REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Alexa fluor 647-mouse monoclonal anti-human CD326 (EpCAM) (clone 9C4)	BioLegend	Cat#324212, RRID: AB_756086
Mouse IgG2b, κ isotype control antibody	BioLegend	Cat#400301
Mouse monoclonal anti-HT2-280	Terrace Biotech	Cat#TB-27AHT2-280, RRID: AB_2832931
Alexa fluor 488-donkey anti-mouse IgM, μ chain specific	Jackson ImmunoResearch Laboratories	Cat#715-545-020, RRID: AB_2340844
Mouse monoclonal anti-SARS-CoV/SARS-CoV-2 nucleocapsid	Sino Biological	Cat#40143-MM05, RRID: AB_2827977
Mouse monoclonal anti-SARS-CoV-2 (COVID-19) spike (clone 1A9)	GeneTex	Cat#GTX632604, RRID: AB_2864418
Mouse monoclonal anti-SFTPB	Santa Cruz Biotechnology	Cat#sc133143, RRID: AB_2285686
Rabbit polyclonal anti-SFTPC	Millipore	Cat#AB3786, RRID: AB_91588
Rabbit monoclonal anti-AQP5	Abcam	Cat#ab92320, RRID: AB_2049171
Goat polyclonal anti-ACE2	R&D Systems	Cat#AF933, RRID: AB_355722
Donkey polyclonal anti-mouse IgG (H+L), Alexa Fluor 488	Thermo Fisher Scientific	Cat#A-21202, RRID: AB_141607
Donkey polyclonal anti-mouse IgG (H+L), Alexa Fluor 647	Thermo Fisher Scientific	Cat#A-31571, RRID: AB_162542
Donkey polyclonal anti-rabbit IgG (H+L), Alexa Fluor 568	Thermo Fisher Scientific	Cat#A10042, RRID: AB_2534017
Donkey polyclonal anti-goat IgG (H+L), Alexa Fluor 647	Thermo Fisher Scientific	Cat#A-21447, RRID: AB_141844
Goat anti-mouse IgG, colloidal gold (5 nm) conjugated	EY Laboratories	Cat#GAF-011-5
Bacterial and virus strains
SARS-CoV-2	This paper	JPN/Kanagawa/KUH003, DDBJ: LC630936
Chemicals, peptides, and recombinant proteins
Advanced DMEM/F12	Thermo Fisher Scientific	Cat#12634010
HEPES	Thermo Fisher Scientific	Cat#15630080
Penicillin-streptomycin	Thermo Fisher Scientific	Cat#15140122
GlutaMAX supplement	Thermo Fisher Scientific	Cat#35050061
Matrigel	Corning	Cat#356231
B-27 supplement	Thermo Fisher Scientific	Cat#17504044
N-Acetyl-L-cysteine	Sigma-Aldrich	Cat#A9165
[Leu15]-gastrin I human	Sigma-Aldrich	Cat#G9145
Afamin-Wnt-3A serum-free conditioned medium	Mihara et al., 2016	N/A
Recombinant human Wnt3A	R&D Systems	Cat#5036-WN
Recombinant human Wnt7B	Abnova	Cat#H00007477-P01
Recombinant mouse EGF	Thermo Fisher Scientific	Cat#PMG8043
Recombinant human IGF-1	BioLegend	Cat#590904
Recombinant human FGF-basic	Peprotech	Cat#100-18B
Recombinant human FGF10	Peprotech	Cat#100-26
Recombinant human KGF (FGF-7)	Peprotech	Cat#100-19
Recombinant human Epiregulin	BioLegend	Cat#550202
Recombinant human HB-EGF	Peprotech	Cat#100-47
Recombinant human neuregulin-1 (Heregulinβ-1)	Peprotech	Cat#100-03
Recombinant human HGF	Peprotech	Cat#100-39
Recombinant human IL-6	Peprotech	Cat#AF-200-06
Recombinant human SDF-1	Peprotech	Cat#300-28A
Recombinant human IL1-β	Peprotech	Cat#200-01B
Recombinant human TNF-α	Peprotech	Cat#300-01A
Wnt-C59	ShangHai Biochempartner	Cat#1243243-89-1
Recombinant mouse noggin	Peprotech	Cat#250-38
R-spondin-1 conditioned medium	Ootani et al., 2009	N/A
A83-01	Tocris	Cat#2939
SB202190	Sigma-Aldrich	Cat#S7067
Y-27632	FUJIFILM Wako Pure Chemical	Cat#253-00513
Fetal bovine serum	BioWest	Cat#S1820
Cell recovery solution	Corning	Cat#354253
Liberase TH research grade	Roche	Cat#05401151001
TrypLE Express	Thermo Fisher Scientific	Cat#12605010
Red Blood Cell Lysis Buffer	Roche	Cat#11814389001
Propidium Iodide	FUJIFILM Wako Pure Chemical	Cat# 169-26281
Hoechst 33342	Thermo Fisher Scientific	Cat#H3570
Puromycin	Thermo Fisher Scientific	Cat#A1113803
G418, Geneticin	Thermo Fisher Scientific	Cat#10131035
Lopinavir	Sigma-Aldrich	Cat#SML1222
Nelfinavir	Selleck	Cat#S4282
Remdesivir	Selleck	Cat#S8932
ProLong Diamond Antifade Mountant	Thermo Fisher Scientific	Cat#P36961
Power Block Universal Blocking Reagent	BioGenex	Cat#HK083-50K
BTXpress Solution	BTX	Cat#45-0805
Opti-MEM I Reduced Serum Medium	Thermo Fisher Scientific	Cat#31985062
Critical commercial assays
RNeasy Plus Mini Kit	QIAGEN	Cat#74134
Direct-zol RNA MicroPrep Kit	Zymo Research	Cat#R2061
TruSeq RNA Library Prep Kit v2	Ilumina	Cat#RS-122-2001
SARS-CoV-2 Detection Kit -N2 set-	TOYOBO	Cat#NCV-302
CellTiter-Glo	Promega	Cat#G9681
iPGell	GenoStaff	Cat#PG20-1
Deposited data
Raw RNA sequencing count data of alveolospheres and airway organoids	This paper	GEO: GSE171430
Raw RNA sequencing count data of mock-infected and SARS-CoV-2 infected alveolospheres	This paper	GEO: GSE171430
Experimental models: Cell lines
Human: alveolospheres: see Table S2	This paper	N/A
Human: airway organoids: see Table S2	This paper	N/A
Vero E6/TMPRSS2	Matsuyama et al., 2020	JCRB: JCRB1819
Recombinant DNA
PB-CMV-MCS-EF1a-GFP-Puro vector	System Biosciences	Cat#PB513B-1
Super PiggyBac Transposase Expression Vector	System Biosciences	Cat#PB200PA-1
Software and algorithms
R (version 3.6.0)	Comprehensive R Archive Network	https://cran.r-project.org/
cutadapt (version 1.18)	Martin, 2011	https://cutadapt.readthedocs.io/en/stable/installation.html
STAR (version 2.6.1b)	Dobin et al., 2013	https://github.com/alexdobin/STAR
RSEM (version 1.3.3)	Li and Dewey, 2011	https://github.com/deweylab/RSEM
R Bioconductor package DESeq2	Bioconductor, Love et al., 2014	http://bioconductor.org/packages/release/bioc/html/DESeq2.html
R Bioconductor package fgsea	Bioconductor, Korotkevich et al., 2019 (bioRxiv)	https://www.bioconductor.org/packages/release/bioc/html/fgsea.html
MSigDB v7.0	Broad Institute	https://www.gsea-msigdb.org/gsea/msigdb/index.jsp
LAS X	Leica Microsystems	https://www.leica-microsystems.com/products/microscope-software/
BZ-X analyzer	Keyence	N/A