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Table S1. Characteristics of Repurposed Drugs/Compounds for Control of Fungal Pathogens. 1 Compounds Original Functions Target F

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Table S1. Characteristics of Repurposed Drugs/Compounds for Control of Fungal Pathogens. 1 Compounds Original Functions Target F Table S1. Characteristics of repurposed drugs/compounds for control of fungal pathogens. 1 Repurposing methods; Compounds Original functions Target fungi References cellular processes affected A. IN SILICO, COMPUTATIONAL Computational chemogenomics; Vistusertib, Anti-neoplastic drug Paracoccidioides species fungal phosphatidylinositol 3-kinase [15] BGT-226 candidates (TOR2) Candida albicans, Candida glabrata, Candida tropicalis, Candida dubliniensis, Candida parapsilosis, Aspergillus fumigatus, Aspergillus flavus, Rhizopus oryzae, Rhizopus microspores, Rhizomucor pusillus, Computational, Docking fluvastatin Rhizomucor miehei, Mucor racemosus, with cytochrome P450 (CYP51) Fluvastatin Anti-high cholesterol & [18,19] Mucor mucedo, Mucor circinelloides, model; triglycerides (blood) Absidia corymbifera, Absidia glauca, inhibition of growth and biofilm Trichophyton mentagrophytes, formation Trichophyton rubrum, Microsporum canis, Microsporum gypseum, Paecilomyces variotii, Syncephalastrum racemosum, Pythium insidiosum Ligand-based virtual screening, C. albicans, C. parapsilosis, Plant chorismate mutase homology modelling, molecular [16] Abscisic acid Aspergillus niger, inhibitor docking; T. rubrum, Trichophyton mentagrophytes chorismate mutase Homology modeling and molecular docking; P. insidiosum, Candida species, putative aldehyde dehydrogenase Disulfiram Treatment of alcoholism Cryptococcus species, A. fumigatus, [17,22] and urease activities, Histoplasma capsulatum bind/inactivate multiple proteins of P. insidiosum Raltegravir (MDDR, In silico ligand-based, molecular DrugBank, Antiviral drug Paracoccidioides species docking, murine assay; [20] TargetMol thioredoxin reductase databases) 1 Killing kinetics assay, post- Sertraline Anti-depression drug Candida auris antifungal effect; in silico docking; [21] inhibit ergosterol biosynthesis B. EXPERIMENTAL, DRUG SYNERGISM Candida species, Cryptococcus species, Trifluoperazine, Saccharomyces cerevisiae, 2 CLSI; gene-drug network tamoxifen, Psychiatric medication, Lomentospora prolificans, interactions analysis; clomiphene, estrogen modulator, Curvularia lunata, Curvularia geniculata, species- or genus-specific synergism sertraline, antidepressant, anti-platelet Curvularia spicifera, Alternaria alternata, with FLU, VOR, CAS or AMB; suloctidil, [23,24,29] aggregation, serine Fusarium incarnatum, Fusarium solani, perturbed membrane permeability L-cycloserine palmitoyl-transferase Fusarium verticillioides, Scedosporium boydii, or inhibited sphingolipid (Prestwick inhibitor Scedosporium apiospermum, biosynthesis Chemical Library) Purpureocillium lilacinum, Paecilomyces variottii, Trichosporon asahii C. auris, seven Candida species, CLSI M27-A3, P. variotii, Cryptococcus neoformans, Ebselen Anti-cardiovascular disease, synergism with FLU (C. albicans), Rhizopus arrhizus, A. fumigatus, (Prestwick arthritis, stroke, VOR (Fusarium species) or AMB [25-28] A. niger, Fusarium oxysporum, Chemical Library) atherosclerosis, cancer, etc. (Trichosporon asahii) F. solani, S. apiospermum, Lomentospora prolificans, T. asahii 3 EUCAST, synergism with VOR, Suloctidil, ITR, POS, MICO or anidulafungin; Pyrvinium Anti-cardiovascular disease, interaction with the plasma pamoate, arthritis, stroke, C. albicans, C. auris, membrane H+-ATPase, Ebselen atherosclerosis, cancer, etc., Exophiala dermatitidis [15,30,31,33,34] inhibition of membrane (Prestwick antiplatelet, trafficking, vacuolar biogenesis, Chemical Library) anthelmintic drugs biofilm inhibition & resistance management Bromperidol C. albicans, C. glabrata, Checkerboard bioassay, Antipsychotic drugs [32] derivatives Aspergillus terreus synergism with azoles High throughput synergistic screen Review: (HTSS) platform, Anti-virulence CLSI M38-A2; agents; resistance [39] Anti-virulence factors C. albicans targeting virulence factors (e.g., management, environmental adaptation factors, antifungal adhesins, morphogenesis, secreted repurposing enzymes, phenotype switching, 2 biofilms), antifungal synergistic drug combination database (ASDCD) Yeasts (Candida, Cryptococcus, Rhodotorula, Time-kill study, Malassezia pachydermatis, checkerboard assay; Exophiala dermatitidis synergism with polyenes & azoles, S. cerevisiae), Polymyxin B, colistin synergism with CAS, Antibiotics Molds (Aspergillus, Fusarium, [35-38,40-44] colistin polymyxin B: overcoming multidrug Scedosporium, Lichtheimia, Rhizopus, resistance, Geosmithia argillacea, synergism with Zwiebelane A in Zygomycetes), fungal vacuole disruption) Batrachochytrium salamandrivorans CLSI M27-A3; calmodulin inhibition, structural C. neoformans, C. albicans, scaffolds Tamoxifen Estrogen receptor modulator Schizosaccharomyces pombe (alkylamino group, aliphatic [46-48] substituent, electronegative substituents), synergism with AMB CLSI M27-A3, C. neoformans gene deletion library assay, macrophage assay, synergism Tamoxifen, Estrogen receptor antagonists C. neoformans with FLU; [49] Toremifene prevent calmodulin binding to calcineurin (Cna1), block Cna1 activation C. albicans, C. glabrata, Candida tropicalis, Candida krusei, Candida parapsilosis Candida utilis, S. cerevisiae, R. oryzae, T. mentagrophytes, T. rubrum, M. canis, M. gypseum, CLSI M-27A, A. flavus, A. fumigatus, A. terreus, synergism with ITR or AMB; Lovastatin Anti-cholesterol drug [45,50-59] A. niger, Paecilomyces variotii, inhibit ergosterol biosynthesis, Rhizopus stolonifer, Rhizopus homothallicus, planktonic cells and biofilms Mucor circinelloides, Mucor racemosus, Cunninghamella bertholletiae, Mortierella wolfii, Syncephalastrum racemosu, 3 Mycotypha africana EUCAST, macrophage test, C. neoformans, Cryptococcus gattii, antibiofilm, synergism of ibuprofen C. albicans, C. glabrata, C. krusei with FLU, ITR, ISA, C. parapsilosis, C. tropicalis, Anti-inflammatory drug, VOR, POS, CAS or AMB; Aspirin, Ibuprofen Candida guilliermondii, T. asahii, [60-64,67,69,70] blood thinners activation of the high-osmolarity Trichophyton mentagrophytes, glycerol pathway, reactive oxygen Epidermophyton floccosum, species-mediated membrane M. circinelloides damage Drospirenon, Perhexiline, Biofilm cell titer blue assay, Anti-anginal, Birth control, Toremifene C. albicans, C. glabrata checkerboard bioassay, [68] Estrogen receptor modulator (Pharmakon1600 synergism with AMB or CAS library) Erythromycin, Riluzole, Nortriptyline, Chenodiol, C. neoformans, Candida species Nisoldipine, Antibacterial drug, EUCAST-AFST E.DEF 7.3, (including C. utilis, C. krusei, C. glabrata) Promazine, Treatment of high blood synergism with AMB; [66,71,72,74] Pythium insidiosum, Chlorcyclizine, pressure, allergy, etc. anti-hyphal and biofilm activity Mycosphaerella graminicola Cloperastine, Glimepiride (Prestwick Chemical Library) Susceptibility testing, synergism with the calcineurin inhibitor FK506; Eltrombopag calcineurin pathway, (Compound lipid biosynthesis, Thrombopoietin receptor C. neoformans, C. gattii, [73] library of 1018 membrane component, agonist C. glabrata, T. rubrum FDA-approved transporter genes, drugs) capsule & biofilm formation, melanin production, growth ability at 37°C Thirty-one C. neoformans, Fusarium culmorum, CLSI M27-A2, murine phagocyte Anti-psychotic, Anti- drugs/molecules; Fusarium falciforme, Fusarium nelsonii, assay, synergism with FLU, VOR, depressant, [75,80] amiodarone, F. oxysporum, F. solani, CAS or AMB; Anti-estrogen, etc. thioridazine F. verticillioides calmodulin inhibition 4 (Prestwick Chemical Library) XTT (2,3-bis(2-methoxy-4-nitro-5- sulfo-phenyl)-2H-tetrazolium-5- FDA approved carboxanilide) assay, Amiodarone antiarrhythmic drug A. niger additive to synergistic to AMB, [76] CLO or KET; affects cellular calcium and pH homeostasis Pitavastatin Control of blood cholesterol C. albicans, C. glabrata, Biofilm inhibition assay, (Pharmakon 1600 [77] level C. auris synergism with FLU drug library) CLSI M-27A3, synergism with ITR, VOR or FLU; Haloperidol/ Efflux pump modulation, C. albicans, C. glabrata, inhibition of filamentation, melanin [78,79,81,82] Benzocyclane antipsychotics C. neoformans, Microsporum canis, production and biofilm formation, derivative Malassezia furfur, Malassezia pachydermatis overexpression of lanosterol 14a- demethylase (CYP51), Efflux pump expression bis-Biguanide alexidine dihydrochloride Anticancer drug that targets a Microtiter plate assay, synergism A. fumigatus, C. albicans, [83] (AXD) mitochondrial tyrosine with FLU against biofilms; C. auris (1200 New phosphatase antifungal, antibiofilm activity Prestwick Chemical Library) CLSI M-27A3, synergism with KET, FLU or MICO, cure the murine model of C. albicans, C. glabrata, disseminated candidiasis; Beauvericin [84-87,89] Antibiotic, insecticidal C. parapsilosis, C. neoformans, drug efflux pump modulation, A. fumigatus blocking the ATP-binding cassette transporters, elevating intracellular calcium and reactive oxygen species C. albicans (AMB resistant), C. dubliniensis Arachidonic acid Polyunsaturated fatty acid CLSI M27-A, synergism with FLU, C. parapsilosis, C. glabrata, [88,90] TER, CLO or AMB against biofilms; C. tropicalis 5 increase in production of prostaglandin CLSI M27-A2, adjunct therapy, Ribavirin synergism with azoles; A guanosine anti-viral agent (Prestwick Candida species fungistatic against multidrug- [94,95] against RNA or DNA virus Chemical Library) resistant C. albicans and fungicidal against C. parapsilosis Candida species, Cryptococcus species, Fonsecaea pedrosoi, Fonsecaea monophora, CLSI M27-A3, synergism with ITR Fonsecaea nubica, Cladophialophora carrionii,
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