REAGENT or RESOURCE SOURCE IDENTIFIER Antibodies Phospho-p38 MAPK (Thr180/Tyr182) Cell Signaling Cat#9211S ɑ-Rabbit IgG HRP Conjugate Biorad Cat#1706515 ɑ-Mouse IgG HRP Conjugate Biorad Cat#1706516 SARS-CoV-2 N (recombinant mouse monoclonal) Donated from the laboratory of Thomas Moran (Mount Sinai) N/A GAPDH Cell Signaling Cat#2118S Phospho-MAPKAPK2 (T334) Cell Signaling Cat#3007T Phospho-CREB/ATF-1 (S133) Cell Signaling Cat#9198S CK2α Abcam Cat#ab70774 SARS-CoV membrane (M) Rockland Cat#100-401-A55 SARS-CoV nucleocapsid (N) Rockland Cat#200-401-A50 AF568-labeled goat-anti-rabbit InvitrogenCat# Cat#A11011 AF647-labeled goat-anti-mouse Invitrogen Cat#A21235 AF488-labeled Phalloidin Hypermol Cat#8813-01 viral NP protein anti-sera produced in the Garcia-Sastre lab N/A Bacterial and Virus Strains SARS-CoV-2, isolate BetaCoV/France/IDF0372/2020 European Virus Archive goes Global (EVAg) IDF0372/2020 SARS-CoV-2, isolate USA-WA1/2020 BEI Resources Cat#NR-52281 SARS-CoV-2, Isolate Muc-IMB-1/2020 Bundeswehr Institute of Microbiology, Munich, Germany N/A Chemicals, Peptides, and Recombinant Proteins cOmplete protease inhibitor cocktail tablets mini, EDTA-free Roche Cat#11846170001 PhosStop phosphatase inhibitor cocktail tablets Roche Cat#4906837001 Sep-Pak C18 cartridge Waters Cat#WAT054955 Sequencing-grade modified trypsin Promega Cat#V5111 Fetal bovine serum (FBS) Thermo Fisher Scientific Cat#10082 DMEM Thermo Fisher Scientific Cat#MT10013CV Water, HPLC grade Sigma-Aldrich Cat#270733-4 L; CAS#7732-18-5 Ni-NTA Superflow beads QIAGEN Cat#30210 Igepal Sigma-Aldrich Cat#I3021; CAS#9002-93-1 Minimal Essential Media (MEM) Corning Cat#10-009-CV Opti-MEM Thermo Fisher Scientific Cat#31985062 Paraformaldehyde, 4% solution in PBS (PFA) Thermo Scientific Cat#MFCD00133991 Formalin Fisher Scientific Cat#SF100-20; CAS#50-00-0, 67-56-1, 7558-79-4, 10049-21-5, 7732-18-5 4′,6-diamidino-2-phenylindole (DAPI) Thermo Scientific Cat#62247 ReprosilPur 1.9 μm particles ESI SOURCE SOLUTIONS Cat#R119 Crystal Violet Solution Sigma Aldrich Cat#HT90132-1L Thermanox coverslips Ted Pella Cat#26028 Silicon Chips Ted Pella Cat#16007 Aluminum specimen mounts Ted Pella Cat#16111 Double-sided carbon tape Ted Pella Cat#16084-1 Karnovsky’s EM fixative Electron Microscopy Sciences Cat#15720 Sodium Cacodylate Sigma Cat#C4945-10G; CAS#6131-99-3 Osmium Tetroxide Electron Microscopy Sciences Cat#19190; CAS#20816-12-0 Potassium Ferrocyanide Sigma Cat#P-3289; CAS#14459-95-1 Uranyl Acetate Ted Pella Cat#19481; CAS#6159-44-0 Spurr’s resin Ted Pella Cat#18300-4221 Iridium target Electron Microscopy Sciences Cat#3431 PolyJet SignaGen Cat#SL100688 SuperScript IV Reverse Transcriptase Invitrogen Cat#18090010 ARRY-371797 (ARRY-797) MedKoo Biosciences Cat#555466; CAS#1036404-17-7 Dilmapimod (SB-681323) MedChemExpress Cat#HY-10404; CAS#444606-18-2 Doramapimod (BIRB-796) SelleckChem Cat#S1574; CAS#285983-48-4 Losmapimod SelleckChem Cat#S7215; CAS#585543-15-3 MAPK13-IN-1 MedChemExpress Cat#HY-18850; CAS#229002-10-2 Neflamapimod (VX-745) SelleckChem Cat#S1458; CAS#209410-46-8 P38 MAPK Inhibitor (4) Cayman Chemical Cat#22219; CAS#1638-41-1 PF-3644022 Tocris Bioscience Cat#4483; CAS#142557-61-7 PH-797804 SelleckChem Cat#S2726; CAS#586379-66-0 Ralimetinib (LY2228820) SelleckChem Cat#S1494; CAS#862507-23-1 SB203580 SelleckChem Cat#S1076; CAS#152121-47-6 TAK-715 SelleckChem Cat#S2928; CAS#303162-79-0 Talmapimod (SCIO-469) MedChemExpress Cat#HY-10406; CAS#309913-83-5 VX-702 SelleckChem Cat#S6005; CAS#745833-23-2 4EGI-1 SelleckChem Cat#S7369; CAS#315706-13-9 A-484954 Tocris Bioscience Cat#4279; CAS#1276121-88-0 Abemaciclib mesylate SelleckChem Cat#S7158; CAS#1231930-82-7 Alisertib SelleckChem Cat#S1133; CAS#1028486-01-2 Apilimod SelleckChem Cat#S6414; CAS#541550-19-0 AT-13148 SelleckChem Cat#S7563; CAS#1056901-62-2 AZD-1208 SelleckChem Cat#S7104; CAS#1204144-28-4 AZD-5363 (Capivasertib) SelleckChem Cat#S8019; CAS#1143532-39-1 AZD-7648 SelleckChem Cat#S8843; CAS#2230820-11-6 Bafetinib SelleckChem Cat#S1369; CAS#859212-16-1 BMS-582949 SelleckChem Cat#S8124; CAS#623152-17-0 Bortezomib (PS-341) SelleckChem Cat#S1013; CAS#179324-69-7 CHIR-98014 SelleckChem Cat#S2745; CAS#252935-94-7 Dabrafenib (GSK2118436) SelleckChem Cat#S2807; CAS#1195765-45-7 Dasatinib SelleckChem Cat#S1021; CAS#302962-49-8 Dinaciclib SelleckChem Cat#S2768; CAS#779353-01-4 Dorsomorphin 2HCl SelleckChem Cat#S7306; CAS#1219168-18-9 EHT 1864 2HCl SelleckChem Cat#S7482; CAS#754240-09-0 Enzastaurin SelleckChem Cat#S1055; CAS#170364-57-5 Fludarabine SelleckChem Cat#S1491; CAS#S1491 Fosbretabulin (Combretastatin A4 Phosphate (CA4P)) Disodium SelleckChem Cat#S7204; CAS#168555-66-6 Ganetespib SelleckChem Cat#S1159; CAS#888216-25-9 Gilteritinib SelleckChem Cat#S7754; CAS#1254053-43-4 Idarubicin HCl SelleckChem Cat#S1228; CAS#57852-57-0 Ipatasertib SelleckChem Cat#S2808; CAS#1001264-89-6 Ispinesib (SB-715992) SelleckChem Cat#S1452; CAS#336113-53-2 Ixazomib (MLN2238) SelleckChem Cat#S2180; CAS#1072833-77-2 K-252a Cayman Chemical Cat#11338; CAS#99533-80-9 KenPaullone SelleckChem Cat#S7917; CAS#142273-20-9 KW-2449 SelleckChem Cat#S2158; CAS#1000669-72-6 LJI308 SelleckChem Cat#S7871; CAS#1627709-94-7 LMK-235 SelleckChem Cat#S7569; CAS#1418033-25-6 LY2584702 Tosylate SelleckChem Cat#S7704; CAS#1082949-68-5 MBQ-167 SelleckChem Cat#S8749; CAS#2097938-73-1 Mdivi-1 SelleckChem Cat#S7162; CAS#338967-87-6 Midostaurin SelleckChem Cat#S8064; CAS#120685-11-2 MK-2206 2HCl SelleckChem Cat#S1078; CAS#1032350-13-2 ML141 SelleckChem Cat#S7686; CAS#71203-35-5 NSC319276 SelleckChem Cat#S7149; CAS#71555-25-4 NVP-BEP800 SelleckChem Cat#S1498; CAS#847559-80-2 Palbociclib (PD-0332991) HCl SelleckChem Cat#S1116; CAS#827022-32-2 PF-03814735 SelleckChem Cat#S2725; CAS#942487-16-3 PF-3758309 SelleckChem Cat#S7094; CAS#898044-15-0 PHA-793887 SelleckChem Cat#S1487; CAS#718630-59-2 Pictilisib SelleckChem Cat#S1065; CAS#957054-30-7 PKR Inhibitor Cayman Chemical Cat#15323; CAS#608512-97-6 QNZ (EVP4593) SelleckChem Cat#S4902; CAS#545380-34-5 R-406 SelleckChem Cat#S2194; CAS#841290-81-1 R-547 SelleckChem Cat#S2688; CAS#741713-40-6 Rapamycin SelleckChem Cat#S1039; CAS#53123-88-9 Ravoxertinib SelleckChem Cat#S7554; CAS#1453848-26-4 Remdesivir BioVision Cat#B2997; CAS#1809249-37-3 Ripasudil (K-115) hydrochloride dihydrate SelleckChem Cat#S7995; CAS#887375-67-9 Romidepsin (FK228, Depsipeptide) SelleckChem Cat#S3020; CAS#128517-07-7 Ruboxistaurin HCl(LY333531) SelleckChem Cat#S7663; CAS#169939-93-9 Sapanisertib SelleckChem Cat#S2811; CAS#1224844-38-5 SAR-407899 Cayman Chemical Cat#21717; CAS#923359-38-0 SB743921 HCl SelleckChem Cat#S2182; CAS#940929-33-9 SGI-1776 free base SelleckChem Cat#S2198; CAS#1025065-69-3 Silmitasertib SelleckChem Cat#S2248; CAS#1009820-21-6 Sorafenib Tosylate SelleckChem Cat#S1040; CAS#475207-59-1 Sotrastaurin SelleckChem Cat#S2791; CAS#425637-18-9 Stattic SelleckChem Cat#S7024; CAS#19983-44-9 Staurosporine SelleckChem Cat#S1421; CAS#62996-74-1 Tanzisertib SelleckChem Cat#S8490; CAS#899805-25-5(freebase) Tasquinimod SelleckChem Cat#S7617; CAS#254964-60-8 THZ1 2HCl SelleckChem Cat#S7549; CAS#1604810-83-4(freebase) Tpl2 Kinase Inhibitor 1 Cayman Chemical Cat#19710; CAS#871307-18-5 U73122 SelleckChem Cat#S8011; CAS#112648-68-7 Volasertib SelleckChem Cat#S2235; CAS#755038-65-4 XL413 (BMS-863233) SelleckChem Cat#S7547; CAS#1169562-71-3 Y-39983 HCl SelleckChem Cat#S7935; CAS#173897-44-4 CCL2/MCP-1, Capture Antibody R&D Systems Cat#MAB679 CCL5/RANTES, Capture Antibody R&D Systems Cat#MAB678 CCL11/Eotaxin, Capture Antibody R&D Systems Cat#MAB320 GM-CSF, Capture Antibody R&D Systems Cat#MAB615 IL-1RA, Capture Antibody Peprotech Cat#500-P209 CCL13/MCP-4, Capture Antibody R&D Systems Cat#MAB327 IL-4, Capture Antibody R&D Systems Cat#MAB604 IL-10, Capture Antibody Peprotech Cat#500-P20 IL-15, Capture Antibody R&D Systems Cat#MAB647 IL-1beta, Capture Antibody R&D Systems Cat#MAB601 CCL8/MCP-2, Capture Antibody Peprotech Cat#500-P35 CXCL9/MIG, Capture Antibody Peprotech Cat#500-P50 CCL3/MIP-1alpha, Capture Antibody R&D Systems Cat#MAB670 CXCL2/GRO-Beta, Capture Antibody Peprotech Cat#500-P104 TGF-Beta1, Capture Antibody R&D Systems Cat#MAB240 CXCL16, Capture Antibody Peprotech Cat#500-P200 CXCL8/IL-8, Capture Antibody R&D Systems Cat#MAB208 MMP-9, Capture Antibody R&D Systems Cat#MAB936 CXCL1/GRO-alpha, Capture Antibody Peprotech Cat#500-P92 IL-7, Capture Antibody R&D Systems Cat#MAB207 CCL4/MIP-1beta, Capture Antibody R&D Systems Cat#MAB271 IL-1alpha, Capture Antibody R&D Systems Cat#MAB200 IL-12 (p70), Capture Antibody Peprotech Cat#500-P154G IL-16, Capture Antibody R&D Systems Cat#MAB316 CCL20/MIP-3a, Capture Antibody R&D Systems Cat#MAB360 TNF-alpha, Capture Antibody R&D Systems Cat#MAB610 Trappin-2/Elafin, Capture Antibody R&D Systems Cat#AF1747 IL-17A, Capture Antibody R&D Systems Cat#MAB317 CXCL10/IP-10, Capture Antibody R&D Systems Cat#MAB266 S100A8, Capture Antibody R&D Systems Cat#DS8900 IL-22, Capture Antibody Peprotech Cat#500-P211 CXCL5/ENA-78, Capture Antibody R&D Systems Cat#MAB654 IL-6, Capture Antibody R&D Systems Cat#MAB206 CCL7/MCP-3, Capture Antibody R&D Systems Cat#MAB282 CCL2/MCP-1, Protein std R&D Systems Cat#279-MC CCL5/RANTES, Protein std R&D Systems Cat#278-RN CCL11/Eotaxin, Protein std Peprotech Cat#300-21 GM-CSF, Protein std R&D Systems Cat#215-GM IL-1RA, Protein std Peprotech Cat#200-01RA CCL13/MCP-4, Protein std R&D Systems Cat#327-P4 IL-4, Protein std R&D Systems Cat#204-IL IL-10, Protein std Peprotech Cat#200-10 IL-15, Protein std R&D Systems Cat#247-ILB IL-1beta, Protein std R&D Systems Cat#201-LB CCL8/MCP-2, Protein std Peprotech Cat#300-15 CXCL9/MIG, Protein std R&D Systems Cat#392-MG CCL3/MIP-1alpha, Protein std R&D Systems Cat#270-LD CXCL2/GRO-Beta, Protein std Peprotech Cat#300-39 TGF-Beta1, Protein std Peprotech Cat#100-21 CXCL16, Protein std Peprotech Cat#300-55 CXCL8/IL-8, Protein std R&D Systems Cat#208-IL MMP-9, Protein std R&D Systems Cat#911-MP CXCL1/GRO-alpha, Protein std Peprotech Cat#300-11 IL-7, Protein std R&D Systems Cat#207-IL CCL4/MIP-1beta, Protein std R&D Systems Cat#271-BME IL-1alpha, Protein std Peprotech Cat#200-01A IL-12(p70), Protein std R&D Systems Cat#219-IL IL-16, Protein std Peprotech Cat#200-16 CCL20/MIP-3a, Protein std Peprotech Cat#300-29A TNF-alpha, Protein std R&D Systems Cat#210-TA Trappin-2/Elafin, Protein std R&D Systems Cat#1747-PI IL-17A, Protein std Peprotech Cat#200-17 CXCL10/IP-10, Protein std R&D Systems Cat#266-IP S100A8, Protein std R&D Systems Cat#DS8900 IL-22, Protein std Peprotech Cat#200-22 CXCL5/ENA-78, Protein std R&D Systems Cat#254-XB IL-6, Protein std R&D Systems Cat#206-IL CCL7/MCP-3, Protein std R&D Systems Cat#282-P3 CCL2/MCP-1, Detection Antibody R&D Systems Cat#BAF279 CCL5/RANTES, Detection Antibody R&D Systems Cat#BAF278 CCL11/Eotaxin, Detection Antibody R&D Systems Cat#BAF320 GM-CSF, Detection Antibody R&D Systems Cat#BAM 215 IL-1RA, Detection Antibody Peprotech Cat#500-P209BT CCL13/MCP-4, Detection Antibody R&D Systems Cat#BAF327 IL-4, Detection Antibody R&D Systems Cat#BAF204 IL-10, Detection Antibody Peprotech Cat#500-P20BT IL-15, Detection Antibody R&D Systems Cat#BAM 247 IL-1beta, Detection Antibody R&D Systems Cat#BAF201 CCL8/MCP-2, Detection Antibody Peprotech Cat#500-P35BT CXCL9/MIG, Detection Antibody Peprotech Cat#500-P50BT CCL3/MIP-1alpha, Detection Antibody R&D Systems Cat#BAF270 CXCL2/GRO-Beta, Detection Antibody Peprotech Cat#500P104BT TGF-Beta1, Detection Antibody R&D Systems Cat#BAM 2462 CXCL16, Detection Antibody Peprotech Cat#500-P200BT CXCL8/IL-8, Detection Antibody R&D Systems Cat#BAF208 MMP-9, Detection Antibody R&D Systems Cat#BAF911 CXCL1/GRO-alpha, Detection Antibody Peprotech Cat#500P92BT IL-7, Detection Antibody R&D Systems Cat#BAF207 CCL4/MIP-1beta, Detection Antibody R&D Systems Cat#BAF271 IL-1alpha, Detection Antibody R&D Systems Cat#BAF200 IL-12(p70), Detection Antibody Peprotech Cat#500-P154GBT IL-16, Detection Antibody R&D Systems Cat#BAF316 CCL20/MIP-3a, Detection Antibody R&D Systems Cat#BAF360 TNF-alpha, Detection Antibody R&D Systems Cat#BAF210 Trappin-2/Elafin, Detection Antibody R&D Systems Cat#BAF1747 IL-17A, Detection Antibody R&D Systems Cat#BAF317 CXCL10/IP-10, Detection Antibody Peprotech Cat#500-P93BT S100A8, Detection Antibody R&D Systems Cat#DS8900 IL-22, Detection Antibody Peprotech Cat#500-P211BT CXCL5/ENA-78, Detection Antibody R&D Systems Cat#BAF254 IL-6, Detection Antibody R&D Systems Cat#BAF206 CCL7/MCP-3, Detection Antibody R&D Systems Cat#BAF282 Critical Commercial Assays MTT assay Roche Cat#11465007001 Luna Universal One-Step RT-qPCR Kit New England Biolabs Cat#E3005L CellTiter-Glo Luminescent Cell Viability Assay Promega Cat#G7570 Direct-zol RNA Miniprep Plus kit Zymo Research Cat#R2072 KAPA SYBR FAST qPCR Master Mix Roche Cat#07959389001 Bio-Rad II Protein Assay Kit Bio-Rad Cat#5000002 Deposited Data Phosphoproteomics data of SARS-CoV-2 infected Vero E6 cells This paper PRIDE Project ID: PXD019113 Supplemental Tables in Mendeley Data This paper https://dx.doi.org/10.17632/dpkbh2g9hy.1 CORUM v3.0 Giurgiu et al., 2019 http://mips.helmholtz-muenchen.de/corum/ RNA-seq dataset for transcription factor activities Blanco-Melo et al., 2020 GSE147507 Phosphoproteomics datasets of biological conditions Ochoa et al., 2016 https://www.embopress.org/doi/full/10.15252/msb.20167295 Functional scores for phosphorylation sites Ochoa et al., 2020 https://idp.nature.com/authorize?response_type=cookie&client_id=grover&redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41587-019-0344-3 Gene identifier mapping database from BioMart Ensembl http://uswest.ensembl.org/biomart/martview/5ccd994c794265409f21c6194730ce5b Molecular Signatures Database for gene set enrichment analysis Subramanian et al., 2005 https://www.gsea-msigdb.org/gsea/msigdb/index.jsp Kinase-substrate relationships Bachman et al., 2019 https://www.biorxiv.org/content/10.1101/822668v3.full Chlorocebus proteome sequences for peptide searches Uniprot https://www.uniprot.org/proteomes/UP000029965 Sars-CoV-2 genomic sequences (hCoV-19/France/IDF0372/2020) GISAID Accession number EPI_ISL_406596 Experimental Models: Cell Lines ACE2-A549 human lung carcinoma Donated from the laboratory of Brad Rosenberg N/A Caco-2 ATCC Cat#HTB-37 VERO C1008 [Vero 76, clone E6, Vero E6] (Vero E6) ATCC Cat#CRL-1586 HEK293T/17 cells ATCC Cat#CRL-11268 Oligonucleotides ON-TARGETplus Human MAPK12 (6300) siRNA - SMARTpool, 5 nmol Horizon Discovery/Dharmacon Cat#L-003590-00-0005 ON-TARGETplus Human MAPK13 (5603) siRNA - SMARTpool, 5 nmol Horizon Discovery/Dharmacon Cat#L-003591-00-0005 ON-TARGETplus Human MAP2K3 (5606) siRNA - SMARTpool, 5 nmol Horizon Discovery/Dharmacon Cat#L-003509-00-0005 ON-TARGETplus Human ACE2 (59272) siRNA - SMARTpool Horizon Discovery/Dharmacon Cat#L-005755-00-0005 N gene region (reverse) 5′-CGAAGGTGTGACTTCCATG-3′ Eurofins N/A N gene region (forward)5′-TAATCAGACAAGGAACTGATTA-3′ Eurofins N/A Recombinant DNA pLVX-TetOne-Puro empty vector Takara Cat#631847 pLVX-TetOne-Puro-SARS-CoV-2-N-2xStrep This paper N/A pMD2.G, Addgene Gift from Didier Trono Addgene Plasmid #12259 Gag-Pol-Tat-Rev packaging construct Gift from Judd Hultquist pJH045 Software and Algorithms artMS Bioconductor https://www.bioconductor.org/packages/release/bioc/html/artMS.html MSstats Bioconductor https://www.bioconductor.org/packages/release/bioc/html/artMS.html The R Project for Statistical Computing R Core Team, 2019 http://www.r-project.org/index.html Spectronaut Biognosys https://biognosys.com/shop/spectronaut ZEN (Blue edition) Carl Zeiss Microscopy https://www.zeiss.com/zen SPPIDER v2 Porollo and Meller, 2007 http://sppider.cchmc.org/ DoRothEA Garcia-Alonso et al., 2019 https://saezlab.github.io/dorothea/ VIPER Alvarez et al., 2016 https://www.bioconductor.org/packages/release/bioc/html/viper.html Biostrings Bioconductor https://bioconductor.org/packages/release/bioc/html/Biostrings.html clusterProfiler Bioconductor https://bioconductor.org/packages/release/bioc/html/clusterProfiler.html DESeq2 package Love et al., 2014 http://bioconductor.org/packages/release/bioc/html/DESeq2.html Imaris 64x 9.5.1 Oxford Instruments https://imaris.oxinst.com/ MetaMorph (Version 7.8) Molecular Devices https://www.moleculardevices.com/ Other Orbitrap Exploris 480 MS with internal calibration option Thermo Fisher Scientific Cat#BRE725533 ZEISS LSM 800 Confocal Laser Scanning Microscope Carl Zeiss Microscopy Model#ZEISS LSM 800 QuantStudio 6 Real-Time PCR System Applied Biosystems Cat#4485697 FACSymphony BD Life Sciences N/A Infinity 2000 Plate Reader Tecan N/A Luminex MAGPIX platform Luminex Corp N/A LightCycler 480 Instrument II Roche N/A Bal-Tec Drier Balzers, Liechtenstein Cat#CPD 030 Quorum sputter coater Electron Microscopy Sciences, Hatfield, PA Cat#EMS300T D Hitachi field emission scanning electron microscope Hitachi, Tokyo, Japan Model#SU-8000 Leica UC7 ultramicrotome Leica Microsystems N/A FEI BT Tecnai transmission electron microscope Thermofisher/FEI N/A Gatan Rio camera Gatan N/A Celigo imaging cytometer Nexcelcom N/A