eguchi et al. (2009); Elia et al. (2015); Ellis et al. (2019); Eriksson et al. (2004); Escobar et al. (2015); Eto et al. (2012); Eulalio et al. (2007); Fallahi et al. (2016); Fan et al. (1997); Fan et al. (2018); Fang et al. (2000); Farquar et al. (2008); Feldman et al. (1997); Fleming et al. (2000); Folker et al. (2005); Foltz et al. (2009); Formstecher et al. (2001); Franchin et al. (2015); Frémin et al. (2016); Fujimoto et al. (2017); Gagnon and Delpire (2010); Gao and Luo (2006); Garcia-Moreno et al. (2018); Geuens et al. (2017); Gherzi et al. (2004); Goel et al. (2015); Goldstein et al. (2000); Grzenda et al. (2009); Guo et al. (2017); Hajjar (1991); Hajjar et al. (1994); Halder and Johnson (2011); Handschick et al. (2014); Harder et al. (2014); He et al. (2010); He et al. (2018); Heald and McKeon (1990); Heaton et al. (2016); Hedglin and Benkovic (2015); Hein and Nilsson (2016); Hensley and Kursula (2016); Holz et al. (2005); Hou et al. (2011); Hu et al. (2010); Hu et al. (2013); Hu et al. (2015); Huang and Lai (2001); Huang et al. (2006); Huang et al. (2014); Hwang et al. (2014); Ichimura et al. (2005); Inoki et al. (2002); Inoue et al. (2011); Intine et al. (2003); Ishii et al. (2013); Ishikawa et al. (2015); Izawa and Inagaki (2006); Jacque and Stevenson (2006); Jang et al. (2015); Jiang et al. (2014); Johnson et al. (2011); Kane et al. (2002); Kanzawa et al. (2006); Karin (1995); Kastenhuber and Lowe (2017); Katayama et al. (2004); Kennedy et al. (2017); Khurana and Bhattacharyya (2015); Killoran et al. (2015); Kim et al. (2006); Kindrachuk et al. (2015); Kishimoto et al. (2003); Kjolby et al. (2010); Koff et al. (1992); Kohl et al. (2019); Koseki et al. (1999); Kostenko et al. (2009); Kotula et al. (2013); Kovacina et al. (2003); Kraft et al. (2003); Kramer et al. (1998); Kremer et al. (2007); Kuang et al. (2016); Kumar et al. (2014); Kumar et al. (2018); Kunapuli et al. (2006); Labit et al. (2012); Lamarche-Vane and Hall (1998); Larance et al. (2010); Lau et al. (2006); Law et al. (2007); Le Sage et al. (2016); Lee and Myung (2008); Lee et al. (2011); Lee et al. (2012); Lee et al. (2013); Leite and Way (2015); Lekmine et al. (2003); Lekmine et al. (2004); Leukel and Jost (1995); Levy and Lee (2002); Li and Martinez (2011); Li and Nagy (2011); Li et al. (2007a); Li et al. (2007b); Li et al. (2008); Li et al. (2016); Li et al. (2017); Liang et al. (2016); Liao et al. (2005); Lieberman et al. (2017); Lim et al. (2013); Lin et al. (2009); Lin et al. (2013); Lingel et al. (2017); Lisnock et al. (2000); Liu and Schneider (2013); Liu et al. (2011); Liu et al. (2013); Liu et al. (2015); Lobry et al. (2007); Lokireddy et al. (2015); Long et al. (2014); Lu et al. (2014); Lu et al. (2017); Lubas et al. (2011); Luciani et al. (2000); Lukas et al. (2011); Luo et al. (2005); Ly et al. (2014); Ly et al. (2017); Machado-Neto et al. (2014); Machowska et al. (2015); Madureira et al. (2012); Magnuson et al. (2012); Magron et al. (2015); Mahony et al. (2017); Mancini et al. (2017); Mandl et al. (2005); Manning and Toker (2017); Marcos-Villar et al. (2016); Marklund et al. (1993); Marklund et al. (1996); Marquette et al. (2011); Matsuhashi et al. (2019); Matsumoto et al. (2015); Matsuoka et al. (2003); McCamphill et al. (2015); McClain et al. (2002); Mehellou et al. (2018); Meier and Blobel (1990); Meier and Blobel (1992); Meier and Blobel 1992); Mendoza et al. (2011); Menon et al. (2014); Mizutani et al. (2004); Mo et al. (2012); Moldave (1985); Morris et al. (2017); Muda et al. (1996); Mueller et al. (2007); Müller et al. (2014); Na et al. (2015); Nairn et al. (2001); Nandi et al. (2007); Needham et al. (2019); Nielsen et al. (2001); Ogiso et al. (2004); Ohtsubo et al. (1995); Old et al. (2009); Olsen et al. (2006); Olsen et al. (2010); Oshiro et al. (2007); Palamarchuk et al. (2005); Pan (2010); Paquette et al. (2018); Park et al. (2000); Parplys et al. (2015); Patel et al. (2015); Penzo et al. (2019); Pfeiffer et al. (2011); Pires et al. (2017); Ponnam et al. (2019); Popov (2012); Poppe et al. (2017); Potter et al. (2002); Potthoff and Olson (2007); Preisinger et al. (2004); Proteau et al. (2005); Qiao et al. (2016); Qiu et al. (2016); Radic (2016); Radtke et al. (2006); Radulescu and Cleveland (2010); Rahim et al. (2018); Rai et al. (2017); Ramm et al. (2006); Raught et al. (2004); Ravichandran et al. (2001); Rebeaud et al. (2008); Renganathan et al. (2005); Revenko et al. (2010); Riad et al. (2018); Robinson et al. (2018); Robinson-White and Stratakis (2002); Robitaille et al. (2013); Rogalla et al. (1999); Rogers et al. (2015); Roy et al. (2014); Roy et al. (2017); Ryan et al. (2016); Salvi et al. (2009); Sanborn et al. (2011); Sánchez-Martín and Komatsu (2018); Santamaria et al. (2003); Saredi et al. (1997); Schmucker and Sumara (2014); Schweppe et al. (2013); Sengupta et al. (2013); Shah et al. (2018); Shahbazian et al. (2006); Shandilya et al. (2014); Sharma et al. (2011); Sharma et al. (2014); Shi and Sun (2015); Shi et al. (2008); Shih et al. (2012); Sinclair et al. (2006); Smith and Enquist (2002); Snyder et al. (2004); Stoilov et al. (2004); Stokoe et al. (1992); Su et al. (2001); Tacke et al. (1998); Tafforeau et al. (2011); Tan et al. (2004); Tan et al. (2012); Tanenbaum et al. (2006); Tantos et al. (2013); Tarakhovsky and Prinjha (2018); Tavares et al. (2015); Tee et al. (2002); Thaker et al. (2019); Thejer et al. (2020); Tiedje et al. (2015); Tokuyama et al. (2001); Toughiri et al. (2013); Trencia et al. (2003); Trigg and Ferguson (2015); Tsai and Seto (2002); Tsai et al. (1993); Tsoi et al. (2014); Tsvetkov and Stern (2005); Ui et al. (2015); Ujike and Taguchi (2015); Valvezan and Klein (2012); Vind et al. (2011); Vishwanatha and Kumble (1993); Wada et al. (2001); Walter et al. (2002); Walter et al. (2016); Wang and Prives (1995); Wang and Zhang (1999); Wang et al. (2000); Wang et al. (2007); Wang et al. (2008); Wang et al. (2013); Wang et al. (2020); Ward et al. (2004); Wen et al. (1995); Wertz et al. (2015); Willems et al. (1996); Williams et al. (1997); Wohlbold et al. (2012); Wolin and Cedervall (2002); Wortzel and Seger (2011); Wu et al. (2014); Wu et al. (2018); Wurm et al. (2001); Xu et al. (2011); Yang et al. (2012a); Yang et al. (2012b); Yang et al (2014); Yao et al. (2017); Ye et al. (2008); Yim et al. (2013); Yoo et al. (2019); Yu et al. (2009); Yu et al. (2011); Yu et al. (2012); Yui et al. (2001); Zhang et al. (1998); Zhang et al. (2009); Zhang et al. (2015); Zhang et al. (2019a); Zhang et al. (2019b); Zhao et al. (2015); Zhou et al. (2016); Zhu et al. (2001); Zhu et al. (2017); Zou et al. (2007); Zuo and Manley (1993). |
| T971 |
8226-8250 |
Sentence |
denotes |
Supplemental Information |
| T972 |
8251-8315 |
Sentence |
denotes |
Table S1 Phosphorylation and Abundance Data, Related to Figure 1 |
| T973 |
8316-8383 |
Sentence |
denotes |
Contains proteomic data of Vero E6 cells upon SARS-CoV-2 infection. |
| T974 |
8384-8689 |
Sentence |
denotes |
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). |
| T975 |
8690-8833 |
Sentence |
denotes |
Lastly, find the full list of unfiltered phosphorylation sites upon N protein overexpression in Vero E6 cells (PhosphoNOverexpressionFull tab). |
| T976 |
8834-8885 |
Sentence |
denotes |
Column descriptions are indicated in the final tab. |
| T977 |
8886-8943 |
Sentence |
denotes |
Table S2 Viral Phosphorylation Sites, Related to Figure 2 |
| T978 |
8944-9044 |
Sentence |
denotes |
List of phosphosites found on viral proteins from this study as well as from Davidson et al. (2020). |
| T979 |
9045-9098 |
Sentence |
denotes |
Table S3 Enrichments, Related to Figures 1, 4, and S1 |
| T980 |
9099-9385 |
Sentence |
denotes |
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). |
| T981 |
9386-9437 |
Sentence |
denotes |
Column descriptions are indicated in the final tab. |
| T982 |
9438-9495 |
Sentence |
denotes |
Table S4 Predicted Kinase Activities, Related to Figure 4 |
| T983 |
9496-9603 |
Sentence |
denotes |
Full results of predicted kinase activities for each time point post infection with SARS-CoV-2 (Kinase Act. |
| T984 |
9604-9666 |
Sentence |
denotes |
Viral Infection tab) and N protein overexpression (Kinase Act. |
| T985 |
9667-9689 |
Sentence |
denotes |
N Overexpression tab). |
| T986 |
9690-9907 |
Sentence |
denotes |
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. |
| T987 |
9908-9994 |
Sentence |
denotes |
Kinase activities possessing any absolute value change greater than 1.5 are indicated. |
| T988 |
9995-10046 |
Sentence |
denotes |
Column descriptions are indicated in the final tab. |
| T989 |
10047-10129 |
Sentence |
denotes |
Table S5 Prioritized Phosphorylation Site Review, Related to Figure 7 and Table S8 |
| T990 |
10130-10332 |
Sentence |
denotes |
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. |
| T991 |
10333-10339 |
Sentence |
denotes |
2020). |
| T992 |
10340-10489 |
Sentence |
denotes |
Includes literature context for prioritized phosphorylation sites, including their known functions and proposed relevance to SARS-CoV-2 pathogenesis. |
| T993 |
10490-10559 |
Sentence |
denotes |
Phosphorylation sites are partitioned into eight biological contexts. |
| T994 |
10560-10631 |
Sentence |
denotes |
Table S6 Predicted Transcription Factor Activities, Related to Figure 6 |
| T995 |
10632-10787 |
Sentence |
denotes |
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. |
| T996 |
10788-10830 |
Sentence |
denotes |
2020) using DoRothEA (Garcia-Alonso et al. |
| T997 |
10831-10837 |
Sentence |
denotes |
2019). |
| T998 |
10838-10892 |
Sentence |
denotes |
Gene symbols, NES scores, and cell lines are depicted. |
| T999 |
10893-10946 |
Sentence |
denotes |
Table S7 Cytokine Profiling Data, Related to Figure 6 |
| T1000 |
10947-11057 |
Sentence |
denotes |
Results from Luminex profiling of SARS-CoV-2 infected ACE2-A549 cells pre-treated with p38 inhibitor SB203580. |
| T1001 |
11058-11134 |
Sentence |
denotes |
Supernatants from infected cells were evaluated for 34 cytokines/chemokines. |
| T1002 |
11135-11151 |
Sentence |
denotes |
Units are pg/mL. |
| T1003 |
11152-11230 |
Sentence |
denotes |
Table S8 Drugs and Compounds, Related to Figures 7 and S5 and Tables S4 and S5 |
| T1004 |
11231-11343 |
Sentence |
denotes |
Drugs and compounds mapped to top kinase activities (Table S4) and prioritized phosphorylation sites (Table S5). |
| T1005 |
11344-11608 |
Sentence |
denotes |
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. |
| T1006 |
11609-11723 |
Sentence |
denotes |
FullDrugResponseData tab depicts mean and standard deviation for drug screening experiments depicted in Figure S5. |
| T1007 |
11725-11740 |
Sentence |
denotes |
Acknowledgments |
| T1008 |
11741-13493 |
Sentence |
denotes |
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. |
| T1009 |
13494-13571 |
Sentence |
denotes |
Hoffmann-La Roche and Vir Biotechnology and gifts from The Ron Conway Family. |
| T1010 |
13572-13637 |
Sentence |
denotes |
K.M.S. is an investigator of the Howard Hughes Medical Institute. |
| T1011 |
13638-13827 |
Sentence |
denotes |
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. |
| T1012 |
13828-13839 |
Sentence |
denotes |
Government. |
| T1013 |
13840-13947 |
Sentence |
denotes |
We would like to acknowledge Desiree Ho, Innovative Genomics Institute, for SARS-CoV-2 virus illustrations. |
| T1014 |
13948-14077 |
Sentence |
denotes |
We thank Randy Albert for support with the BSL3 facility and procedures at the Icahn School of Medicine at Mount Sinai, New York. |
| T1015 |
14079-14099 |
Sentence |
denotes |
Author Contributions |
| T1016 |
14100-14422 |
Sentence |
denotes |
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. |
| T1017 |
14423-14433 |
Sentence |
denotes |
Dunham, M. |
| T1018 |
14434-14561 |
Sentence |
denotes |
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. |
| T1019 |
14562-14572 |
Sentence |
denotes |
Dunham, M. |
| T1020 |
14573-14828 |
Sentence |
denotes |
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. |
| T1021 |
14829-14874 |
Sentence |
denotes |
Modak, J.B., A.R., T.P., Q.L., R.H., M.C., M. |
| T1022 |
14875-14951 |
Sentence |
denotes |
Muralidharan, M.K., G.J., B.T., J.H., D.L.S., and M.B.; RNA-seq Analysis, A. |
| T1023 |
14952-15301 |
Sentence |
denotes |
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. |
| T1024 |
15303-15327 |
Sentence |
denotes |
Declaration of Interests |
| T1025 |
15328-15409 |
Sentence |
denotes |
The Krogan laboratory has received research support from Vir Biotechnology and F. |
| T1026 |
15410-15428 |
Sentence |
denotes |
Hoffmann-La Roche. |
| T1027 |
15429-15531 |
Sentence |
denotes |
K.M.S. has consulting agreements for the following companies involving cash and/or stock compensation: |
| T1028 |
15532-15799 |
Sentence |
denotes |
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. |
| T1029 |
15800-15904 |
Sentence |
denotes |
Revolution Medicines (WDB002), Type6 Therapeutics, Venthera, and Wellspring Biosciences (Araxes Pharma). |
| T1030 |
15905-15996 |
Sentence |
denotes |
Supplemental Information can be found online at https://doi.org/10.1016/j.cell.2020.06.034. |
