Table 1 |.
Twenty-eight of the 65 druggable control hubs (in Table S4) within no more than two steps away from SARS-Cov-2 proteins in the triple-layer PPI network. Shown are the druggable control hub (the Host Protein column), engaging Viral Protein (and the [Distance] between the host and viral proteins), Host Protein Function, and Targeting Drugs (and the Total number of drugs targeting the protein). Drugs are grouped based on their function categories marked in color. Drugs in orange correspond to immune-related agents, in green are dietary supplements, and in blue are gonadal hormones. The seven druggable control hubs discussed in the text are marked in grey. At least two drugs target the rest 21 druggable control hubs.
| Host Protein |
Viral Protein [Distance] |
Host Protein Function | Targeting Drugs (Total number) |
|---|---|---|---|
| RIPK1 | nsp12[1] | Inflammation, cell death, pathogen recognition | Fostamatinib |
| CYB5R3 | nsp7[1], orf9c[2], M[2] | Cholesterol biosynthetic process. | NADH, Flavin adenine dinucleotide, Copper |
| COMT | nsp7[1] | Neurotransmitter catabolic process | Conjugated estrogens, Diethylstilbestrol, Tolcapone (15) |
| SLC10A1 | nsp7[2], orf8[2], orf3a[2], M[2] | Bile acid and bile salt transport | Conjugated estrogens, Progesterone, Indomethacin, Cyclosporine A (CsA) (18) |
| SLC10A6 | nsp7[2], orf8[2] |
Transmembrane transport | Pregnenolone, Prasterone sulfate |
| MUC1 | nsp7[2], orf9c[2], orf8[2] |
Forming protective mucous barriers on epithelial surfaces | Fostamatinib, Potassium nitrate, TG4010 |
| TTPA | orf8[2], nsp13[2] |
Vitamin E metabolic process | Vitamin E supplements (6) |
| OPRM1 | orf8[2] | A class of opioid receptors | Tramadol, Morphine, Codeine (47) |
| TSPO | orf8[2] | Steroid hormone synthesis, immune response | Lorazepam, Temazepam, Alprazolam (12) |
| GLUL | orf8[2] | Ammonia and glutamate detoxification, acid-base homeostasis | Pegvisomant, L-Glutamine, Methionine (8) |
| IMPDH1 | nsp14[2] | Regulate cell growth | NADH, Ribavirin, Mycophenolate mofetil (7) |
| S100A13 | orf8[2] | Cell cycle progression and differentiation | Calcium (7) |
| RARA | orf8[2] | Regulation of differentiation of clock genes. | Adapalene, Acitretin, Alitretinoin (7) |
| MAPK1 | nsp13[2] | Differentiation, transcription regulation | Isoprenaline, Arsenic trioxide (6) |
| SLC16A2 | nsp7[2] | Transporter of thyroid hormone | Pyruvic acid, Tyrosine, L-Leucine (6) |
| CDK4 | nsp13[2] | Cell cycle progression | Fostamatinib, Palbociclib, Ribociclib, Abemaciclib |
| HDAC4 | nsp13[2] | Transcriptional regulation, cell cycle progression | Zinc, Romidepsin (4) |
| PEF1 | M[2] | Response to calcium ion | Calcium (3) |
| CATSPER1 | M[2] | Calcium ion transport | Calcium (3) |
| GNMT | orf8[2] | Methionine metabolic process | Ademetionine, Glycine, Citric acid |
| PCYT1A | orf8[2] | Regulation of phosphatidylcholine biosynthesis. | Choline, Lamivudine, Choline salicylate |
| SLC7A1 | nsp7[2] | Involved in amino acid transport. | L-Lysine, L-Arginine, Ornithine |
| YES1 | nsp13[2] | Innate immune response; transmembrane receptor protein | Fostamatinib, Dasatinib |
| ASPH | orf8[2] | Calcium ion transmembrane transport | Aspartic acid, Succinic acid |
| MAT2A | nsp9[2] | Catalyzes the production of AdoMet | Ademetionine, Methionine |
| PCNA | nsp15[2] | Positive regulation of DNA | Liothyronine, Acetylsalicylic acid |
| repair | |||
| SRR | nsp15[2] | Catalyzes the synthesis of D-serine from L-serine. | Pyridoxal phosphate, Serine |
| SULT2B1 | nsp8[2] | Catalyze sulfate conjugation of many hormones, and drugs. | Prasterone, Pregnenolone |