REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Mouse Anti-GAPDH	Santa Cruz Biotechnology	Cat#sc-32233; RRID: AB_627679
Goat anti-Rabbit IgG-HRP	Southern Biotech	Cat#4030-05; RRID: AB_2687483
Goat anti-Mouse IgG-HRP	Southern Biotech	Cat#1031-05; RRID: AB_2794307
Goat anti-ACE2 IgG	R&D Systems	Cat#AF933; RRID: AB_355722
Rabbit anti-TMPRSS2 IgG	Abcam	Cat#ab92323; RRID: AB_10585592
Rabbit Anti-Goat IgG-HRP	R&D Systems	Cat#HAF017; RRID: AB_562588
Rabbit Anti-PIK3R4	Novus Biologicals	Cat#NBP1-30463; RRID: AB_2163632
Rabbit Anti-TMEM106B	Atlas Antibodies	Cat#HPA058342; RRID: AB_2683684
Mouse Anti-VAC14 (C-10)	Santa Cruz Biotechnology	Cat#sc-271831; RRID: AB_10709168
Bacterial and Virus Strains
HCoV-OC43	ATCC	Cat#VR-1558
HCoV-229E	ATCC	Cat#VR-740
SARS-CoV-2 (USA/WA-1/2020 strain)	BEI Resources	Cat#NR-52281
SARS-CoV-2 Reporter Virus Particles	Integral Molecular	Cat#RVP-701
SARS-CoV-2 Spike-Pseudotyped VSV-dG-GFP	This study	N/A
Stbl3 E.coli	Berkeley MacroLabs	N/A
Chemicals, Peptides, and Recombinant Proteins
Polybrene	Santa Cruz Biotechnology	Cat#SC134220
Puromycin Dihydrochloride	GIBCO	Cat#A1113803
Blasticitin S HCl	GIBCO	Cat#A1113903
Hygromycin B	Mirus Bio	Cat#MIR5930
TrypLE Express	GIBCO	Cat#12604013
SAR405	SelleckChem	Cat#S7682
YM201636	SelleckChem	Cat#S1219
PF-429242 dihydrochloride	Sigma	Cat#SML0667
Fatostatin HBr	SelleckChem	Cat#S8284
Bardoxolone	SelleckChem	Cat#S6647
25-Hydroxycholesterol	Sigma	Cat#H1015
Zeocin	InvivoGen	Cat#ant-zn-1
Critical Commercial Assays
KAPA HiFi HotStart ReadyMixPCR Kit	Kapa Biosciences	Cat#KK2602
QuickExtract	Lucigen	Cat#QE09050
Power SYBR Cells-to-CT kit	Invitrogen	Cat#44-029-55
NEBuilder HiFi DNA Assembly Master Mix	New England BioLabs	Cat#E2621L
FugeneHD	Promega	Cat#E2311
QIAamp DNA Blood Maxi Kit	QIAGEN	Cat#51194
Quick-DNA Midiprep Plus	Zymo	Cat#D4075
QIAquick PCR Purification kit	QIAGEN	Cat#28104
QIAquick Gel Extraction Kit	QIAGEN	Cat#28704
TransIT-X2	Mirus Bio	Cat#MIR6003
DNA/RNA Shield	Zymo	Cat#R1100-250
Quick-DNA/RNA Viral MagBead kit	Zymo	Cat#R2141
Luna Universal Probe One-Step RT-qPCR Kit	NEB	Cat#E3006E
Cell Titer Glo	Promega	Cat#G7570
Gibson Assembly master mix	NEB	Cat#E2611L
JetOptimus	Polyplus	Cat#117-07
QiaAmp virus RNA mini kit	QIAGEN	Cat#52906
SuperScript™ III One-Step RT-PCR System with Platinum™ Taq DNA Polymerase	Invitrogen	Cat#12574026
Deposited Data
Raw sequencing data for CRISPR KO screens	EMBL-EBI ArrayExpress	E-MTAB-9638
Tables S1, S2, S3, S4, and S5	Mendeley Data	https://dx.doi.org/10.17632/r49yg49ddc
Experimental Models: Cell Lines
Huh7.5.1	Zhong et al., 2005	N/A
HEK293FT	Thermo Scientific	Cat#R70007
Vero	ATCC	Cat#CCL-81
A549-ACE2	Gift from Olivier Schwartz	N/A
Calu-3	ATCC	Cat#HTB-55
VeroE6	ATCC	Cat#CRL-1586
Oligonucleotides
Primers for CRISPR screen library amplification, see Table S5	This study	N/A
Primers for cDNA cloning, see Table S5	This study	N/A
sgRNA sequences for clonal Huh7.5.1 KO cell generation, see Table S5	This study	N/A
Primers for genotyping of clonal Huh7.5.1 KO cells, see Table S5	This study	N/A
sgRNA sequences for RNP editing of A549-ACE2 cells, see Table S5	This study	N/A
Primers for genotyping of RNP-edited A549-ACE2 cells, see Table S5	This study	N/A
sgRNA sequences for Calu-3 KO cell generation, see Table S5	This study	N/A
qPCR primer and probe sequences, see Table S5	This study	N/A
Primers for VSVdG-CoV-2-S generation and sequencing, see Table S5	This study	N/A
Recombinant DNA
lentiCas9-Blast	Sanjana et al., 2014	Addgene Cat#52962
human GeCKO v2 library	Sanjana et al., 2014	Addgene Cat#1000000049
pX458	Ran et al., 2013	Addgene Cat#48138
hACE2	Li et al., 2003	Addgene Cat#1786
TMPRSS2	Edie et al., 2018	Addgene Cat#53887
TMEM106B	Genscript	Cat#OHu17671
VAC14	Lemaire and McPherson, 2006	Addgene Cat#47418
plenti-CMV-Puro-DEST	Campeau et al., 2009	Addgene Cat#17452
plenti-CMV-Hygro-DEST	Campeau et al., 2009	Addgene Cat#17454
pCMV-dR8.2 dvpr	Stewart et al., 2003	Addgene Cat#8455
pCMV-VSV-G	Stewart et al., 2003	Addgene Cat#8454
pAdVAntage	Promega	Cat#E1711
pLenti-DsRed_IRES_EGFP	Rousseaux et al., 2016	Addgene Cat#92194
PIK3R4	Johannessen et al., 2010	Addgene Cat#23488
VPS16	Jiang et al., 2014	Addgene Cat#67023
lentiCRISPRv2	Sanjana et al., 2014	Addgene Cat#52961
plenti-CMV-GFP-Zeo	Campeau et al., 2009	Addgene Cat#17449
pCAGEN	Matsuda and Cepko, 2004	Addgene Cat#11160
VSV-eGFP-dG	Beier et al., 2011	Addgene Cat#31842
SARS-CoV2-S codon optimized gBlocks, see Table S5	IDT	N/A
Software and Algorithms
MaGeCK	Li et al., 2014	https://sourceforge.net/p/mageck/wiki/Home
R 3.6.0	R	https://www.r-project.org
FlowJo 10.6.1	FlowJo LLC	N/A
ChemiDoc MP Imaging System	Bio-Rad	N/A
MATLAB R2020a	MathWorks	N/A
Cytoscape 3.8.0	Cytoscape	https://cytoscape.org
GraphPad Prism 8	GraphPad	N/A
Sequencher 5.1	Gene Codes	N/A
CFX Maestro™ Software	Bio-Rad	Cat #12004110