Human functional modules for drug repurposing against SARS-CoV-2
CoREx - The COVID-19 Repositioning Explorer
Suzana Santos, Mateo Torres, Diego Galeano, María del Mar Sánchez, Luca Cernuzzi, Alberto Paccanaro
This tool has been published in Cell Patterns, please cite: Machine learning and network medicine approaches for drug repositioning for COVID-19
We present FDA approved drugs and their targets in the context of human functional modules containing SARS-CoV-2 host proteins [1] – these are 332 human proteins that have been experimentally identified to bind to viral proteins during infection.
What we did:
- We predicted functional similarities between proteins by combining five types of experimental interactions (neighborhood, coexpression, experiments, database, textmining) from the STRING database [2] together with information from InterPro [3].
- We then created a human functional interactome, where each node is a protein and two proteins are connected if they are predicted to be functionally related.
- We identified functionally coherent modules by clustering this network using ClusterONE [4].
- Finally, we selected functional modules that include at least one SARS-CoV-2 host protein and one drug target retrieved from DrugBank [5].
Selecting a drug from the list below will take you to a page containing the functional modules that are hit by that drug and contain at least one SARS-CoV-2 host proteins.
For each functional module we include:
- A list of drugs that target proteins in the same module with their respective ATC categories.
- Connectivity Map scores for each drug from the Broad Institute [6] when available.
- For each drug, information on whether it is currently on clinical trials from ClinicalTrials.gov when this is available.
- GO functional enrichment for every predicted module, calculated using Enrichr [7].
References
1.
Gordon, D. E. et al. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature 1–13 (2020) doi:10.1038/s41586-020-2286-9.
2.
Szklarczyk, D. et al. STRING v11: protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res 47, D607–D613 (2019).
3.
Mitchell, A. L. et al. InterPro in 2019: improving coverage, classification and access to protein sequence annotations. Nucleic Acids Res 47, D351–D360 (2019).
4.
Nepusz, T., Yu, H. & Paccanaro, A. Detecting overlapping protein complexes in protein-protein interaction networks. Nature Methods 9, 471–472 (2012).
5.
Wishart, D. S. et al. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res 46, D1074–D1082 (2018).
6.
Subramanian, A. et al. A Next Generation Connectivity Map: L1000 Platform and the First 1,000,000 Profiles. Cell 171, 1437-1452.e17 (2017).
7.
Kuleshov, M. V. et al. Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res 44, W90–W97 (2016).
Copper (DB09130)
17 modulesFostamatinib (DB12010)
14 modulesNADH (DB00157)
14 modulesFlavin adenine dinucleotide (DB03147)
10 modulesCannabidiol (DB09061)
9 modulesZinc (DB01593)
8 modulesResveratrol (DB02709)
8 modulesZinc acetate (DB14487)
7 modulesZinc chloride (DB14533)
7 modulesSulfasalazine (DB00795)
7 modulesValproic acid (DB00313)
6 modulesAcetylsalicylic acid (DB00945)
5 modulesGlycerin (DB09462)
5 modulesPyridoxal phosphate (DB00114)
4 modulesDexibuprofen (DB09213)
4 modulesGlyburide (DB01016)
4 modulesIcosapent (DB00159)
4 modulesOmega-3-carboxylic acids (DB09568)
4 modulesTrimetazidine (DB09069)
4 modulesAlbendazole (DB00518)
4 modulesMebendazole (DB00643)
4 modulesRomidepsin (DB06176)
4 modulesGlutamic acid (DB00142)
3 modulesTheophylline (DB00277)
3 modulesMesalazine (DB00244)
3 modulesIbuprofen (DB01050)
3 modulesAntithymocyte immunoglobulin (rabbit) (DB00098)
3 modulesAdemetionine (DB00118)
3 modulesTriflusal (DB08814)
3 modulesCysteine (DB00151)
3 modulesPravastatin (DB00175)
3 modulesLovastatin (DB00227)
3 modulesSimvastatin (DB00641)
3 modulesAtorvastatin (DB01076)
3 modulesFluvastatin (DB01095)
3 modulesAbciximab (DB00054)
3 modulesEptifibatide (DB00063)
3 modulesLevothyroxine (DB00451)
3 modulesLevocarnitine (DB00583)
3 modulesTirofiban (DB00775)
3 modulesAcetaminophen (DB00316)
3 modulesIndomethacin (DB00328)
3 modulesMinoxidil (DB00350)
3 modulesNabumetone (DB00461)
3 modulesKetorolac (DB00465)
3 modulesTenoxicam (DB00469)
3 modulesTolmetin (DB00500)
3 modulesVincristine (DB00541)
3 modulesPiroxicam (DB00554)
3 modulesFenoprofen (DB00573)
3 modulesDiclofenac (DB00586)
3 modulesSulindac (DB00605)
3 modulesDiethylcarbamazine (DB00711)
3 modulesFlurbiprofen (DB00712)
3 modulesEtodolac (DB00749)
3 modulesMefenamic acid (DB00784)
3 modulesNaproxen (DB00788)
3 modulesRibavirin (DB00811)
3 modulesPhenylbutazone (DB00812)
3 modulesMeloxicam (DB00814)
3 modulesCarprofen (DB00821)
3 modulesDiflunisal (DB00861)
3 modulesSuprofen (DB00870)
3 modulesSalicylic acid (DB00936)
3 modulesMeclofenamic acid (DB00939)
3 modulesBromfenac (DB00963)
3 modulesOxaprozin (DB00991)
3 modulesKetoprofen (DB01009)
3 modulesBalsalazide (DB01014)
3 modulesPerhexiline (DB01074)
3 modulesPodofilox (DB01179)
3 modulesAminophylline (DB01223)
3 modulesLumiracoxib (DB01283)
3 modulesOxtriphylline (DB01303)
3 modulesSalsalate (DB01399)
3 modulesCholine magnesium trisalicylate (DB01401)
3 modulesAntrafenine (DB01419)
3 modulesAntipyrine (DB01435)
3 modulesTiaprofenic acid (DB01600)
3 modulesFlufenamic acid (DB02266)
3 modulesVorinostat (DB02546)
3 modulesMetamizole (DB04817)
3 modulesLornoxicam (DB06725)
3 modulesAceclofenac (DB06736)
3 modulesCabazitaxel (DB06772)
3 modulesNepafenac (DB06802)
3 modulesTixocortol (DB09091)
3 modulesLoxoprofen (DB09212)
3 modulesTolfenamic acid (DB09216)
3 modulesPhenyl salicylate (DB11071)
3 modulesTrolamine salicylate (DB11079)
3 modulesMenthyl salicylate (DB11201)
3 modulesGlycol salicylate (DB11323)
3 modulesBufexamac (DB13346)
3 modulesBendazac (DB13501)
3 modulesAcemetacin (DB13783)
3 modulesGlutathione (DB00143)
2 modulesGlycine (DB00145)
2 modulesDrotrecogin alfa (DB00055)
2 modulesAscorbic acid (DB00126)
2 modulesZonisamide (DB00909)
2 modulesAcetylcysteine (DB06151)
2 modulesAntihemophilic factor, human recombinant (DB00025)
2 modulesLonoctocog alfa (DB13998)
2 modulesMoroctocog alfa (DB13999)
2 modulesArsenic trioxide (DB01169)
2 modulesTroglitazone (DB00197)
2 modulesMetamfetamine (DB01577)
2 modulesReserpine (DB00206)
2 modulesProcaine (DB00721)
2 modulesPalmitic Acid (DB03796)
2 modulesTenecteplase (DB00031)
2 modulesFludarabine (DB01073)
2 modulesCitric acid (DB04272)
2 modulesAspartic acid (DB00128)
2 modulesAmiloride (DB00594)
2 modulesDisulfiram (DB00822)
2 modulesDasatinib (DB01254)
2 modulesVinblastine (DB00570)
2 modulesAdenine (DB00173)
2 modulesCarmustine (DB00262)
2 modulesTolcapone (DB00323)
2 modulesRifabutin (DB00615)
2 modulesMinaprine (DB00805)
2 modulesGlutathione disulfide (DB03310)
2 modulesNialamide (DB04820)
2 modulesOpicapone (DB11632)
2 modulesPemetrexed (DB00642)
2 modulesMethyldopa (DB00968)
2 modulesMercaptopurine (DB01033)
2 modulesAdenosine phosphate (DB00131)
2 modulesPhosphatidyl serine (DB00144)
2 modulesAmphetamine (DB00182)
2 modulesCarbidopa (DB00190)
2 modulesPhentermine (DB00191)
2 modulesMycophenolate mofetil (DB00688)
2 modulesTranylcypromine (DB00752)
2 modulesMycophenolic acid (DB01024)
2 modulesSelegiline (DB01037)
2 modulesPioglitazone (DB01132)
2 modulesProcarbazine (DB01168)
2 modulesMoclobemide (DB01171)
2 modulesIsocarboxazid (DB01247)
2 modulesRasagiline (DB01367)
2 modulesProbucol (DB01599)
2 modulesPargyline (DB01626)
2 modulesBerberine (DB04115)
2 modulesHesperidin (DB04703)
2 modulesNomifensine (DB04821)
2 modulesZimelidine (DB04832)
2 modulesSafinamide (DB06654)
2 modulesFingolimod (DB08868)
2 modulesBenserazide (DB12783)
2 modulesMethoxyflurane (DB01028)
1 moduleHalothane (DB01159)
1 moduleSevoflurane (DB01236)
1 moduleIsoflurane (DB00753)
1 moduleDesflurane (DB01189)
1 moduleEnflurane (DB00228)
1 moduleCalcium (DB01373)
1 moduleHydroflumethiazide (DB00774)
1 moduleCalcium Citrate (DB11093)
1 moduleCalcium Phosphate (DB11348)
1 moduleCalcium phosphate dihydrate (DB14481)
1 moduleAminocaproic acid (DB00513)
1 moduleDiazoxide (DB01119)
1 moduleInsulin pork (DB00071)
1 moduleNatalizumab (DB00108)
1 moduleTrichlormethiazide (DB01021)
1 moduleCarvedilol (DB01136)
1 moduleMedroxyprogesterone acetate (DB00603)
1 moduleClove oil (DB11338)
1 moduleTasonermin (DB11626)
1 moduleUrokinase (DB00013)
1 moduleIloprost (DB01088)
1 moduleHuman C1-esterase inhibitor (DB06404)
1 moduleXanthinol (DB09092)
1 moduleConestat alfa (DB09228)
1 moduleCollagenase clostridium histolyticum (DB00048)
1 moduleDigoxin (DB00390)
1 moduleAcetyldigitoxin (DB00511)
1 moduleAlendronic acid (DB00630)
1 moduleEtacrynic acid (DB00903)
1 moduleDeslanoside (DB01078)
1 moduleOuabain (DB01092)
1 moduleBretylium (DB01158)
1 moduleCiclopirox (DB01188)
1 moduleBepridil (DB01244)
1 modulePotassium cation (DB01345)
1 moduleAluminium (DB01370)
1 moduleMagnesium cation (DB01378)
1 moduleDigitoxin (DB01396)
1 moduleAlmitrine (DB01430)
1 moduleTinzaparin (DB06822)
1 moduleMagnesium acetate (DB13996)
1 modulePotassium acetate (DB14498)
1 modulePotassium sulfate (DB14499)
1 moduleAluminium phosphate (DB14517)
1 moduleAluminum acetate (DB14518)
1 moduleIsopropyl alcohol (DB02325)
1 moduleCholic Acid (DB02659)
1 moduleVedolizumab (DB09033)
1 moduleTenapanor (DB11761)
1 moduleVonicog Alfa (DB12872)
1 moduleVon Willebrand Factor Human (DB13133)
1 moduleAlteplase (DB00009)
1 moduleReteplase (DB00015)
1 moduleAnistreplase (DB00029)
1 moduleCladribine (DB00242)
1 moduleClofarabine (DB00631)
1 moduleDacarbazine (DB00851)
1 moduleNelarabine (DB01280)
1 moduleBortezomib (DB00188)
1 moduleRosiglitazone (DB00412)
1 moduleBacitracin (DB00626)
1 moduleAzacitidine (DB00928)
1 moduleProcainamide (DB01035)
1 moduleEtidronic acid (DB01077)
1 moduleFlucytosine (DB01099)
1 moduleTiludronic acid (DB01133)
1 moduleDecitabine (DB01262)
1 moduleOmacetaxine mepesuccinate (DB04865)
1 moduleGallium nitrate (DB05260)
1 moduleHyaluronic acid (DB08818)
1 moduleCarfilzomib (DB08889)
1 moduleUbidecarenone (DB09270)
1 moduleThimerosal (DB11590)
1 moduleHydroxocobalamin (DB00200)
1 moduleMetformin (DB00331)
1 moduleEzetimibe (DB00973)
1 moduleDopamine (DB00988)
1 moduleOrlistat (DB01083)
1 moduleFomepizole (DB01213)
1 moduleCapsaicin (DB06774)
1 moduleSilver (DB12965)
1 moduleIron (DB01592)
1 moduleFerrous gluconate (DB14488)
1 moduleFerrous succinate (DB14489)
1 moduleFerrous ascorbate (DB14490)
1 moduleFerrous fumarate (DB14491)
1 moduleFerrous glycine sulfate (DB14501)
1 moduleStreptokinase (DB00086)
1 moduleL-Glutamine (DB00130)
1 moduleMethionine (DB00134)
1 moduleTranexamic acid (DB00302)
1 moduleMelatonin (DB01065)
1 moduleAprotinin (DB06692)
1 moduleThonzonium (DB09552)
1 moduleCyanocobalamin (DB00115)
1 moduleBiotin (DB00121)
1 moduleVinorelbine (DB00361)
1 moduleGemcitabine (DB00441)
1 moduleFluoxetine (DB00472)
1 moduleNedocromil (DB00716)
1 modulePentamidine (DB00738)
1 moduleRoxithromycin (DB00778)
1 moduleAzathioprine (DB00993)
1 moduleDoxorubicin (DB00997)
1 moduleIsoprenaline (DB01064)
1 moduleEpoprostenol (DB01240)
1 moduleColchicine (DB01394)
1 module5-O-phosphono-alpha-D-ribofuranosyl diphosphate (DB01632)
1 moduleNicotinamide (DB02701)
1 moduleRibostamycin (DB03615)
1 moduleDabrafenib (DB08912)
1 moduleMiltefosine (DB09031)
1 moduleTocofersolan (DB11635)
1 moduleVinflunine (DB11641)
1 moduleCurcumin (DB11672)
1 moduleAvatrombopag (DB11995)
1 moduleTelotristat ethyl (DB12095)
1 module