REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Anti-NSP1 sheep polyclonal antibody	MRC-University of Glasgow Centre for Virus Research (CVR)	N/A
Anti-NSP8 sheep polyclonal antibody	MRC CVR	N/A
Anti-NSP9 sheep polyclonal antibody	MRC CVR	N/A
Anti-NSP16 sheep polyclonal antibody	MRC CVR	N/A
Anti-Actin antibody	Developmental Studies Hybridoma Bank JLA20	Cat. # 528068
PE-labeled anti-NGFR antibody	Biolegend	Cat. # 345105
Rabbit anti-SARS-Cov-2 Spike Antibody	Sino	Cat. # 40591-T62-100
PacBlue-labeled streptavidin	Thermo	Cat. # S1222
PE-labeled anti-Rabbit	Thermo	Cat. # P-2771MP
anti-puromycin antibody	EMD Millipore	Cat. # MABE343 Clone 12D10
Bacterial and Virus Strains
2019-nCoV/USA_USA WA1/2020 (WA1)	WRCEVA	N/A
Chemicals, Peptides, and Recombinant Proteins
HMW poly(I:C)	Invivogen	Cat. # tlrl-pic
IFN-beta	R&D Systems	Cat. # 8499-IF-010/CF
HaloTag® Alexa Fluor® 660 Ligand	Promega	Cat. # G8471
Halolink Resin	Promega	Cat. # G1915
Biotin Picolyl Azide	Click Chemistry Tools	Cat. # 1167-25
5 ethyl uridine	Jena Bioscience	Cat. # CLK-N002-CSTM
Critical Commercial Assays
QUANTI-Blue	Invivogen	Cat. # rep-qbs
1-Step Human Coupled IVT-DNA	Thermo	Cat. # 88882
Rabbit Reticulocyte Lysate System	Promega	Cat. # L4960
TransIT-mRNA Transfection Kit	Mirus	Cat. # MIR2225
HiScribe T7 ARCA mRNA Kit	NEB	Cat. # E2060S
Deposited Data
SARS-CoV-2 Protein Capture and RNA Sequencing	NCBI Short Read Archive (SRA)	Accession # PRJNA665692
Nascent and total RNA-Seq data	NCBI Short Read Archive (SRA)	Accession # PRJNA665581
Pre-catalytic human spliceosome structure	Charenton et al., 2019	PDB: 6QX9
Structure of S domain of 7SL	Kuglstatter et al., 2002	PDB: 1MFQ
Structure of SRP-Ribosome Complex	Voorhees and Hegde, 2015	PDB: 3JAJ
Structure of Ebp1-ribosome complex	Wild et al., 2020	PDB: 6SXO
Structure of the human 40S ribosome	Ameismeier et al., 2018	PDB: 6G5H
Structure of mRNA path through ribosome	Simonetti et al., 2020	PDB: 6YAL
Structure of SERBP1	Brown et al., 2018	PDB: 6MTE
Structure of Stm1	Ben-Shem et al., 2011	PDB: 4V88
APPRIS database	Rodriguez et al., 2013	N/A
Experimental Models: Cell Lines
HEK293T	ATCC	Cat. # CRL-3216
Vero E6	J.L. Whitton and Michele Bouloy	N/A
HEK-Blue-ISG	Invivogen	Cat. # hkb-igs-1
A549	ATCC	Cat. # CCL-185
Calu3	ATCC	Cat. # HTB-55
Oligonucleotides
Primers for In-vitro transcription	See Table S4	N/A
Primers used for qPCR	See Table S2	N/A
siRNA targeting SRP19	Dharmacon	L-019729-01-0005
siRNA targeting SRP54	Dharmacon	L-005122-01-0005
Recombinant DNA
Template used in mRNA generation	See Table S5	N/A
NSP1	Kim et al., 2020a	RRID: Addgene_141255
NSP2	Kim et al., 2020a	RRID: Addgene_141256
PLPRO (NSP3)	Kim et al., 2020a	RRID: Addgene_141257
NSP4	Kim et al., 2020a	RRID: Addgene_141258
NSP5	Kim et al., 2020a	RRID: Addgene_141259
NSP6	Kim et al., 2020a	RRID: Addgene_141260
NSP7	Kim et al., 2020a	RRID: Addgene_141261
NSP8	Kim et al., 2020a	RRID: Addgene_141262
NSP9	Kim et al., 2020a	RRID: Addgene_141263
NSP10	Kim et al., 2020a	RRID: Addgene_141264
NSP11	Kim et al., 2020a	RRID: Addgene_151991
RNA-pol (NSP12)	Kim et al., 2020a	RRID: Addgene_141265
Heli (NSP13)	Kim et al., 2020a	RRID: Addgene_141266
NSP14	Kim et al., 2020a	RRID: Addgene_141267
NSP15	Kim et al., 2020a	RRID: Addgene_141268
NSP16	Kim et al., 2020a	RRID: Addgene_141269
ORF3A	Kim et al., 2020a	RRID: Addgene_141271
ORF3B	Kim et al., 2020a	RRID: Addgene_141272
E	Kim et al., 2020a	RRID: Addgene_141273
M	Kim et al., 2020a	RRID: Addgene_141274
ORF6	Kim et al., 2020a	RRID: Addgene_141275
ORF7A	Kim et al., 2020a	RRID: Addgene_141276
ORF7B	Kim et al., 2020a	RRID: Addgene_141277
ORF8	Kim et al., 2020a	RRID: Addgene_141278
ORF9B	Kim et al., 2020a	RRID: Addgene_141280
N	Kim et al., 2020a	RRID: Addgene_149330
NSP11 (pGBW-m4133457)	Ginko Bioworks	RRID: Addgene_151991
pB-TAG-ERN	Kim et al., 2016	RRID: Addgene_80476
NGFR	Izon et al., 2001	RRID: Addgene_27489
Software and Algorithms
Imaris	Oxford Instruments, Imaris	https://imaris.oxinst.com
Transform-restrained Rosetta Algorithm	Yang et al., 2020	https://yanglab.nankai.edu.cn/trRosetta/
Pymol	Schrodinger	https://pymol.org/2/
Modeler version 9.24	Webb and Sali, 2016	https://salilab.org/modeller/manual/
FloJo analysis software	FlowJo, LLC.	https://www.flowjo.com/solutions/flowjo
MAFFTT (v7.407)	Rozewicki et al., 2019	https://mafft.cbrc.jp/alignment/server/
Geneious	Geneious	https://www.geneious.com
Integrative Genomics Viewer	Robinson et al., 2011	http://software.broadinstitute.org/software/igv/
Morpheus	Broad Institute	https://software.broadinstitute.org/morpheus/
Molecular Signatures Database Gene Ontology Biological Processes and Reactome	Liberzon et al., 2015	https://www.gsea-msigdb.org/gsea/msigdb
Trimmomatic	Bolger et al., 2014	https://github.com/timflutre/trimmomatic
STAR Aligner	Dobin et al., 2013	https://github.com/alexdobin/STAR
PICARD	“Picard Toolkit.” 2019. Broad Institute, GitHub Repository.	https://broadinstitute.github.io/picard/
Bowtie2	Langmead and Salzberg, 2012	http://bowtie-bio.sourceforge.net/bowtie2/index.shtml