Mapping the SARS-CoV-2–Host Protein–Protein Interactome by Affinity Purification Mass Spectrometry and Proximity-Dependent Biotin Labeling: A Rational and Straightforward Route to Discover Host-Directed Anti-SARS-CoV-2 Therapeutics
Abstract
:1. Introduction
1.1. Structural Features of SARS-CoV-2
1.2. AP-MS and BioID
1.3. Data Filtering and Graphical Network Representation
1.4. Validation Experiments
1.5. Mapping PTMs Profiles
2. Mapping the SARS-CoV-2 Interactome
2.1. Mapping the SARS-CoV-2 Interactome Generated in HEK-293 Cells by AP-MS
References | Bait | Prey (Gene Name) or Process | Compound | In Vitro Evidence (1) | Compound Approval Status |
---|---|---|---|---|---|
Gordon et al. [17] | (2) | mRNA translation | PS3061 | IC50 = 20–500 nM | Preclinical compound |
Ternatin-4 | IC50 = 71 nM | Preclinical compound | |||
Zotatifin | IC50 = 1.5 nM | Drug in clinical trial | |||
E | BRD2/4 | dBET6 | IC50 = 14 nM | Preclinical compound | |
MZ1 | Kd = 120–228 nM | Preclinical compound | |||
M | ATP6AP1/ATP6V1A | Bafilomycin A1 | IC50 = 100 nM | Preclinical compound | |
N | CSNK2A2 | Silmitasertib | IC50 = 1 nM | Drug in clinical trial | |
Nsp6 | SIGMAR1 | Clemastine | Ki = 67 nM | FDA-approved | |
Haloperidol | Ki = 2.91 nM | FDA-approved | |||
Hydroxychloroquine | Ki = 85 nM | FDA-approved | |||
PB28 | Ki = 13 nM | Preclinical compound | |||
Siramesine | Ki = 17 nM | Drug in clinical trial | |||
Cloperastine | Ki = 20 nM | FDA-approved | |||
ATP6AP1/ATP6V1A | Bafilomycin A1 | IC50 = 100 nM | Preclinical compound | ||
Nsp12 | RIPK1 | Ponatinib | IC50 = 12 nM | FDA-approved | |
Nsp14 | IMPDH2 | Mycophenolic acid | IC50 = 20 nM | FDA-approved | |
ORF9c | SIGMAR2 | Clemastine | Ki = 15 nM | FDA-approved | |
Haloperidol | Ki = 54.1 nM | FDA-approved | |||
Hydroxychloroquine | Ki = 772 nM | FDA-approved | |||
PB28 | Ki = 13 nM | Preclinical compound | |||
Siramesine | Ki = 0.12 nM | Drug in clinical trial | |||
Cloperastine | Ki = 900 nM | FDA-approved | |||
F2RL1 | AZ3451 (PAR2 negative allosteric modulator) | pKd = 15 | Preclinical compound | ||
ORF10 | VCP | ML240 | IC50 = 100 nM | Preclinical compound | |
Bouhaddou et al. [63] | (3) | AXL | Gilteritinib | IC50 = 0.807 μM | FDA-approved |
N/A | MAPK11, MAPK14 | Ralimetinib | IC50 = 0.873 μM | Drug in clinical trial | |
(4) | MAPK13 | MAPK13-IN-1 | IC50 = 4.63 μM | Preclinical compound | |
N/A | MAPK14 | ARRY-797 | IC50= 0.913μM | Drug in clinical trial | |
(4) | MAPK14, MAPK11, MAPK12, MAPK13 | SB203580 | IC50 = 4.76μM | Preclinical compound | |
N | CSNK2A1, CSNK2A2 | Silmitasertib | IC50 = 2.34 μM | Drug in clinical trial | |
(5) | PIKFYVE | Apilimod | IC50 = 0.08 μM IC50 = 0.007 μM | Drug in clinical trial | |
(6) | CDK | Dinaciclib | IC50 = 0.127 μM IC50 = 0.032 μM | Drug in clinical trial | |
Gordon et al. [18] | Nsp6 | SIGMAR1 | Fluphenazine | pIC50 = 6.46 | FDA approved |
Chlorpromazine | pIC50 = 6.05 | FDA approved | |||
Haloperidol | pIC50 = 5.684 | FDA approved | |||
Clemastine | pIC50 = 6.264 | FDA approved | |||
Meclizine | pIC50 = 5177 | FDA approved | |||
Amodiaquine | pIC50 = 6.428 | FDA approved | |||
Hydroxychloroquine | pIC50 = 6.062 | FDA approved | |||
Chloroquine | pIC50 = 6.036 | FDA approved | |||
Amiodarone | pIC50 = 6.779 | FDA approved | |||
Tamoxifen | pIC50 = 6.563 | FDA approved | |||
Triparanol | pIC50 = 6.439 | FDA approved | |||
Clomiphene | pIC50 = 6.257 | FDA approved | |||
Propranolol | pIC50 = 5.435 | FDA approved | |||
Nsp7 | PTGES2 | Indomethacin | pIC50 = 4.258 | FDA approved | |
ORF9c | SIGMAR2 | Fluphenazine | pIC50 = 6.46 | FDA approved | |
Chlorpromazine | pIC50 = 6.05 | FDA approved | |||
Haloperidol | pIC50 = 5.684 | FDA approved | |||
Clemastine | pIC50 = 6.264 | FDA approved | |||
Meclizine | pIC50 = 5177 | FDA approved | |||
Amodiaquine | pIC50 = 6.428 | FDA approved | |||
Hydroxychloroquine | pIC50 = 6.062 | FDA approved | |||
Chloroquine | pIC50 = 6.036 | FDA approved | |||
Amiodarone | pIC50 = 6.779 | FDA approved | |||
Tamoxifen | pIC50 = 6.563 | FDA approved | |||
Triparanol | pIC50 = 6.439 | FDA approved | |||
Clomiphene | pIC50 = 6.257 | FDA approved | |||
Propranolol | pIC50 = 5.435 | FDA approved | |||
Stukalov et al. [21] | N/A | Inducers of DNA damage | Tirapazamine | 2 µM (7) | Drug in clinical trial |
Rabusertib | 1 µM (7) | Drug in clinical trial | |||
N/A | mTOR inhibitor | Rapamycin | 1 µM (7) | FDA-approved | |
ORF3 | FLT3/AXL | Gilteritinib | 0.5 µM (7) | FDA-approved | |
(8) | AKT | Ipatasertib | 5 µM (7) | Drug in clinical trial | |
N/A | Matrix metalloproteinase inhibitors | Prinomastat | 2 µM (7) | Drug in clinical trial | |
Marimastat | 2 µM (7) | Drug in clinical trial |
2.2. Mapping the SARS-CoV-2 Interactome Generated in A549 Lung Carcinoma Cells by AP-MS
2.3. Mapping the SARS-CoV-2 Interactome Generated in HEK293 Cells by BioID
2.4. Mapping the SARS-CoV-2 Interactome Generated in A549 Cells by BioID
3. Discussion
3.1. Common Host Interactors Across Core PPI Datasets
3.2. Challenges and Limitations of These Approaches
4. Conclusions
5. Perspectives
Author Contributions
Funding
Conflicts of Interest
References
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References | Biological Systems | Interactors Identification Methods | PPI Analysis | SARS-CoV-2-Human Interaction Network and Enrichment Analysis (Main Pathways) | Data Availability and Web Resources |
---|---|---|---|---|---|
Gordon et al. [17] | Transient transfection in HEK-293 cells for PPI studies; Vero E6 cells for drug repurposing. | AP-MS: either N- or C- terminus 2xStrep tagging followed by AP-MS. | SAINTexpress (1); MiST (2); Cytoscape; GO (3) enrichment analysis. | DNA replication, epigenetic and gene-expression regulators, vesicle trafficking, lipid modification, RNA processing and regulation, ubiquitin ligases, signaling, nuclear transport machinery, cytoskeleton, mitochondria and the extracellular matrix. | MS raw data deposited to the PX (4) Consortium (www.ebi.ac.uk/pride/archive/projects/PXD018117). PPI networks uploaded to NDEx (5) (https://public.ndexbio.org/#/network/43803262-6d69-11ea-bfdc-0ac135e8bacf). |
Gordon et al. [18] | Transient transfection in HEK-293 cells for PPI studies; HeLa cells for IF5 experiments; A549-ACE2 and Caco2 cells for validation on viral life cycle; Vero E6 and A549-ACE2 cells for drug repurposing. | AP-MS: either N- or C- terminus 2xStrep tagging followed by AP-MS. | SAINTexpress; MiST; Cytoscape; GO (3) enrichment analysis. | Regulation of RNA metabolism and ribosome biogenesis, endosomal and Golgi vesicle transport, proteasomal catabolism, cellular response to heat and regulation of intracellular protein transport. | MS-proteomics data deposited to the PX (6) Consortium (https://www.ebi.ac.uk/pride/archive/projects/PXD021588). PPI networks can be found either in NDEx (5) and at https://kroganlab.ucsf.edu/network-maps. |
Davies et al. [19] | Transient transfection in HEK-293 cells. | AP-MS: either N- (nsp2) or C- (nsp4) terminus FLAG tagging followed by AP-MS. | R statistics software. Cytoscape; GO (3) enrichment analysis. | Nsp2 interactors are involved in a number of host cell processes, including metabolic processing and transport. Nsp4 interactors showed multiple enriched biological processes, such as cell organization and biogenesis, transport, and metabolic processes. | N/A |
Li et al. [20] | Transient transfection in HEK-293 cells. PBMC for proteomic perturbation in COVID-19 patients primary cells. | AP-MS: N- terminus 3xFlag-tagging followed by AP-MS. | MiST; Cytoscape; GO (3) enrichment analysis. | Inflammation and immune responses, ATP biosynthesis and metabolic processes, nucleotide-excision repair, protein methylation and alkylation, translation initiation, reactive oxygen species metabolic process, ER stress, and mRNA transport. | Datasets deposited to the PX (4) Consortium (http://proteomecentral.proteomexchange.org) via the iProX partner repository (dataset identifier IPX0002285000). |
Stukalov et al. [21] | Lentiviral mediated transduction of A549 cells for PPI identification. A549-ACE2 for both OMICS perturbation and drug repurposing. | AP-MS: C- terminus HA tagging followed by AP-MS. | R statistics software; GO (3) enrichment analysis. | Stress and DNA damage response, regulation of transcription, cell junction organization, cell survival, motility and innate immune responses. | N/A |
Samavarchi-Tehrani et al. [22] | A549 cells transduced by lentiviral constructs (except for nsp1 and nsp3, whose constructs where transfected). | BioID: miniTurbo enzyme fused separately at both N- and C- terminus of each bait, modified proteins purification followed by MS. | SAINTexpress; Cytoscape; GO (3) enrichment analysis; Humancellmap.org. | Regulation of cell cycle processes, antigen processing, viral genome replication, transcription, regulation of innate immunity, DNA damage checkpoint, histone binding, proteasomal degradation. | Virus–host proximity interactome dataset is available at https://covid19interactome.org/ |
St-Germain et al. [23] | Stably transfected HEK-293 cells | BioID: BirA* enzyme fused at the N- terminus of 14 viral baits, modified proteins purification followed by MS. | SAINTexpress; Cytoscape; GO (3) enrichment analysis. | Vesicle-mediated transport, Golgi vesicle transport, ER to Golgi vesicle-mediated transport, response to ER stress, retrograde transport endosome to Golgi, lipid biosynthetic process, ER organization, retrograde vesicle-mediated transport, COPII-coated vesicle budding. | All virus MS data available at https://massive.ucsd.edu |
Laurent et al. [24] | Stably transfected HEK-293 cells | BioID: BirA* enzyme fused separately at both N- and C- terminus of each bait, modified proteins purification followed by MS. | ToppCluster; Metascape; GO (3) enrichment analysis. | Innate immune response, autophagy, apoptosis, lipid metabolism, vesicular transport, chromatin remodeling, mRNA processing, inflammation, viral signal transduction, nucleic acid processing, cell adhesion and migration, platelet activation, coagulation regulation, olfactory receptors homeostasis and olfactory cell signal transmission. | Data exploitation available at http://www.sars-cov-2-interactome.org/ |
Viral Bait | AP-MS Article | Cellular Preys Identified by AP-MS in at Least Two Different Reports | Preys Found Also by Proximity Labeling | AP-MS/BioID | ||
---|---|---|---|---|---|---|
Laurent et al. [24] | Samavarchi-Tehrani et al. [22] | St-Germain et al. [23] | ||||
E | Gordon et al. [17] | No common interactors | N/A | N/A | N/A | N/A |
Stukalov et al. [21] | ||||||
M | Gordon et al. [17] | ATP1B1, COQ8B, INTS4, PITRM1, PMPCB, REEP5, RTN4 | REEP5, RTN4 | ATG9A, ATP1B1, REEP5, RTN4 | PMPCB | ATG9AATP1B1, PMPCB, REEP5, RTN4 |
Stukalov et al. [21] | ARFGEF2, ATG9A, COQ8B, INTS4, PITRM1, PMPCB, RTN4, | |||||
Li et al. [20] | ARFGEF2, ATG9A, ATP1B1, REEP5 | |||||
N | Gordon et al. [17] | G3BP1, G3BP2 | CAVIN1, G3BP1, G3BP2, | CAVIN1, G3BP1, G3BP2, | Viral bait not tested | CAVIN1 G3BP1, G3BP2, |
Stukalov et al. [21] | CAVIN1, G3BP1, G3BP2 | |||||
Li et al. [20] | CAVIN1, G3BP1, G3BP2 | |||||
S | Gordon et al. [17] | GOLGA7, ZDHHC5 | ZDHHC5 | ZDHHC5 | No common interactors | ZDHHC5 |
Stukalov et al. [21] | GOLGA7, ZDHHC5 | |||||
Li et al. [20] | No common interactors | |||||
ORF3a | Gordon et al. [17] | ALG5, ARL6IP6, CLCC1, HMOX1, TRIM59, VPS11; VPS-39 | CLCC1, CPD, HMOX2, VPS39 | CLCC1, CPD, RAB13, RAB14, TBL2, VPS39 | CLCC1, VPS-39, | CLCC1 CPD, HMOX2, RAB13, RAB14, TBL2VPS39 |
Stukalov et al. [21] | CLCC1, CPD, HMOX2, PROCR, RAB13, RAB14, SUMF2, TBL2, VPS11; VPS-39 | |||||
Li et al. [20] | ALG5, ARL6IP6, CLCC1, CPD, HMOX1, HMOX2, PROCR, RAB13, RAB14, SUMF2, TBL2, TRIM59, VPS-39 | |||||
ORF6 | Gordon et al. [17] | RAE1 | RAE1 | RAE1 | RAE1 | RAE1 |
Stukalov et al. [21] | No interactors identified for this bait | |||||
Li et al. [20] | RAE1 | |||||
ORF7a | Gordon et al. [17] | MDN1 | No common interactors | No common interactors | No common interactors | N/A |
Stukalov et al. [21] | ATR, MDN1 | |||||
Li et al. [20] | ATR | |||||
ORF8 | Gordon et al. [17] | GGH, NPTX1, UGGT2 | CNNM3 | CNNM3, GGH, NPTX1, UGGT2, | CNNM3 | GGH, NPTX1, UGGT2, CNNM3 |
Stukalov et al. [21] | CNNM3, GGH, NPTX1, UGGT2 | |||||
Li et al. [20] | CNNM3 | |||||
ORF9b | Gordon et al. [17] | TOMM70 | TOMM70 | TOMM70 | TOMM70 | TOMM70 |
Stukalov et al. [21] | TOMM70 | |||||
Nsp1 | Gordon et al. [17] | No common interactors | N/A | N/A | Viral bait not tested | N/A |
Stukalov et al. [21] | ||||||
Li et al. [20] | ||||||
Nsp2 | Gordon et al. [17] | GIGYF2, RAP1GDS1 | RAP1GDS1 | RAP1GDS1, | No common interactors | RAP1GDS1 |
Stukalov et al. [21] | RAP1GDS1 | |||||
Li et al. [20] | FOXK1, GIGYF2, RAP1GDS1 | |||||
Davies et al. [19] | FOXK1 | |||||
Nsp3 | Stukalov et al. [21] | No common interactors | N/A | N/A | N/A | N/A |
Li et al. [20] | ||||||
Nsp4 | Gordon et al. [17] | No common interactors | HSPA5 | No common interactors | HSPA5 | HSPA5 |
Stukalov et al. [21] | HSPA5 | |||||
Li et al. [20] | No common interactors | |||||
Davies et al. [19] | HSPA5 | |||||
Nsp5 | Gordon et al. [17] | No common interactors | N/A | N/A | Viral bait not tested | N/A |
Li et al. [20] | ||||||
Nsp6 | Gordon et al. [17] | ATP6AP1, ATP13A3, SIGMAR1 | ATP6AP1, SIGMAR1, | ATP6AP1 | ATP6AP1 | ATP6AP1, SIGMAR1 |
Stukalov et al. [21] | ATP6AP1, ATP13A3, SIGMAR1 | |||||
Nsp7 | Gordon et al. [17] | No common interactors | N/A | N/A | Viral bait not tested | N/A |
Stukalov et al. [21] | ||||||
Nsp8 | Gordon et al. [17] | ATE1, HECTD1 | HECTD1, HERC1 | HECTD1, HERC1 | Viral bait not tested | HECTD1 HERC1 |
Stukalov et al. [21] | ATE1, HERC1 | |||||
Li et al. [20] | HECTD1, HERC1 | |||||
Nsp9 | Gordon et al. [17] | EIF4H, GTF2F2, SPART | GTF2F2 | No common interactors | Viral bait not tested | GTF2F2 |
Stukalov et al. [21] | GTF2F2 | |||||
Li et al. [20] | EIF4H, GTF2F2, SPART | |||||
Nsp10 | Gordon et al. [17] | No common interactors | N/A | N/A | Viral bait not tested | N/A |
Stukalov et al. [21] | ||||||
Li et al. [20] | ||||||
Nsp12 | Gordon et al. [17] | No common interactors | N/A | N/A | Viral bait not tested | N/A |
Stukalov et al. [21] | ||||||
Nsp13 | Gordon et al. [17] | No common interactors | N/A | N/A | Viral bait not tested | N/A |
Stukalov et al. [21] | ||||||
Li et al. [20] | ||||||
Nsp14 | Gordon et al. [17] | SIRT5 | SIRT5 | No common interactors | Viral bait not tested | SIRT5 |
Stukalov et al. [21] | No common interactors | |||||
Li et al. [20] | SIRT5 | |||||
Nsp15 | Gordon et al. [17] | No common interactors | N/A | N/A | Viral bait not tested | N/A |
Stukalov et al. [21] | ||||||
Li et al. [20] | ||||||
Nsp16 | Gordon et al. [17] | Viral bait not tested | CCDC22 | No common interactors | Viral bait not tested | CCDC22 |
Stukalov et al. [21] | No common interactors | |||||
Li et al. [20] | CCDC22 | |||||
Gordon et al. [18] | CCDC22 |
Viral Proteins | Gordon et al. [17,18] | Stukalov et al. [21] | Li et al. [20] | Davies et al. [19] | Laurent et al. [24] | Samavarchi-Tehrani et al. [22] | St-Germain et al. [23] | |
---|---|---|---|---|---|---|---|---|
1 | M | ✓ | ✓ | ✓ | - | ✓ | ✓ | ✓ |
2 | N | ✓ | ✓ | ✓ | - | ✓ | ✓ | - |
3 | E | ✓ | ✓ | - | - | ✓ | ✓ | ✓ |
4 | S | ✓ | ✓ | ✓ | - | ✓ | ✓ | ✓ |
5 | ORF3a | ✓ | ✓ (referred as ORF3) | ✓ | - | ✓ | ✓ | ✓ |
6 | ORF3b | ✓ | - | - | - | ✓ | ✓ | ✓ |
7 | ORF6 | ✓ | ✓ | ✓ | - | ✓ | ✓ | ✓ |
8 | ORF7a | ✓ | ✓ | ✓ | - | ✓ | ✓ | ✓ |
9 | ORF7b | - | ✓ | - | - | ✓ | ✓ | ✓ |
10 | ORF8 | ✓ | ✓ | ✓ | - | ✓ | ✓ | ✓ |
11 | ORF9b | ✓ | ✓ | - | - | ✓ | ✓ | ✓ |
12 | ORF10 | ✓ | - | - | - | ✓ | - | - |
13 | ORF14 | ✓(referred as ORF9c) | - | - | - | ✓ | ✓ | - |
14 | Nsp1 | ✓ | ✓ | ✓ | - | ✓ | ✓ | - |
15 | Nsp2 | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ |
16 | Nsp3 | - | ✓ | ✓ | - | ✓ | ✓ | ✓ |
17 | Nsp4 | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ |
18 | Nsp5 | ✓ | - | ✓ | - | ✓ | ✓ | - |
19 | Nsp6 | ✓ | ✓ | - | - | ✓ | ✓ | ✓ |
20 | Nsp7 | ✓ | ✓ | - | - | ✓ | ✓ | - |
21 | Nsp8 | ✓ | ✓ | ✓ | - | ✓ | ✓ | - |
22 | Nsp9 | ✓ | ✓ | ✓ | - | ✓ | ✓ | - |
23 | Nsp10 | ✓ | ✓ | ✓ | - | ✓ | ✓ | - |
24 | Nsp11 | ✓ | - | - | - | - | - | - |
25 | Nsp12 | ✓ | ✓ | - | - | ✓ | ✓ | - |
26 | Nsp13 | ✓ | ✓ | ✓ | - | ✓ | ✓ | - |
27 | Nsp14 | ✓ | ✓ | ✓ | - | ✓ | ✓ | - |
28 | Nsp15 | ✓ | ✓ | ✓ | - | ✓ | ✓ | - |
29 | Nsp16 | ✓ | ✓ | ✓ | - | ✓ | ✓ | - |
TOT | 27 | 24 | 19 | 2 | 28 | 27 | 14 |
Drug | Chemical Structure | Mechanism of Action | SARS-CoV-2 PPI | Studies Which Detected Virus–Host PPI | In Vitro SARS-CoV-2 Antiviral Effects | In Vivo SARS-CoV-2 Activity |
---|---|---|---|---|---|---|
Chlorpromazine FDA approved | Ligand of Sigma-1 receptor | Nsp6-Sigma-1 (1) | Gordon et al. [17] Stukalov et al. [21] Laurent et al. [24] | A549-ACE2 pIC50 = 6.05 | Reduced requirement to mechanical ventilation (2) | |
Fluphenazine FDA approved | Ligand of Sigma-1 receptor | Nsp6-Sigma-1 (1) | Gordon et al. [17] Stukalov et al. [21] Laurent et al. [24] | A549-ACE2 pIC50 = 6.46 | Reduced requirement to mechanical ventilation (2) | |
Haloperidol FDA approved | Ligand of Sigma-1 receptor | Nsp6-Sigma-1 (1) | Gordon et al. [17] Stukalov et al. [21] Laurent et al. [24] | A549-ACE2 pIC50 = 5.68 | Reduced requirement to mechanical ventilation (2) | |
Indomethacin FDA approved | PGES-2 inhibitor | Nsp7-PGES-2 (3) | Gordon et al. [17] Gordon et al. [18] | A549-ACE2 pIC50 = 4.25 | Reduced hospitalization (4) | |
Ipatasertib compound in clinical trial | AKT inhibitor a potential kinase phosphorylating SARS-CoV-2 protein N | N-M (5) and M-AKT (6) kinase | (5) Li et al. [20] (6) Laurent et al. [24] | A549-ACE2 5 μM | N/A |
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Terracciano, R.; Preianò, M.; Fregola, A.; Pelaia, C.; Montalcini, T.; Savino, R. Mapping the SARS-CoV-2–Host Protein–Protein Interactome by Affinity Purification Mass Spectrometry and Proximity-Dependent Biotin Labeling: A Rational and Straightforward Route to Discover Host-Directed Anti-SARS-CoV-2 Therapeutics. Int. J. Mol. Sci. 2021, 22, 532. https://doi.org/10.3390/ijms22020532
Terracciano R, Preianò M, Fregola A, Pelaia C, Montalcini T, Savino R. Mapping the SARS-CoV-2–Host Protein–Protein Interactome by Affinity Purification Mass Spectrometry and Proximity-Dependent Biotin Labeling: A Rational and Straightforward Route to Discover Host-Directed Anti-SARS-CoV-2 Therapeutics. International Journal of Molecular Sciences. 2021; 22(2):532. https://doi.org/10.3390/ijms22020532
Chicago/Turabian StyleTerracciano, Rosa, Mariaimmacolata Preianò, Annalisa Fregola, Corrado Pelaia, Tiziana Montalcini, and Rocco Savino. 2021. "Mapping the SARS-CoV-2–Host Protein–Protein Interactome by Affinity Purification Mass Spectrometry and Proximity-Dependent Biotin Labeling: A Rational and Straightforward Route to Discover Host-Directed Anti-SARS-CoV-2 Therapeutics" International Journal of Molecular Sciences 22, no. 2: 532. https://doi.org/10.3390/ijms22020532