{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T01:04:50Z","timestamp":1792631090227,"version":"4.5.0"},"reference-count":80,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T00:00:00Z","timestamp":1734307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES), Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)","doi-asserted-by":"publisher","award":["408964\/2018-9"],"award-info":[{"award-number":["408964\/2018-9"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES), Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)","doi-asserted-by":"publisher","award":["ADRC 09\/2019"],"award-info":[{"award-number":["ADRC 09\/2019"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Pr\u00f3-Reitoria de Pesquisa-Universidade Federal de Minas Gerais\u2014ADRC","award":["408964\/2018-9"],"award-info":[{"award-number":["408964\/2018-9"]}]},{"name":"Pr\u00f3-Reitoria de Pesquisa-Universidade Federal de Minas Gerais\u2014ADRC","award":["ADRC 09\/2019"],"award-info":[{"award-number":["ADRC 09\/2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Toxoplasma gondii is a protozoan, and the etiologic agent of toxoplasmosis, a disease that causes high mortality in immunocompromised individuals and newborns. Despite the medical importance of toxoplasmosis, few drugs, which are associated with side effects and parasite resistance, are available for its treatment. Here, we show a screening of molecules present in COVID-Box to discover new hits with anti-T. gondii activity. COVID-Box contains 160 molecules with known or predicted activity against SARS-CoV-2. Our analysis selected 23 COVID-Box molecules that can inhibit the tachyzoite forms of the RH strain of T. gondii in vitro by more than 70% at 1 \u00b5M after seven days of treatment. The inhibitory curves showed that most of these molecules inhibited the proliferation of tachyzoites with IC50 values below 0.80 \u00b5M; Cycloheximide and (-)-anisomycin were the most active drugs, with IC50 values of 0.02 \u03bcM. Cell viability assays showed that the compounds are not toxic at active concentrations, and most are highly selective for parasites. Overall, all 23 compounds were selective, and for two of them (apilimod and midostaurin), this is the first report of activity against T. gondii. To better understand the effect of the drugs, we analyzed the effect of nine of them on the ultrastructure of T. gondii using transmission electron microscopy. After treatment with the selected drugs, the main changes observed in parasite morphology were the arrestment of cell division and organelle alterations.<\/jats:p>","DOI":"10.3390\/microorganisms12122602","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T09:17:58Z","timestamp":1734340678000},"page":"2602","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Antiproliferative and Morphological Analysis Triggered by Drugs Contained in the Medicines for Malaria Venture COVID-Box Against Toxoplasma gondii Tachyzoites"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5870-2502","authenticated-orcid":false,"given":"Andr\u00e9ia Luiza Oliveira","family":"Costa","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Quimioterapia de Protozo\u00e1rios Egler Chiari, Departamento de Parasitologia\u2014ICB, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3884-0131","authenticated-orcid":false,"given":"Mike","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Quimioterapia de Protozo\u00e1rios Egler Chiari, Departamento de Parasitologia\u2014ICB, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6812-5764","authenticated-orcid":false,"given":"Giulia Caroline","family":"Dantas-Vieira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Quimioterapia de Protozo\u00e1rios Egler Chiari, Departamento de Parasitologia\u2014ICB, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ros\u00e1lida Estevam Nazar","family":"Lopes","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Quimioterapia de Protozo\u00e1rios Egler Chiari, Departamento de Parasitologia\u2014ICB, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4768-1555","authenticated-orcid":false,"given":"Rossiane Claudia","family":"Vommaro","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Ultraestrutura Celular Hertha Meyer, Instituto de Biof\u00edsica Carlos Chagas Filho, Centro de Pesquisa em Medicina de Precis\u00e3o, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0925-6953","authenticated-orcid":false,"given":"\u00c9rica S.","family":"Martins-Duarte","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Quimioterapia de Protozo\u00e1rios Egler Chiari, Departamento de Parasitologia\u2014ICB, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bigna, J.J., Tochie, J.N., Tounouga, D.N., Bekolo, A.O., Ymele, N.S., Youda, E.L., Sime, P.S., and Nansseu, J.R. (2020). Global, Regional, and Country Seroprevalence of Toxoplasma gondii in Pregnant Women: A Systematic Review, Modelling and Meta-Analysis. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-69078-9"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1128\/CMR.05013-11","article-title":"Epidemiology of and Diagnostic Strategies for Toxoplasmosis","volume":"25","year":"2012","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/BF00193846","article-title":"High Risk of Developing Toxoplasmic Encephalitis in AIDS Patients Seropositive to Toxoplasma gondii","volume":"180","author":"Zangerle","year":"1991","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.1016\/j.ophtha.2009.04.042","article-title":"Congenital Toxoplasmosis in Southeastern Brazil: Results of Early Ophthalmologic Examination of a Large Cohort of Neonates","volume":"116","author":"Campos","year":"2009","journal-title":"Ophthalmology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1136\/bjo.84.2.224","article-title":"Is Ocular Toxoplasmosis Caused by Prenatal or Postnatal Infection?","volume":"84","author":"Gilbert","year":"2000","journal-title":"Br. J. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Gilbert, R.E., Freeman, K., Lago, E.G., Bahia-Oliveira, L.M.G., Tan, H.K., Wallon, M., Buffolano, W., Stanford, M.R., and Petersen, E. (2008). For the European Multicentre Study on Congenital Toxoplasmosis (EMSCOT) Ocular Sequelae of Congenital Toxoplasmosis in Brazil Compared with Europe. PLoS Negl. Trop. Dis., 2.","DOI":"10.1371\/journal.pntd.0000277"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1097\/00006254-200105000-00025","article-title":"Congenital Toxoplasmosis: A Review","volume":"56","author":"Jones","year":"2001","journal-title":"Obstet. Gynecol. Surv."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1055\/s-0039-1697034","article-title":"Follow-up of Toxoplasmosis during Pregnancy: Ten-Year Experience in a University Hospital in Southern Brazil","volume":"41","author":"Diesel","year":"2019","journal-title":"Rev. Bras. Ginecol. Obs."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e00057-17","DOI":"10.1128\/CMR.00057-17","article-title":"Treatment of Toxoplasmosis: Historical Perspective, Animal Models, and Current Clinical Practice","volume":"31","author":"Dunay","year":"2018","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7161","DOI":"10.1128\/AAC.02009-15","article-title":"Clinically Available Medicines Demonstrating Anti-Toxoplasma Activity","volume":"59","author":"Neville","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Silva, L.A., Reis-Cunha, J.L., Bartholomeu, D.C., and V\u00edtor, R.W.A. (2017). Genetic Polymorphisms and Phenotypic Profiles of Sulfadiazine-Resistant and Sensitive Toxoplasma gondii Isolates Obtained from Newborns with Congenital Toxoplasmosis in Minas Gerais, Brazil. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0170689"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.exppara.2019.05.001","article-title":"Efficacy of Sulfadiazine and Pyrimetamine for Treatment of Experimental Toxoplasmosis with Strains Obtained from Human Cases of Congenital Disease in Brazil","volume":"202","author":"Silva","year":"2019","journal-title":"Exp. Parasitol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"De Lima Bessa, G., Vitor, R.W.D.A., Lobo, L.M.S., R\u00eago, W.M.F., De Souza, G.C.A., Lopes, R.E.N., Costa, J.G.L., and Martins-Duarte, E.S. (2023). In Vitro and in Vivo Susceptibility to Sulfadiazine and Pyrimethamine of Toxoplasma gondii Strains Isolated from Brazilian Free Wild Birds. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-34502-3"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.7150\/ijbs.24612","article-title":"Review of Drug Repositioning Approaches and Resources","volume":"14","author":"Xue","year":"2018","journal-title":"Int. J. Biol. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1111\/jphp.13273","article-title":"Drug Repositioning: A Brief Overview","volume":"72","author":"Jourdan","year":"2020","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5848","DOI":"10.1128\/AAC.02541-14","article-title":"Repurposing the Open Access Malaria Box To Discover Potent Inhibitors of Toxoplasma gondii and Entamoeba histolytica","volume":"58","author":"Boyom","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e00534-17","DOI":"10.1128\/mSphere.00534-17","article-title":"Targeted Phenotypic Screening in Plasmodium falciparum and Toxoplasma gondii Reveals Novel Modes of Action of Medicines for Malaria Venture Malaria Box Molecules","volume":"3","author":"Subramanian","year":"2018","journal-title":"mSphere"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e01489-17","DOI":"10.1128\/AAC.01489-17","article-title":"Characterization of Plasmodium Atg3-Atg8 Interaction Inhibitors Identifies Novel Alternative Mechanisms of Action in Toxoplasma gondii","volume":"62","author":"Varberg","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e01640-17","DOI":"10.1128\/AAC.01640-17","article-title":"Discovery of New Inhibitors of Toxoplasma gondii via the Pathogen Box","volume":"62","author":"Spalenka","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1021\/acsinfecdis.8b00113","article-title":"Evaluation of Current and Emerging Antimalarial Medicines for Inhibition of Toxoplasma gondii Growth in Vitro","volume":"4","author":"Radke","year":"2018","journal-title":"ACS Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Dos Santos, M., Oliveira Costa, A.L., De Souza Vaz, G.H., De Souza , G.C.A., De Almeida Vitor , R.W., and Martins-Duarte, \u00c9.S. (2023). Medicines for Malaria Venture Pandemic Box In Vitro Screening Identifies Compounds Highly Active against the Tachyzoite Stage of Toxoplasma gondii. Trop. Med. Infect. Dis., 8.","DOI":"10.3390\/tropicalmed8120510"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1017\/S0031182023000999","article-title":"Anti- Toxoplasma gondii Screening of MMV Pandemic Response Box and Evaluation of RWJ-67657 Efficacy in Chronically Infected Mice","volume":"150","author":"Ramos","year":"2023","journal-title":"Parasitology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/S0960-894X(01)81162-8","article-title":"5-(3-Carboxymethoxyphenyl)-2-(4,5-Dimethylthiazolyl)-3-(4-Sulfophenyl)Tetrazolium, Inner Salt (MTS) and Related Analogs of 3-(4,5-Dimethylthiazolyl)-2,5-Diphenyltetrazolium Bromide (MTT) Reducing to Purple Water-Soluble Formazans As Cell-Viability Indicators","volume":"1","author":"Barltrop","year":"1991","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Martins-Duarte, E.S., de Araujo Portes, J., de Araujo Portes, J., da Silva, R.B., Pires, H.S., Garden, S.J., and de Souza, W. (2021). In Vitro Activity of N-Phenyl-1,10-Phenanthroline-2-Amines against Tachyzoites and Bradyzoites of Toxoplasma gondii. Bioorganic Med. Chem., 50.","DOI":"10.1016\/j.bmc.2021.116467"},{"key":"ref_25","first-page":"17","article-title":"Effect of Carbohydrates, Periodate and Enzymes in the Process of Endocytosis of Trypanosoma Cruzi by Macrophages","volume":"41","year":"1984","journal-title":"Acta Trop."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Martins-Duarte, E.S., Dubar, F., Lawton, P., Fran\u00e7a Da Silva, C., Soeiro, M.D.N.C., De Souza, W., Biot, C., and Vommaro, R.C. (2015). Ciprofloxacin Derivatives Affect Parasite Cell Division and Increase the Survival of Mice Infected with Toxoplasma gondii. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0125705"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Cajazeiro, D.C., Toledo, P.P.M., De Sousa, N.F., Scotti, M.T., and Reim\u00e3o, J.Q. (2022). Drug Repurposing Based on Protozoan Proteome: In Vitro Evaluation of In Silico Screened Compounds against Toxoplasma gondii. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14081634"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1111\/j.1574-6968.2008.01130.x","article-title":"Itraconazole Affects Toxoplasma gondii Endodyogeny","volume":"282","author":"Vommaro","year":"2008","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.exppara.2009.12.011","article-title":"Toxoplasma gondii: Fluconazole and Itraconazole Activity against Toxoplasmosis in a Murine Model","volume":"124","author":"Lemgruber","year":"2010","journal-title":"Exp. Parasitol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1128\/AAC.34.5.775","article-title":"In Vitro and in Vivo Effects of Doxycycline on Toxoplasma gondii","volume":"34","author":"Chang","year":"1990","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1097\/00007890-198605000-00012","article-title":"The Effects of Vyclosporine on Toxoplasma gondii In Vivo and In Vitro","volume":"41","author":"McCabe","year":"1986","journal-title":"Transplantation"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e00042-15","DOI":"10.1128\/mSphere.00042-15","article-title":"Drug Repurposing Screening Identifies Novel Compounds That Effectively Inhibit Toxoplasma gondii Growth","volume":"1","author":"Dittmar","year":"2016","journal-title":"mSphere"},{"key":"ref_33","first-page":"369","article-title":"In Vitro Screening to Identify Anti-Toxoplasma Compounds and In Silico Modeling for Bioactivities and Toxicity","volume":"92","author":"Adeyemi","year":"2019","journal-title":"Yale J. Biol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Dos Santos, B.R., Ramos, A.B.D.S.B., De Menezes, R.P.B., Scotti, M.T., Colombo, F.A., Marques, M.J., and Reim\u00e3o, J.Q. (2023). Repurposing the Medicines for Malaria Venture\u2019s COVID Box to Discover Potent Inhibitors of Toxoplasma gondii, and In Vivo Efficacy Evaluation of Almitrine Bismesylate (MMV1804175) in Chronically Infected Mice. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0288335"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.ijpddr.2018.12.004","article-title":"New Life for an Old Drug: In Vitro and in Vivo Effects of the Anthelmintic Drug Niclosamide against Toxoplasma gondii RH Strain","volume":"9","author":"Zhang","year":"2019","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2388","DOI":"10.1073\/pnas.92.6.2388","article-title":"Selective Labeling of Intracellular Parasite Proteins by Using Ricin","volume":"92","author":"Gurnett","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"19","DOI":"10.5152\/balkanmedj.2012.098","article-title":"In Vitro Effects ofIvermectin and Sulphadiazine on Toxoplasma gondii","volume":"30","author":"Bilgin","year":"2013","journal-title":"Balk. Med. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2228","DOI":"10.1007\/s00044-021-02803-9","article-title":"Synthesis and Evaluation of Mycophenolic Acid Derivatives as Potential Anti-Toxoplasma gondii Agents","volume":"30","author":"Shang","year":"2021","journal-title":"Med. Chem. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1007\/s00436-017-5738-x","article-title":"Mycophenolic Acid Induces Differentiation of Toxoplasma gondii RH Strain Tachyzoites into Bradyzoites and Formation of Cyst-like Structure in Vitro","volume":"117","year":"2018","journal-title":"Parasitol. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1111\/j.1365-2958.2009.06655.x","article-title":"Disruption of a Mitochondrial MutS DNA Repair Enzyme Homologue Confers Drug Resistance in the Parasite Toxoplasma gondii","volume":"72","author":"Garrison","year":"2009","journal-title":"Mol. Microbiol."},{"key":"ref_41","first-page":"171","article-title":"Studies on Cycloheximide-Related Compounds. I Esters of Cycloheximide and Their Antitoxoplasmic Activity","volume":"18","author":"Egawa","year":"1965","journal-title":"J. Antibiot. Ser. A"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1172\/JCI117665","article-title":"Inhibition of Cytoplasmic and Organellar Protein Synthesis in Toxoplasma gondii. Implications for the Target of Macrolide Antibiotics","volume":"95","author":"Beckers","year":"1995","journal-title":"J. Clin. Investig."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1128\/AAC.39.7.1530","article-title":"In Vitro Assays Elucidate Peculiar Kinetics of Clindamycin Action against Toxoplasma gondii","volume":"39","author":"Fichera","year":"1995","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Daina, A., Michielin, O., and Zoete, V. (2017). SwissADME: A Free Web Tool to Evaluate Pharmacokinetics, Drug-Likeness and Medicinal Chemistry Friendliness of Small Molecules. Sci. Rep., 7.","DOI":"10.1038\/srep42717"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(96)00423-1","article-title":"Experimental and Computational Approaches to Estimate Solubility and Permeability in Drug Discovery and Development Settings","volume":"23","author":"Lipinski","year":"1997","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2615","DOI":"10.1021\/jm020017n","article-title":"Molecular Properties That Influence the Oral Bioavailability of Drug Candidates","volume":"45","author":"Veber","year":"2002","journal-title":"J. Med. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4066","DOI":"10.1021\/acs.jmedchem.5b00104","article-title":"pkCSM: Predicting Small-Molecule Pharmacokinetic and Toxicity Properties Using Graph-Based Signatures","volume":"58","author":"Pires","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_48","first-page":"391","article-title":"The Effect of Cytochrome P450 Metabolism on Drug Response, Interactions, and Adverse Effects","volume":"76","author":"Lynch","year":"2007","journal-title":"Am. Fam. Physician."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.2174\/13816128113199990463","article-title":"Transporters at CNS Barrier Sites: Obstacles or Opportunities for Drug Delivery?","volume":"20","author":"Slosky","year":"2014","journal-title":"Curr. Pharm. Des."},{"key":"ref_50","first-page":"124","article-title":"Anisomycin Is a Multifunctional Drug: More than Just a Tool to Inhibit Protein Synthesis","volume":"4","year":"2010","journal-title":"Curr. Chem. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"356","DOI":"10.3758\/BF03333842","article-title":"Can Commonly Used Antibiotics Disrupt Formation of New Memories?","volume":"22","author":"Osborn","year":"1984","journal-title":"Bull. Psychon. Soc."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"12856","DOI":"10.1038\/ncomms12856","article-title":"Structure\u2013Function Insights Reveal the Human Ribosome as a Cancer Target for Antibiotics","volume":"7","author":"Myasnikov","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/nchembio.304","article-title":"Inhibition of Eukaryotic Translation Elongation by Cycloheximide and Lactimidomycin","volume":"6","author":"Ju","year":"2010","journal-title":"Nat. Chem. Biol."},{"key":"ref_54","first-page":"151","article-title":"Regulation of mammalian protein synthesis In Vivo. Protein synthesis in rat liver and kidney after the administration of sublethal doses of cyclohyximide","volume":"178","author":"Duhl","year":"1976","journal-title":"Biochem. J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/nature13737","article-title":"Structural Basis for the Inhibition of the Eukaryotic Ribosome","volume":"513","author":"Prokhorova","year":"2014","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.plipres.2013.06.003","article-title":"Lipid Synthesis in Protozoan Parasites: A Comparison between Kinetoplastids and Apicomplexans","volume":"52","author":"Ramakrishnan","year":"2013","journal-title":"Prog. Lipid Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3320","DOI":"10.1242\/jcs.185223","article-title":"Apicoplast Fatty Acid Synthesis Is Essential for Pellicle Formation at the End of Cytokinesis in Toxoplasma gondii","volume":"129","author":"Carias","year":"2016","journal-title":"J. Cell Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.parint.2009.08.004","article-title":"Thiolactomycin Analogues as Potential Anti-Toxoplasma gondii Agents","volume":"58","author":"Jones","year":"2009","journal-title":"Parasitol. Int."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1046\/j.1365-2958.2002.02825.x","article-title":"An rRNA Mutation Identifies the Apicoplast as the Target for Clindamycin in Toxoplasma gondii","volume":"43","author":"Camps","year":"2002","journal-title":"Mol. Microbiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3226","DOI":"10.1016\/S0021-9258(18)95953-3","article-title":"Inhibitors of Protein Biosynthesis","volume":"242","author":"Grollman","year":"1967","journal-title":"J. Biol. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"8582","DOI":"10.1074\/jbc.M509043200","article-title":"Importance of the Different Proteolytic Sites of the Proteasome and the Efficacy of Inhibitors Varies with the Protein Substrate","volume":"281","author":"Kisselev","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1002\/psc.1107","article-title":"The Persisting Challenge of Selective and Specific Proteasome Inhibition","volume":"15","author":"Groll","year":"2009","journal-title":"J. Pept. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1186\/2193-1801-2-566","article-title":"Analysis of Bortezomib Inhibitor Docked within the Catalytic Subunits of the Plasmodium falciparum 20S Proteasome","volume":"2","author":"Sridhar","year":"2013","journal-title":"SpringerPlus"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1186\/1475-2875-7-187","article-title":"Comprehensive Study of Proteasome Inhibitors against Plasmodium falciparum Laboratory Strains and Field Isolates from Gabon","volume":"7","author":"Kreidenweiss","year":"2008","journal-title":"Malar. J."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1007\/s00277-011-1377-y","article-title":"The Proteasome Inhibitor Bortezomib Targets Cell Cycle and Apoptosis and Acts Synergistically in a Sequence-Dependent Way with Chemotherapeutic Agents in Mantle Cell Lymphoma","volume":"91","author":"Hutter","year":"2012","journal-title":"Ann. Hematol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"807","DOI":"10.2165\/0003088-200847120-00005","article-title":"A Mechanism-Based Population Pharmacokinetic Model for Characterizing Time-Dependent Pharmacokinetics of Midostaurin and Its Metabolites in Human Subjects","volume":"47","author":"Yin","year":"2008","journal-title":"Clin. Pharmacokinet."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1182\/blood-2005-07-3022","article-title":"PKC412 Inhibits In Vitro Growth of Neoplastic Human Mast Cells Expressing the D816V-Mutated Variant of KIT: Comparison with AMN107, Imatinib, and Cladribine (2CdA) and Evaluation of Cooperative Drug Effects","volume":"107","author":"Gleixner","year":"2006","journal-title":"Blood"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Mayol, G.F., Revuelta, M.V., Salusso, A., Touz, M.C., and R\u00f3polo, A.S. (2020). Evidence of Nuclear Transport Mechanisms in the Protozoan Parasite Giardia lamblia. Biochim. Biophys. Acta (BBA) Mol. Cell Res., 1867.","DOI":"10.1016\/j.bbamcr.2019.118566"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1007\/s11250-022-03228-1","article-title":"In Vitro Anti-Trypanosomal Effect of Ivermectin on Trypanosoma evansi by Targeting Multiple Metabolic Pathways","volume":"54","author":"Gupta","year":"2022","journal-title":"Trop. Anim. Health Prod."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Fraccaroli, L., Ruiz, M.D., Perdomo, V.G., Clausi, A.N., Balcazar, D.E., Larocca, L., and Carrillo, C. (2022). Broadening the Spectrum of Ivermectin: Its Effect on Trypanosoma cruzi and Related Trypanosomatids. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.885268"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"108059","DOI":"10.1016\/j.exppara.2020.108059","article-title":"Ivermectin Presents Effective and Selective Antileishmanial Activity In Vitro and in Vivo against Leishmania infantum and Is Therapeutic against Visceral Leishmaniasis","volume":"221","author":"Reis","year":"2021","journal-title":"Exp. Parasitol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e59384","DOI":"10.7554\/eLife.59384","article-title":"Toxoplasma TgATG9 Is Critical for Autophagy and Long-Term Persistence in Tissue Cysts","volume":"10","author":"Smith","year":"2021","journal-title":"eLife"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Liu, J., Liang, H., Chen, C., Wang, X., Qu, F., Wang, H., Yang, K., Wang, Q., Zhao, N., and Meng, J. (2019). Ivermectin Induces Autophagy-Mediated Cell Death through the AKT\/mTOR Signaling Pathway in Glioma Cells. Biosci. Rep., 39.","DOI":"10.1042\/BSR20192489"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S0162-3109(00)00193-4","article-title":"The Structure of Inosine 5\u2032-Monophosphate Dehydrogenase and the Design of Novel Inhibitors","volume":"47","author":"Sintchak","year":"2000","journal-title":"Immunopharmacology"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1111\/cmi.12426","article-title":"Toxoplasma gondii Vps11, a Subunit of HOPS and CORVET Tethering Complexes, Is Essential for the Biogenesis of Secretory Organelles","volume":"17","author":"Pastore","year":"2015","journal-title":"Cell Microbiol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Sakura, T., Sindikubwabo, F., Oesterlin, L.K., Bousquet, H., Slomianny, C., Hakimi, M.-A., Langsley, G., and Tomavo, S. (2016). A Critical Role for Toxoplasma gondii Vacuolar Protein Sorting VPS9 in Secretory Organelle Biogenesis and Host Infection. Sci. Rep., 6.","DOI":"10.1038\/srep38842"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"113601","DOI":"10.1016\/j.celrep.2023.113601","article-title":"Toxoplasma Membrane Inositol Phospholipid Binding Protein TgREMIND Is Essential for Secretory Organelle Function and Host Infection","volume":"43","author":"Houngue","year":"2024","journal-title":"Cell Rep."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"14010","DOI":"10.1074\/jbc.271.24.14010","article-title":"Insertional Tagging, Cloning, and Expression of the Hypoxanthine-Xanthine-Guanine Phosphoribosyltransferase Gene","volume":"271","author":"Donald","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"101214","DOI":"10.1016\/j.animal.2024.101214","article-title":"Safety and Transfer of Veterinary Drugs from Substrate to Black Soldier Fly Larvae","volume":"18","author":"Zoet","year":"2024","journal-title":"Animal"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1093\/ps\/78.12.1681","article-title":"The Effect of Flavophospholipol (Flavomycin) and Salinomycin Sodium (Sacox) on the Excretion of Clostridium perfringens, Salmonella enteritidis, and Campylobacter jejuni in Broilers after Experimental Infection","volume":"78","author":"Bolder","year":"1999","journal-title":"Poult. Sci."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/12\/12\/2602\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:53:10Z","timestamp":1760115190000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/12\/12\/2602"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,16]]},"references-count":80,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["microorganisms12122602"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms12122602","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,16]]}}}