REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
rabbit anti-FLAG	Merck	F7425
mouse anti-HA	BioLegend	901501
rabbit anti-actin	Sigma Aldrich	A2066
sheep anti-ORF7a	University of Dundee, MRC PPU	N/A
sheep anti-ORF3a	University of Dundee, MRC PPU	N/A
donkey anti-mouse IgG	LI-COR	926-68072
goat anti-mouse IgG	LI-COR	926-32210
donkey anti-rabbit IgG	LI-COR	926-68073
goat anti-mouse IgG	LI-COR	926-32211
donkey anti-goat IgG	LI-COR	926-68074
anti-HA	Abcam	ab20084
anti-alpha-tubulin	Abcam	ab15568
anti-VDAC1	Abcam	ab14734
anti-lamin A/C	Abcam	ab133256
mouse anti-Tom20	Abcam	ab283317
rabbit anti-Tom70	ProteinTech	14528-1-AP
rabbit anti-Calnexin	Cell Signalling Technology	D2B6N
rabbit anti-Syntaxin 6	Cell Signalling Technology	C34B2
mouse anti-alpha-tubulin	ProteinTech	66031-1
mouse anti-EEA1	BD Biosciences	14/EEA1
mouse anti-CD63	BioLegend	H5C6
mouse anti-LAMP1	BioLegend	H4A3
rabbit anti-TGN46	Abcam	ab50595
rabbit anti-HA	Cell Signalling Technology	C29F4
rat anti-HA	Roche	3F10
mouse anti-OPG2	McKenna et al., 2016	N/A
mouse anti-Strep	IBA lifesciences	2-1507-001
mouse anti-Spike	GeneTex	1A9
rabbit anti-MAVS	Cell Signalling Technology	3993
rabbit anti-FLAG	Sigma Aldrich	F2555
Alexa Fluor 488 goat anti-rat IgG	Invitrogen	A-11006
Alexa Fluor 488 goat anti-mouse IgG	Invitrogen	A-11001
Alexa Fluor 488 donkey anti-sheep IgG	Invitrogen	A-11015
Alexa Fluor Plus 555 goat anti-rabbit IgG	Invitrogen	A32732
rabbit anti-TIM22	Proteintech	14927-1-AP
rabbit anti-ERLIN2	Proteintech	14781-1-AP
Rabbit polyclonal anti-COX4-I	This paper	N/A
Bacterial and virus strains
E. coli DH5a	Thermofisher Scientific	18258012
SARS-CoV-2 (B lineage)	UK Health Security Agency	BetaCoV/Australia/VIC01/2020
SARS-CoV-2 (B.1.1.7)	UK Health Security Agency	BetaCoV/England/ MIG457/2020
SARS-CoV-2 (B.1.617.2-POR1)	UK Health Security Agency	ASL516
SARS-CoV-2 (B.1.617.2-POR2)	UK Health Security Agency	ASL517
SARS-CoV-2 (B.1.617.2)	Imperial College London	GISAID Accession EPI_ISL_1731019
SARS-CoV-2 (Wuhan)	University of Bristol	Genbank Accession MW041156.1
Sendai Virus	University of London	Cantell strain
Chemicals, peptides, and recombinant proteins
Dulbecco’s Modified Eagle’s Medium (DMEM)	Invitrogen	11965092
Fetal Bovine Serum (FBS)	Gibco	10500-064
L-glutamine	Gibco	25030081
Penicillin/Streptomycin	Gibco	15070063
Trypsin-EDTA	Gibco	R001100
Phosphate-buffered saline (PBS)	Thermoscientific	10010023
Lipofectamine 2000	Invitrogen	11668019
4% paraformaldehyde	Thermofisher Scientific	15670799
Saponin	Thermoscientific Chemicals	A18820.14
Triton X-100	Thermoscientific Chemicals	A16046.AE
Bovine serum albumin	Sigma Aldrich	A9418
ProLong Gold Antifade + DAPI	Invitrogen	P36931
NP40	Thermoscientific	85124
Halt Protease and Phosphatase Inhibitor Cocktail	Thermofisher Scientific	78440
SuperScript III	Invitrogen	18080093
SYBR Green Master Mix	Thermofisher Scientific	4309155
TNF-α	Peprotech	300-01A
Doxycycline	Sigma Aldrich	D3072
Precast Novex 10–20% tricine protein gels	Thermofisher Scientific	EC66252BOX
RIPA buffer	Thermofisher Scientific	89900
Staurosporine	Abcam	ab120056
Incucyte caspase 3/7 green dye	Sartorius	4440
ABT-737	Merck	197333-10MG
Z-VAD	Sigma Aldrich	V116
Z-VEID-FMK	Sigma Aldrich	218757-250ug
Caspase-3/7 Inhibitor I	Merck	218826-1MG
Ac-FLTD-CMK	MedChem Express	HY-111675
Z-LEHD-FMK	Sigma Aldrich	218728-1MG
Z-DEVD-FMK	Santa Cruz	sc-311558
DMSO	Invitrogen	D12345
HEPES	Merck	H0887-100ML
nonessential amino acids	Gibco	11140050
G418	Gibco	11811031
Hygromycin B	Roche	10843555001
OptiMem	Gibco	31985070
T7 polymerase	Promega	P2075
Puromycin	Gibco	A1113803
IFN-ɑ	Peprotech	300-02AA
PMA	Sigma Aldrich	P8139
cOmplete Mini EDTA-free protease inhibitor	Roche	11836170001
anti-FLAG agarose	Merck	A2220
MitoTracker Red CM-H2XRos	Invitrogen	M7513
Glycine	Invitrogen	15527013
glutaraldehyde	Sigma Aldrich	G5882
UA-Zero EM Stain	Agar Scientific	AGR1000
digitonin	Merck Millipore	300410
Nuclease S7 Micrococcal nuclease	Sigma Aldrich	10107921001
Trypan blue	Sigma Aldrich	T8154
Flexi rabbit reticulocyte lysate	Promega	L4540
EasyTag EXPRESS 35S Protein Labelling Mix	Perkin Elmer	NEG772002MC
endoglycosidase Hf	New England Biolabs	P0703S
proteinase K	Carl Roth	7528.2
PMSF	Carl Roth	6367.2
[35S] methionine	Hartmann Analytic	SCM-01
Sodium carbonate	Merck	6398.1
Critical commercial assays
RNeasy Mini Kit	Qiagen	74106
HA Tag Magnetic IP/Co-IP kit	Pierce	88838
Q5 site directed mutagenesis kit	New England Biolabs	E0554S
Human IFN-β Quantikine ELISA	Bio-Techne	DIFNB0
Cytochrome c Release Assay	Abcam	ab65311
T7 mMessage kit	Invitrogen	K0441
RNA Clean and Concentrator	Zymo Research	R1014
Dual luciferase kit	Promega	E1910
Miniprep kit	Qiagen	27104
MycoAlert PLUS Assay	Lonza	LT07-710
Stratagene QuikChange	Agilent Technologies	200519
Subcellular fractionation	Thermofisher Scientific	78840
Epoxy Resin (Araldite CY212) Kit	Agar Scientific	AGR1030
SP6 mMESSAGE mMACHINE kit	Invitrogen	AM1340
Mitochondria Isolation Kit, human	Miltenyi Biotec	130-094-532
DMEM w/High Glucose and w/o Glutamine, Lysine and Arginine	Gibco	A1443101
Deposited data
Proteomics data	PRIDE	PXD037765
epicov.org	GISAID; Elbe et al., 201780	http://gisaid.org/EPI_SET_221101zc
Experimental models: Cell lines
HeLA	ATCC	CCL-2
HEK293T	ATCC	CRL-3216
A549	ATCC	CCL-185
Vero	ATCC	CRL-1586
A549+ACE2+TMPRSS2	Rihn et al., 2021129	N/A
HEK293T-Flp-In™ T-Rex™	Thermofisher Scientific	R78007 RRID: CVCL_U421
Vero+ACE2+TMPRSS2	Rihn et al., 2021129	N/A
ORF3c-FLAG inducible A549	This paper	N/A
Oligonucleotides
ISG54_FWD ATGAAGACGGTGCTGAATACTAGTGA	This paper	N/A
ISG54_REV TGGTGAGGGCTTTCTTTTTCC	This paper	N/A
ISG56_FWD ACCATGGGAGAGAATGCTGAT	This paper	N/A
ISG56_REV GCCAGGAGGTTGTGC	This paper	N/A
IFN-β_FWD CATCAACTATAAGCAGCTCCA	This paper	N/A
IFN-β_REV TTCAAGTGGAGAGCAGTTGAG	This paper	N/A
ORF3cFLAG_FWD CCGCTCGAGGCCACC ATGCTACTCC	This paper	N/A
ORF3cFLAG_REV TTTGTTCGAACCGCGGTTACTTA TCGTCGTCATCCTTGTAATCGGAGCCTCCAGAGC CTCCTGATTTT	This paper	N/A
GAPDH_FWD ATCAACGACCCCTTCATTGACC	Lu et al., 202220	N/A
GAPDH_REV CCAGTAGACTCCACGACATACTCAGC	Lu et al., 202220	N/A
NFKBIA_FWD CTGCAGGCCACCAACTACAA	Lu et al., 202220	N/A
NFKBIA_REV CAGCACCCAAAGTCACCAAGT	Lu et al., 202220	N/A
CCL2_FWD CTTCTGGGCCTGCTGTTCA	Lu et al., 202220	N/A
CCL2_REV CCAGCCTACTCATTGGGATCA	Lu et al., 202220	N/A
CXCL8_FWD AGAAACCACCGGAAGGAACCATCT	This paper	N/A
CXCL8_REV AGAGCTGCAGAAATCAGGAAGGCT	This paper	N/A
Recombinant DNA
pCAG-ORF3cHA	This paper	Addgene ID: 208653
pCAG-ORF3cStrep	This paper	Addgene ID: 208728
pL3cSGRLuc	This paper	Addgene ID: 208729
pcDNA3.1-PGAM5-FLAG	GenScript	CloneID OHu01661D
pcDNA3.1-HA-MAVS	Unterholzner et al., 2011130	N/A
pcDNA3.1-FLAG-MAVS	Unterholzner et al., 2011130	N/A
pCAG-ORF3c-FLAG	This paper	N/A
pCAG-ORF3c-FLAG-Q5Y	This paper	N/A
pISG56.1-luc	Cleveland Clinic, Lerner Research Institute	N/A
TBK1	Unterholzner et al., 2011130	N/A
TRIFΔRIP	Unterholzner et al., 2011130	N/A
IRF3-5D	Unterholzner et al., 2011130	N/A
RIG-I-CARD	University of Surrey	N/A
MDA5	University of St Andrews	N/A
pCAG-ORF3a-FLAG	Shandong University	N/A
pCAG-NSP6-FLAG	Shandong University	N/A
pCAG-NSP9-FLAG	Shandong University	N/A
pCAG-NSP12-FLAG	Shandong University	N/A
pcDNA3.1-TOMM70A-FLAG	GenScript	Clone ID OHu01661D
pLKO.neo.EGFPnls-TetR	MRC University of Glasgow Centre for Virus Research	N/A
pLKO.DCMV-TetO.mcs	MRC University of Glasgow Centre for Virus Research	N/A
pLKO.DCMV.TetO.ORF3c	This paper	N/A
pISRE-luc	Unterholzner et al., 2011130	N/A
pNF-κB-luc	Unterholzner et al., 2011130	N/A
pAP-1-luc	Unterholzner et al., 2011130	N/A
pIFN-β-luc	Unterholzner et al., 2011130	N/A
pcDNA3.1-GFP-FLAG	This paper	N/A
pcDNA3.1-TOMM20-FLAG	This paper	N/A
Software and algorithms
Prism version 7.0c for Mac OS X	GraphPad software	N/A
MATLAB software	MathWorks	N/A
SnapGene	GSL Biotech LLC	N/A
Image Studio	LI-COR	N/A