REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Anti- Gasdermin D (N-terminal), 1: 1000	ab215203;RRID: AB_2916166	Abcam
Anti- Gasdermin D (C-terminal), 1: 1000	ab210070;RRID: AB_2893325	Abcam
Anti- NLRP1 (N-terminal), 1: 1000	AF6788-SP;RRID: AB_2916167	R&D system
Anti- NLRP1 (C-terminal), 1: 1000	ab36852;RRID: AB_776633	Abcam
Anti -ACE2, 1: 1000	ab108252;RRID: AB_10864415	Abcam
Anti -TMPRSS2, 1: 1000	ab92323;RRID: AB_10585592	Abcam
Anti-actin 1: 5000	A1978;RRID: AB_476692	Sigma-Aldrich
anti-Sheep igG HRP (1/4000)	HAF016;RRID: AB_562591	R&D
Goat anti-mouse HRP (1/4000)	1034-05;RRID: AB_2794340	SouthernBiotech
Goat-anti-rabbit IgG (H+L), HRP conjugate (1/4000)	R-05072-500;RRID: AB_10719218	Advansta
Rabbit anti-Goat IgG (H+L) Secondary Antibody, HRP (1/4000)	81-1620;RRID: AB_2534006	Invitrogen
Donkey anti-Rabbit IgG (H&L) - Affinity Pure, DyLight®550 Conjugate (1/1000 IF)	DkxRb-003-D550NHSX;RRID: AB_2916168	ImmunoReagents
Anti Caspase 8 (1: 1000)	ALX-804-242-C100;RRID: AB_2050949	Enzo Life
Anti Caspase 1 (1: 1000)	AG-20B-0048-C100;RRID: AB_2916169	Adipogen
Anti Caspase 3 (1: 1000)	9662S;RRID: AB_331439	Cell Signaling
Anti gasdermin E (1: 1000)	Ab215191;RRID: AB_2737000	Abcam
Anti SARS NSP5 (1: 1000)	NBP3-07061;RRID: AB_2916170	Novusbio
Anti SARS Nucleocapsid (1: 1000)	NB100 56683;RRID: AB_838841	Novusbio
Bacterial and virus strains
BetaCoV/France/IDF0372/2020	Sylvie van der Werf and the National Reference Centre for Respiratory Viruses	Institut Pasteur (Paris, France)
hCoV-19/USA/MD-HP05647/2021 (Delta Variant)		BEI
hCoV-19/USA/OR-OHSU-PHL00037/2021 (Alpha Variant)		BEI
hCoV-19/Japan/TY7-503/2021 (Gamma Variant)		BEI
Biological samples
Plasma from Covid patients	Covid Biotoul cohort/Toulouse, France	Hospital of Toulouse
Plasma from patients with inborn mutations or autoantibodies	Institut Imagine/Covid genetic effort	Institut Imagine, Paris/France
Chemicals, peptides, and recombinant proteins
Z-VAD: 40 μM	tlrl-vad	Invivogen
Y-VAD: 40 μM	inh-yvad	Invivogen
Z-DEVD: 40 μM	S7312	Selleck Chemicals
Z-IETD: 40 μM	inh-ietd	Invivogen
MCC950: 10 μM	inh-mcc	Invivogen
VX765: 10 μM	inh-vx765i-1	Invivogen
DMF: 10 μM	S2586	Selleck Chemicals
MLN4924: 1 μM	6499	Tocris
Remdesivir: 5 μM	282T7766	Tebubio
Bortezomib: 0,1 μM	S1013	Selleck Chemicals
PF-00835231: 10 μM	S9731	Selleck Chemicals
CG-376	SE-S0475	Euromedex
Nigericin	tlrl-nig-5	Invivogen
Hoescht	62249	Invitrogen
Poly(I:C) HMW	tlrl-pic	Invivogen
Nate	lyec-nate	Invivogen
Lipofectamine 2000	11668030	Invitrogen
Lipofectamine LTX	15338030	Invitrogen
Doxycycline	S5159	Selleck chemicals
Recombinant human IL-18	(rcyec-hil18)	Invivogen
Critical commercial assays
IL-1B	88-7261-77	Fisher Scientific
IL-6	555220	BD
IL-16	DY316	R&D
Caspase 3	BMS2012INST	Invitrogen
Gasdermin E	AG-45B-0024-KI01	Adipogen
HMGB1	NBP2-62766	Novusbio
Deposited data
Original blots and microscopy images	https://doi.org/10.17632/nwhd3w9w5x.1	Mendeley dataset
Experimental models: Cell lines
THP1 KO NLRP3	Thp-konlrp3z	Invivogen
THP1	Thp-null	Invivogen
A549	A549d-nfis	Invivogen
A549-Dual™ ACE2 & TMPRSS2	a549d-cov2r	Invivogen
A549-Dual™ KO-MAVS Cells	a549d-komavs	Invivogen
A549 ACE2 & TMPRSS2 Cells	a549-hace2tpsa	Invivogen
IL-18 Reporter HEK 293 Cells	(hkb-hmil18)	Invivogen
Lonza, B-ALI kit 00193514	00193514	Lonza
Corning HTS Transwell-24 well permeable supports	CLS3379	Corning
Recombinant DNA
LentiCas9-Blast	addgen ref 52962	(Sanjana et al., 2014)
p8.91	Didier Trono lab	Didier Trono lab
pMD.2G	addgene ref 12259	Didier Trono lab
LentiGuide-Puro	addgen ref 52963	(Sanjana et al., 2014)
Vector pLVX-EF1α-IRES-Puro Containing the SARS-CoV-2, USA-WA1/2020 3C-Like Protease Gene, C145A Mutant	BEI NR-52953	BEI
pLEX307-SARS-CoV-2-3CL (NSP5)	addgene #160278	(Resnick et al., 2021)
pSC2+ NLRP1 constructs		(Robinson et al., 2020)
pLV-72-Cas9-GFP	N/A	Invivogen
pLVB-Tet ON	N/A	Invivogen
pLVB-TetR	N/A	Invivogen
pBRGEN	N/A	Invivogen
pMSCV-puro	Addgene plasmid # 68469	(Akama-Garren et al., 2016)
pMSCV-GsdmB	GeneScript	N/A
pMSCV-GsdmE	GeneScript	N/A
pMSCV-GsdmD	GeneScript	N/A
pCW57-RFP- P2A-MCS	Addgene #89182	(Barger et al., 2021)
LENTI V2 plasmid	Addgene 52961	N/A
Oligonucleotides
sgRNA targetting Gasdermin E (Exon 2)	CAGTTTTTATCCCTCACCCT	Sigma-Aldrich
sgRNA targetting Gasdermin E (Exon 2)	TAAGTTACAGCTTCTAAGTC	Sigma-Aldrich
sgRNA targetting Gasdermin E (Exon 3)	GTCGGACTTTGTGAAATACG	Sigma-Aldrich
sgRNA targetting Casp1 (Exon 2)	TTGTGAAGAAGACAGTTACC	Sigma-Aldrich
sgRNA targetting Casp1 (Exon 4)	AAGGATATGGAAACAAAAGT	Sigma-Aldrich
sgRNA targetting Gasdermin D (Exon 5)	TTAGGAAGCCCTCAAGCTCA	Sigma-Aldrich
sgRNA targetting Gasdermin D (Exon 6)	GAATGTGTACTCGCTGAGTG	Sigma-Aldrich
sgRNA targetting Gasdermin D (Exon 5)	AGGTTGACACACTTATAACG	Sigma-Aldrich
sgRNA targetting Caspase 3 (Exon 4)	CATACATGGAAGCGAATCAA	Sigma-Aldrich
sgRNA targetting Caspase 3 (Exon 5)	TGTCGATGCAGCAAACCTCA	Sigma-Aldrich
sgRNA targetting MAVS	ACCTCAGCAGATGATAGGCTCGGCC	Sigma-Aldrich
sgRNA targetting MAVS	ACCTCGCCCATCAACTCAACCCGTGC	Sigma-Aldrich
sgRNA targetting NLRP1 (Exon 2)	GCTCAGCCAGAGAAGACGAG	Sigma-Aldrich
sgRNA targetting NLRP1	GATAGCCCGAGTGACATCGG	Sigma-Aldrich
sgRNA targetting NLRP1	AGCCCGAGTGACATCGGTGG	Sigma-Aldrich
sgRNA targetting GFP	GGAGCGCACCATCTTCTTCA	Sigma-Aldrich
Fwd Q333A	GAACCTCGCATAGTCATACT GGCGGGGGCTGCTGGAATTGGGAAG	Sigma-Aldrich
Rev Q333A	CTTCCCAATTCCAGCAGCCCCCGCCA GTATGACTATGCGAGGTTC	Sigma-Aldrich
HA-GsdmD Q335A fwd2	GGCGCTGGAGgccGGCCAGAGCCTT GGGCC	Sigma-Aldrich
HA-GsdmD Q335 rev2	cgcaaccccaaccccggatccCTAGTGGGG CTCCTGGCTC	Sigma-Aldrich
HA-GsdmD Q193 fwd	cagatcgcctggagaattggctagcATGTACCCA TACGATGTTCCA	Sigma-Aldrich
HA-GsdmD Q193 rev	cgcaaccccaaccccggatcctcaCTGCAAGC ACGTGGCTC	Sigma-Aldrich
HA-GsdmD N-ter fwd	cagatcgcctggagaattggctagcATGTACCC ATACGATGTTCC	Sigma-Aldrich
HA-GsdmD N-ter rev	cgcaaccccaaccccggatcctcaATCTGTCA GGAAGTTGTGG	Sigma-Aldrich
GsdmD Q193 fwd1	aggcgccggaattagatctctcgagatggactaca aagacgatgacgacaagGGTGGAGGTGGA GGTGGA	Sigma-Aldrich
GsdmD Q193A rev1	GGCCCTCACCggcCAAGCACGTGGC TCCGG	Sigma-Aldrich
HA-GsdmD Q193A fwd2	CACGTGCTTGgccGGTGAGGGCCAG GGCCAT	Sigma-Aldrich
GsdmD Q193 rev2 pMSCV	ctcccctacccggtagaattcCTAGTGGGGC TCCTGGCTC	Sigma-Aldrich
GsdmD Q335 fwd1	aggcgccggaattagatctctcgagatggacta caaagacgatgacgacaagGGTGGAGG TGGAGGTGGAG	Sigma-Aldrich
GsdmD Q335A rev1	GGCTCTGGCCggcCTCCAGCGCC TCCTCCAA	Sigma-Aldrich
HA-GsdmD Q335A fwd2	GGCGCTGGAGgccGGCCAGAGC CTTGGGCC	Sigma-Aldrich
GsdmD Q335 rev2 pMSCV	ctcccctacccggtagaattcCTAGT GGGGCTCCTGGCTC	Sigma-Aldrich
Recombinant proteins
Recombinant SARS-COV 3CL	E-718-050	Novusbio
Recombinant SARS-CoV-2 3CL	E-720-050	Novusbio
Recombinant MERS-CoV 3CL	E-719-050	Novusbio
Recombinant human caspase-1 protein (active)	Ab39901	Abcam
Nsp3, peptidase C16 of PLpro	PX-COV-P004	proteogenix
HRV3C Protease	SAE0045	Sigma-Aldrich
Software and algorithms
Snapgene	GSL Biotech LLC, Chicago, U.S.A.	N/A
Fiji (Image J)		N/A
Benchling Software		N/A
Image Lab 6.1 (Biorad)		N/A
Biorender.com		N/A
Graphpad 8.0a		N/A
Uniprot database		N/A