Network Controllability-Based Prioritization of Candidates for SARS-CoV-2 Drug Repositioning
Abstract
:1. Introduction
2. Methods
2.1. Protein–Protein Interaction Network Construction
2.2. Robust Classification
2.3. Global Classification
3. Results
3.1. Topology of the Host Interaction Network and Virus Integrated Network
3.2. Driver Proteins
3.3. Robust Controllability
3.4. Global Controllability
3.5. Controllability-Guided Drug Targeting and Repurposing
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Entrez ID | Gene Name | Virus Interaction | IRG |
---|---|---|---|
3250 | haptoglobin-related protein (HPR) | - | X |
23225 | nucleoporin 210 (NUP210) | Nsp4 | X |
26505 | cyclin and CBS domain divalent metal cation transport mediator 3 (CNNM3) | - | X |
5557 | primase (DNA) subunit 1 (PRIM1) | Nsp1 | X |
23367 | La ribonucleoprotein domain family member 1 (LARP1) | N | X |
382 | ADP ribosylation factor 6 (ARF6) | Nsp15 | X |
2802 | golgin A3 (GOLGA3) | Nsp13 | X |
949 | scavenger receptor class B member 1 (SCARB1) | Nsp7 | X |
10280 | sigma non-opioid intracellular receptor 1 (SIGMAR1) | Nsp6 | |
84767 | tripartite motif-containing 51 (TRIM51) | - | X |
3615 | inosine monophosphate dehydrogenase 2 (IMPDH2) | Nsp14 | X |
9470 | eukaryotic translation initiation factor 4E family member 2 (EIF4E2) | Nsp2 | |
55823 | VPS11, CORVET/HOPS core subunit (VPS11) | ORF3a, ORF8 | X |
523 | ATPase H+ transporting V1 subunit A (ATP6V1A) | M | X |
2876 | glutathione peroxidase 1 (GPX1) | Nsp5_C145A | X |
23181 | disco interacting protein 2 homolog A (DIP2A) | - | X |
2150 | F2R like trypsin receptor 1 (F2RL1) | ORF9c | X |
5817 | poliovirus receptor (PVR) | ORF8 | X |
6731 | signal recognition particle 72 (SRP72) | Nsp8 | X |
4276 | MHC class I polypeptide-related sequence A (MICA) | - |
Indispensable | Neutral | Dispensable | Total | |
---|---|---|---|---|
All proteins | 1170 (1169) | 2675 (2658) | 2459 (2454) | 6304 (6281) |
18.6% (18.6%) | 42.4% (42.3%) | 39.0% (39.1%) | 100% | |
Driver proteins | 0 (0) | 810 (799) | 1656 (1664) | 2466 (2463) |
0% (0%) | 32.8% (32.4%) | 67.2% (67.6%) | 100% | |
Virus interacting proteins | 32 (30) | 57 (57) | 59 (61) | 148 (148) |
21.6% (20.3%) | 38.5% (38.5%) | 39.8% (41.2%) | 100% |
Entrez ID | Gene Name | Degree | Betweenness | Classification | IRG |
---|---|---|---|---|---|
1174 | adaptor-related protein complex 1 sigma 1 subunit (AP1S1) | 3 (3) | 34.1 (33.0) | D (N) | |
3615 | inosine monophosphate dehydrogenase 2(IMPDH2) | 4 (3) | 4090.0 (65.0) | N (D) | X |
6993 | dynein light chain Tctex-type 1(DYNLT1) | 11 (11) | 44,093.7 (43,902.7) | D (N) | X |
8480 | ribonucleic acid export 1(RAE1) | 6 (5) | 3863.3 (1076.3) | I (N) | |
10280 | sigma non-opioid intracellular receptor 1(SIGMAR1) | 3 (2) | 4094.0 (0.0) | I (N) | |
10987 | COP9 signalosome subunit 5(COPS5) | 33 (33) | 30,094.4 (29,968.0) | N (I) | |
23225 | nucleoporin 210(NUP210) | 4 (3) | 331.1 (325.9) | N (D) | |
64326 | ring finger and WD repeat domain 2(RFWD2) | 3 (3) | 207.1 (206.8) | D (N) | |
64837 | kinesin light chain 2(KLC2) | 7 (7) | 463.2 (460.3) | D (N) |
Critical | Intermittent | Redundant | Total | |
---|---|---|---|---|
All proteins | 540 (525) | 3322 (3318) | 2442 (2438) | 6304 (6281) |
8.6% (8.4%) | 52.7% (52.8%) | 38.7% (38.8%) | 100% | |
Driver proteins | 540 (525) | 1926 (1983) | 0 (0) | 2466 (2463) |
21.9% (21.3%) | 78.1% (80.5%) | 0% (0%) | 100% | |
Virus interacting proteins | 0 (8) | 79 (75) | 69 (65) | 148 (148) |
0% (5.4%) | 53.4% (50.7%) | 46.6% (32.9%) | 100% |
Entrez ID | Gene Name | Degree | Betweenness | Classification | IRG |
---|---|---|---|---|---|
949 | scavenger receptor class B member 1(SCARB1) | 5 (4) | 1098.0 (0.0) | I (C) | X |
3615 | inosine monophosphate dehydrogenase 2(IMPDH2) | 4 (3) | 4090.0 (65.0) | R (I) | X |
5817 | poliovirus receptor (PVR) | 7 (6) | 349.6 (0.0) | I (C) | X |
8480 | ribonucleic acid export 1(RAE1) | 6 (5) | 3863.3 (1076.3) | R (I) | X |
9470 | eukaryotic translation initiation factor 4E family member 2(EIF4E2) | 4 (3) | 672.1 (0.0) | I (C) | |
9662 | centrosomal protein 135(CEP135) | 2 (1) | 46.6 (0.0) | I (C) | X |
10280 | sigma non-opioid intracellular receptor 1(SIGMAR1) | 3 (2) | 4094.0 (0.0) | R (C) | |
23225 | nucleoporin 210(NUP210) | 4 (3) | 331.1 (325.9) | R (I) | X |
26092 | torsin 1A interacting protein 1(TOR1AIP1) | 2 (1) | 41.1 (0.0) | I (C) | X |
51552 | RAB14, member RAS oncogene family (RAB14) | 2 (1) | 1.0 (0.0) | I (C) | X |
113174 | serum amyloid A like 1(SAAL1) | 2 (1) | 78.2 (0.0) | I (C) |
Drug (Status) | Structure | Target/Viral Protein | Target Function |
---|---|---|---|
Myristic acid (Experimental) | | PVR/ORF8 | Regulate Natural killer cells, polio virus [27] |
Sphingosine (Experimental) | | ||
Phosphatidyl serine (Approved) | | SCARB1/Nsp7 | Facilitate cell entry, Hepatitis C [31] |
Tocopherol/Vitamin E (Approved) | | ||
PHA-665752 (Experimental) | | SCARB1/Nsp7 | Facilitate cell entry, Hepatitis C [31] |
NUP210/Nsp4 | Transport between nucleus and cytoplasm [32] |
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Ackerman, E.E.; Shoemaker, J.E. Network Controllability-Based Prioritization of Candidates for SARS-CoV-2 Drug Repositioning. Viruses 2020, 12, 1087. https://doi.org/10.3390/v12101087
Ackerman EE, Shoemaker JE. Network Controllability-Based Prioritization of Candidates for SARS-CoV-2 Drug Repositioning. Viruses. 2020; 12(10):1087. https://doi.org/10.3390/v12101087
Chicago/Turabian StyleAckerman, Emily E., and Jason E. Shoemaker. 2020. "Network Controllability-Based Prioritization of Candidates for SARS-CoV-2 Drug Repositioning" Viruses 12, no. 10: 1087. https://doi.org/10.3390/v12101087
APA StyleAckerman, E. E., & Shoemaker, J. E. (2020). Network Controllability-Based Prioritization of Candidates for SARS-CoV-2 Drug Repositioning. Viruses, 12(10), 1087. https://doi.org/10.3390/v12101087