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).