REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Anti-ANO6 antibody	This study	Epitope from Yang et al., 2012
Anti-SARS-CoV/SARS-CoV-2 (COVID-19) spike antibody [1A9]	GeneTex	Cat#GTX632604; RRID: AB_2864418
Anti-Aldolase A (C-10)	Santa Cruz	Cat#SC-390733
Anti-HIV-p24 antibody	GeneTex	Cat#GTX64128
Chemicals, peptides, and recombinant proteins
Dulbecco’s modified Eagle’s medium-high glucose	Gibco	Cat#11995-065
DMEM/Ham's F-12 (1:1) medium	WELGENE	Cat#LM 001-05, Cat#LM 010-02
L-glutamine	WELGENE	Cat#LS 002-01
Fetal Bovine Serum (FBS)	Gibco	Cat#26140-079
Penicillin-streptomycin	Gibco	Cat#15140122
RPMI 1640 with L-Glutamine	Capricorn Scientific	RPMI-A
Opti-MEM™ Reduced Serum Medium	Gibco	Cat#31985-070
Minimum Essential Medium (MEM) with Earle’s Balanced Salts containing 2.2 g/L sodium bicarbonate	HyClone	Cat#SH30024.01
Fetal Bovine Serum (FBS)	HyClone	Cat#SH30084.03
Penicillin-streptomycin	HyClone	Cat#SV300010
Poly-D-lysine Hydrobromide	Sigma-Aldrich	Cat#P6407
8-well Cell Culture Chamber slide	SPL Life Science	Cat#30108
BEBM™ Bronchial Epithelial Cell Growth Basal Medium	Lonza	Cat#CC-3171
Dulbecco’s Modified Eagle Medium (DMEM) with 1.0 g/L glucose and without L-Glutamine	Lonza	Cat#12-707F
BEGM™ Bronchial Epithelial Cell Growth Medium SingleQuots™ Supplements and Growth Factors	Lonza	Cat#CC-4175
Bovine Serum Albumin	Sigma-Aldrich	Cat#A7030-50G
12mm Transwell® with 0.45μm Pore Polyester Membrane Insert, Sterile	Corning	Cat#3460
Costar® 12-well Clear TC-treated Multiple Well Plates, Individually Wrapped, Sterile	Corning	Cat#3513
SmartTM library	Chemdiv	Cat#903OTP09
1,700 approved drugs	TargetMol	Cat#L1000
A6-001	Chemdiv	Cat#F575-0482
A6-004	Chemdiv	Cat#F474-2423
Fluo-4 NW	Invitrogen	Cat#F36206
Ionomycin	Alomone Labs	Cat#I-700
Cisplatin	Tokyo chemical industry	Cat#D3371
Amphotericin B solution	Sigma-Aldrich	Cat#A2942
Fura-2 AM	Invitrogen	Cat#F1201
cOmplete™, Mini, EDTA-free Protease Inhibitor Cocktail	Sigma-Aldrich, Roche	Cat#04693159001
IPTG	Duchefa	Cat#I1401.0025
Ni-NTA protein purification system	QIAGEN	Cat#30230
Formaldehyde solution for molecular biology, 36.5–38% in H2O	Sigma-Aldrich	Cat#F8775
Paraformaldehyde	Biosesang	Cat#PC2031-050-00
Triton X-100	Biosesang	Cat#T1020
Bovine Serum Albumin	Millipore	Cat#82-100-6
Alexa Fluor 488 Phalloidin	Invitrogen	Cat#A12379
DAPI	Sigma-Aldrich	Cat#D9542
Fluorescence Mounting Medium	Dako	Cat#S3023
VECTASHIELD mounting medium with DAPI	Vector Laboratories	Cat#H-1500
TransIT-X2 Dynamic Delivery System	Mirus Bio LLC	Cat#MIR6006
Polybrene	Merck-Millipore	Cat#TR-1003-G
Blasticidin S HCl	Gibco	Cat#A1113903
Puromycin dihydrochloride	Gibco	Cat#A1113803
Hygromycin B	Invitrogen	Cat#10687010
Abamectin	Cayman Chemical	Cat#19201
Ivermectin	Sigma-Aldrich	Cat#I8898
Camostat mesylate	Sigma-Aldrich	Cat#SML0057
BAPTA-AM	Sigma-Aldrich	Cat#A1076
Trypsin from porcine pancreas	Sigma-Aldrich	Cat#T6567
SeaPlaque™ Agarose	Lonza	Cat#50101
Neutral Red Solution	Sigma-Aldrich	Cat#2889
(2-Hydroxypropyl)-beta-cyclodextrin	Sigma-Aldrich	Cat#H107-5G
Lipofectamine® 2000	Invitrogen	Cat#11668-019
16:0-06:0 NBD PS	Avanti Polar Lipids	Cat# 810192
Lenti-X™ Concentrator	Clontech Laboratories	Cat#631232
Vybrant™ DiO Cell-Labeling Solution	Invitrogen	Cat#V22886
Propidium Iodide	Abcam	Cat#ab14083
Critical commercial assays
BioFACT™ Pfu DNA Polymerase	BioFACT	Cat#PD116-250
BioFACT™ Taq DNA Polymerase	BioFACT	Cat#ST116-500
NEBuilder® HiFi DNA Assembly Master Mix	NEB Biolabs	Cat#E2621
Tri-RNA reagent	Favorgen Biotech	Cat#FATRR 001
RNA to cDNA EcoDry Premix	Takara Bio	Cat#639549
TB Green™ Premix Ex Taq™ (Tli RNaseH Plus)	Takara Bio	Cat#RR420L
Pierce™ BCA Protein Assay Kit	Thermo Scientific	Cat#23227
CellTiter 96® AQueous One Solution Cell Proliferation Assay kit	Promega	Cat#G3581
Cell counting kit-8	Dojindo Molecular Technologies Inc.	Cat#CK04
QIAamp Viral RNA Mini kit	QIAGEN	Cat#52906
QIAamp DNA mini kit	QIAGEN	Cat#51304
Luna® Universal One-Step RT-qPCR Kit	NEW ENGLAND BioLabs®Inc	Cat#E3006E
Luciferase assay system	Promega	Cat#E1501
KAPA SYBR FAST qPCR Kits	Sigma-Aldrich	Cat#KK4605
Experimental models: Cell lines
CHO-K1	ATCC	CCL-61
HeLa	ATCC	CCL-2
HEK293T	ATCC	CRL-3216
HeLa-ACE2	This study	N/A
FRT-YFP(H148Q/I152L/F46L)-ANO1	This study	N/A
FRT-YFP(H148Q/I152L/F46L)-ANO2	This study	N/A
FRT-YFP(H148Q/I152L/F46L)-ANO6	This study	N/A
Vero	Ministry of Food and Drug Safety, Republic of Korea	VERO01WCB-1201
Calu-3	Korean Cell Line Bank	KCLB #30055
HEK293T-ACE2-TMPRSS2 (mCherry-expressing)	Genecopoeia	Cat#SL222
Human nasal epithelial (HNE) cells	This study	N/A
Jurkat	Korean Cell Line Bank	KCLB #40152
Experimental models: Bacterial and virus strains
HIT Competent Cells-BL21(DE3) strains (Value 107)	RBC	Cat#RH217
HIT Competent Cells-DH5 alpha strains (Value 108)	RBC	Cat#RH617
Lentifect™ SARS-CoV-2 ER retention signal removed Spike-pseudotyped Lentivirus	Genecopoeia	Cat#SP001
SARS-CoV-2 (BetaCoV/korea/KUMC-2)	Clinical isolate	GISAID accession#: EPI_ISL_413018
Recombinant eGFP adenovirus (Ad-eGFP)	Vector Biolabs	Cat#1060
Oligonucleotides
AccuTargetTM pre-designed human TMEM16F-specific siRNA : 5′-GAG AAC AGC CUC ACC AUG A-3′ and 5′-UCA UGG UGA GGC UGU UCU C-3′	Bioneer	196527-1
AccuTargetTM pre-designed human TMEM16F-specific siRNA : 5′-CAG CUU UCC CAC UCC AUG A-3′ and 5′-UCA UGG AGU GGG AAA GCU G-3′	Bioneer	196527-2
AccuTargetTM pre-designed human TMEM16F-specific siRNA: 5′-CAC GAU GUA CUC ACG UAG U-3′ and 5′-ACU ACG UGA GUA CAU CGU G-3′	Bioneer	196527-3
hGAPDH qPCR forward primer: 5′-AAT CCC ATC ACC ATC TTC CA-3′	This study	N/A
hGAPDH qPCR reverse primer: 5′-TGG ACT CCA CGA CGT ACT CA-3′	This study	N/A
hTMEM16A qPCR forward primer: 5′-AGA GGA GGC TGT CAA GGA TCA-3′	This study	N/A
hTMEM16A qPCR reverse primer: 5′- ATA TGC CGG CGC TTC TCT TT -3′	This study	N/A
hTMEM16F qPCR forward primer: 5′-AGA AAA GAT AAC CCC ACG AT-3′	This paper	N/A
hTMEM16F qPCR reverse primer: 5′-GAC GAA CCC AAA CTG AAT AA-3′	This paper	N/A
SARS-CoV-2 nsp targeting forward primer: 5′- TGG GGY TTT ACR GGT AAC CT-3′	Chu et al., 2020	N/A
SARS-CoV-2 nsp targeting reverse primer: 5′- AAC RCG CTT AAC AAA GCA CTC -3′	Chu et al., 2020	N/A
probe 5′-56-FAM- TAGTTGTGA/ ZEN/TGCWATCATGACTAG-3IABkFQ-3′	Chu et al., 2020	N/A
(Ad-)eGFP qPCR forward primer: 5′-AGT CCG CCC TGA GCA AAG A	SignaGen® Laboratories	N/A
(Ad-)eGFP qPCR reverse primer: 5′- TCC AGC AGG ACC ATG TGA TC	SignaGen® Laboratories	N/A
Recombinant DNA
Plasmid: pcDNA3.1-ANO6(V5)	Lin et al., 2019	N/A
Plasmid: pcDNA3.1-hACE2	Addgene	#145033
Plasmid: pcDNA3.1-SARS2-Spike	Addgene	#145032
Plasmid: pcDNA3.1-SARS2-Spike-R682SR685G	This study	Modified from Addgene #145032
Plasmid: lentiCas9-Blast	Addgene	#52962
Plasmid: pLV-mcherry	Addgene	#36084
Plasmid: psPAX2	Addgene	#12260
Plasmid: pMD2.G	Addgene	#12259
Plasmid: Lact-C2-GFP	Addgene	#22852
Plasmid: pET28c(+)	Novagen	#69866
Software and algorithms
SnapGene (Version 2.3.2)	Snapgene	N/A
Primer Blast (A tool for finding specific primers)	NCBI	https://www.ncbi.nlm.nih.gov/tools/primer-blast/
MetaFluor	Molecular Devices	https://www.moleculardevices.com/products/cellular-imaging-systems/acquisition-and-analysis-software/metamorph-microscopy
Meta Morph microscopy analysis software (version 7.1)	Molecular Devices	https://www.moleculardevices.com/
pCLAMP software v.10.7	Molecular Devices	https://www.moleculardevices.com/products/axon-patch-clamp-system/acquisition-and-analysis-software/pclamp-software-suite#gref
Digidata-1440A	Molecular Devices	https://www.moleculardevices.com/products/axon-patch-clamp-system
Clampfit v. 10.7	Molecular Devices	https://www.moleculardevices.com/products/axon-patch-clamp-system
Origin v. 8.0	Origin Lab Inc.	https://www.originlab.com/index.aspx?go=PRODUCTS/Origin
Python3	Python Software Foundation	https://www.python.org/downloads/
OpenCV	Open Source Computer Vision Library	https://opencv.org/
NIS-elements AR	Nikon
ZEN 2012 black (2012 version)	Carl Zeiss	https://www.zeiss.com/microscopy/
Graph Pad Prism (version 8)	Graph Pad Software	https://www.graphpad.com/scientific-software/prism/
Fiji: an open-source platform for biological-image analysis	http://fiji.sc/	N/A
SoftMax Pro v 5.4	Molecular Devices	https://www.moleculardevices.com/products/microplate-readers/acquisition-and-analysis-software/softmax-pro-software
Leica Application Suite X software	Leica Microsystems	https://www.leica-microsystems.com/products/light-microscopes/p/leica-las-x-widefield-systems/
Flowjo (version 10)	Tree Star Inc.	https://www.flowjo.com/solutions/flowjo/downloads
Other
FLUOstar Omega microplate reader	BMG Labtech	https://www.bmglabtech.com/fluostar-omega/
Lionheart FX Automated Microscope	BioTek	https://www.biotek.com/products/imaging-microscopy-automated-cell-imagers/lionheart-fx/
Infinite M200 microplate reader	Tecan	https://lifesciences.tecan.com/plate_readers/infinite_200_pro
Zeiss LSM780, confocal laser scanning microscope	Carl Zeiss	https://www.zeiss.com/microscopy/
Zeiss Axio microscope	Carl Zeiss	https://www.zeiss.com/microscopy/
Ultra-fast switching monochromator- Polychrome V	TILL Photonics	https://www.labwrench.com/manufacturer/1363/till-photonics
ECLIPSE Ti-2 microscope	Nikon	https://www.nikon.com/about/technology/design/works/eclipse_ti2.htm
Patch-clamp amplifier	Molecular Devices	https://www.moleculardevices.com/products/axon-patch-clamp-system
Applied Biosystem StepOne System	Applied Biosystems	https://www.fishersci.ca/shop/products/stepone-real-time-pcr-system-4/4376357
Applied Biosystem Quantstudio 3 detection system	Applied Biosystems	https://www.thermofisher.com/kr/ko/home/life-science/pcr/real-time-pcr/real-time-pcr-instruments/quantstudio-3-5-real-time-pcr-system.html
Tissue Lyzer II	Qiagen	Cat#85300
Centro XS3 Luminescence Microplate Reader LB 960	EG & G Berthold	https://www.berthold.com/en/bioanalytic/products/microplate-readers/centro-lb963/
THUNDER Imager Live Cell	Leica Microsystems	https://www.leica-microsystems.com/products/thunder-imaging-systems/
NEPA21 Super Electroporator	Nepa Gene Co.	http://www.nepagene.jp/e_products_nepagene_0001.html
BD FACSCelesta™ cell Analyzer	BD Biosciences	https://www.bdbiosciences.com/ko-kr/products/instruments/flow-cytometers/research-cell-analyzers/facscelesta
Deposited data
Raw datasets and additional supplemental items	This study	https://doi.org/10.17632/8vgrh6dyfp.1