TABLE 2.
Overview of genome-wide CRISPR screens for coronavirus host factorsc
| Group (referencea) | Cell line(s) | Library (reference) | Virus strain(s) | Validated gene(s)b | Pathway(s) | Inhibitor(s) tested |
|---|---|---|---|---|---|---|
| Daniloski et al. (157) | A549-ACE2 | GeCKOv2 library (171) | SARS-CoV-2 (USA/WA-1 isolate) | ACE2 | Viral receptor | Cathepsin L inhibitors (Odanacatib, SID26681509, ALLN), PIK3C3 inhibitors (Serabelisib, Idelalisib, Buparlisib, PIK-III, Compound 19, SAR405, Autophinib), PRKCA inhibitors (Sotrastaurin, Enzastaurin, Tamoxifen), MMP12 inhibitors (Doxycycline, Ilomastat), BRPF1 inhibitor (GSK6853), DRD2 inhibitor (Olanzapine), MAPK3 inhibitors (Binimetinib, Mirdametinib), CALR inhibitor (Gentamicin), HDAC9 inhibitors (BRD4354, TMP195, Vorinostat, Belinostat, Panobinostat, Pracinostat), calcium channel antagonist (Amlodipine) |
| CCDC22, NPC1, RAB7A | Endosomal entry | |||||
| ATP6AP1, ATP6V1A, CTSL, TMPRSS2 | Spike cleavage and membrane fusion | |||||
| COMMD3, PIK3C3, SNX27, VPS35 | Endosome recycling | |||||
| SPEN | Transcription | |||||
| BAX, CNOT4, CXCL5, FBXO27, FBXO33, HDAC9, HNRNPC, INO80E, PCID2, PRKCA, PSMB5, SIGMAR1, TMEM165, TMPRSS13, TOR1AIP1, TRIM4, ZC3H18 | Other functions | |||||
| Wang et al. (158) | Huh7.5.1, Huh7.5.1-ACE2-IRES-TMPRSS2 | GeCKOv2 library (171) | SARS-CoV-2 (USA/WA-1 isolate), HCoV-OC43, HCoV-229E | ACE2 | Viral receptor | PI3K inhibitor (SAR405), PIKfyve inhibitor (YM201636), SREBP activation inhibitor (Fatostatin), MBTPS1 inhibitor (PF-429242), 25-hydroxycholesterol (25-HC), KEAP1-NRF2 activator (Bardoxolone) |
| CCZ1B, RAB7A, VPS16 | Endosome maturation | |||||
| MBTPS1, MBTPS2, PIKFYVE, SCAP | Cholesterol homeostasis | |||||
| BECN1, PIK3R4, UVRAG, VAC14 | Phosphatidylinositol kinase complexes | |||||
| EXOC2, EXOC6, EXOC8 | Exocyst complex | |||||
| TMEM106B | Lysosome/autophagosome-related function | |||||
| ARF5 | Other functions | |||||
| Hoffmann et al. (159) | Huh7.5 | 332 human genes that were previously identified in SARS-CoV-2 protein interactome (142) | SARS-CoV-2 (USA/WA-1 isolate), HCoV-OC43, HCoV-229E, HCoV-NL63 |
ACE2 RAB2A, RAB7A, VPS11, VPS39 |
Viral receptor Common Rabs and HOPS |
NA |
| EMC1, SCAP, NPC2, SREBF1, SREBF2 | Cholesterol homeostasis | |||||
| RAB10, RAB14 | SARS-CoV-2 Rabs | |||||
| GPAA1, PIGO, PIGS | GPI biosynthesis | |||||
| HS2ST1, INSIG1, MIB1, RAB18, RAB1A, RAB8A, RAB5C | Other functions | |||||
| Schneider et al. (160) | Huh7.5 | Brunello genome-wide CRISPR library (172) | SARS-CoV-2(USA/WA-1 isolate), HCoV-OC43, HCoV-NL63, HCoV-229E | ACE2, ANPEP | Viral receptor | NA |
| MBTPS1, MBTPS2, SREBF2 | SREBP control of lipid biosynthesis | |||||
| EXT2 | Glycosaminoglycan biosynthesis: heparin sulfate | |||||
| PIK3C3, VAC14 | PIP biosynthesis at late endosome | |||||
| COG3 | COG and exocyst complex | |||||
| BMPR1A, CDX2, DDX1, DHX36, EGLN1, EP300, NRIP1, OR1A1, RAB7A , RIC1, RTCB, SLC30A1, SLC39A9, TM9SF3, TMEM106B, TMEM41B, VMP1, VRK1 | Other functions | |||||
| Wei et al. (161) | Vero E6 | African green monkey genome-wide CRISPR knockout library (CP0070) designed according to the Brunello human genome-wide library (173) | SARS-CoV-2 (USA/WA-1 isolate), rcVSV-SARS-CoV-2-S, HKU5-SARS-CoV-1-S, MERS-CoV (WT and T1015N) | ACE2 | Viral receptor | Cathepsin L inhibitor (Calpain inhibitor III), SMARCA4 and SMARCA2 inhibitor (PFI-3), SMAD3 inhibitor (SIS3) |
| ARID1A, SMARCA4, SMARCE1 | SWI/SNF complex | |||||
| SMAD3, SMAD4 | RUNX3 regulates CDKN1A transcription | |||||
| CTSL | Cystatin and endolysosome lumen | |||||
| CABIN1, HIRA | Regulator of histone variant H3.3 | |||||
| SMARCA5 | NURF complex | |||||
| ACVR1B, ATRX, DOLK, DPF2, DYRK1A, HMGB1, JMJD6, KDM6A, PCBD1, PHF6, PHIP, PIAS1, PIAS2, RAD54L2, SIAH1, UBXN7 | Other functions | |||||
| Zhu et al. (162) | A549-ACE2 | Brunello genome-wide CRISPR library (Addgene no. 73178) (172) | Patient-isolated SARS-CoV-2 SH01 strain | ACE2 | Viral receptor | TMPRSS2 inhibitor (Camostat mesilate), Cathepsin B and L inhibitor (aloxistatin), NPC1 inhibitor (U18666A) |
| CTSL | Membrane fusion | |||||
| C18orf8, CCZ1, CCZ1B, RAB7A, VSP29, VSP35 | Retromer-associated genes | |||||
| C16orf62, CCDC22, CCDC93, COMMD10, COMMD2, COMMD3-BMI1, COMMD3, COMMD4, COMMD5, COMMD7, COMMD8 | CCC complex | |||||
|
CCDC53, KIAA0196, KIAA1033, ACTR2, ACTR3, ARPC3, ARPC4 NPC1, NPC2 ASCC3, TFE3, WDR81, WDR91 |
WASH complex Arp2/3 complex Cholesterol trafficking Other functions |
|||||
| Baggen et al. (163) | Huh7 | Brunello genome-wide CRISPR library (Addgene no. 73179) (172) | SARS-CoV-2 (SARS-CoV-2/Belgium/GHB-03021/2020), HCoV-229E | ACE2, ANPEP, EXT1, ITGB6 | Viral receptor/heparan sulfate synthesis | PI3K type 3 inhibitors (VPS34-IN1, VPS34-IN2, SAR405, autophinib) |
| CCZ1B, PTPN23, RSG1 | Membrane/vesicle trafficking | |||||
| PIK3C3, TMEM41B | Endocytic trafficking and autophagy | |||||
| OSBPL9, PTDSS1, TMEM30A | Lipid homeostasis | |||||
| TMEM106B | Lysosome/autophagosome-related function |
a
Peer-reviewed references.
b
Candidate genes validated by SARS-CoV-2 infection. The genes that could not significantly reduce SARS-CoV-2 infection are marked with underline.
c
WT, wild type; MMP12, Matrix metalloproteinase 12; BRPF1, bromodomain and PHD finger containing 1; DRD2, dopamine receptor D2; MAPK3, mitogen-activated protein kinase 3; HDAC9, histone deacetylase 9; 25-HC, 25-hydroxycholesterol; HOPS, homotypic fusion and vacuole protein sorting; GPI, glycosylphosphatidylinositol; NA, not applicable; SREBP, sterol regulatory element-binding protein; PIP, phosphatidylinositol; COG, cis-oligomeric Golgi; rcVSV, replication-competent vesicular stomatitis virus; NURF, Nucleosome Remodeling Factor; CCC, COMMD/CCDC22/CCDC93; WASH, Wiskott–Aldrich syndrome protein and SCAR homologue; Arp2/3, actin-related protein 2/3.