{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:00:07Z","timestamp":1790802007212,"version":"4.1.0"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2023,7,7]],"date-time":"2023-07-07T00:00:00Z","timestamp":1688688000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2018\/18954-4"],"award-info":[{"award-number":["2018\/18954-4"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2020\/03399-5"],"award-info":[{"award-number":["2020\/03399-5"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Toxoplasmosis, caused by the obligate intracellular parasite <jats:italic>Toxoplasma gondii<\/jats:italic>, affects about one-third of the world\u2019s population and can cause severe congenital, neurological and ocular issues. Current treatment options are limited, and there are no human vaccines available to prevent transmission. Drug repurposing has been effective in identifying anti-<jats:italic>T<\/jats:italic>. <jats:italic>gondii<\/jats:italic> drugs. In this study, the screening of the COVID Box, a compilation of 160 compounds provided by the \"Medicines for Malaria Venture\" organization, was conducted to explore its potential for repurposing drugs to combat toxoplasmosis. The objective of the present work was to evaluate the compounds\u2019 ability to inhibit <jats:italic>T<\/jats:italic>. <jats:italic>gondii<\/jats:italic> tachyzoite growth, assess their cytotoxicity against human cells, examine their absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, and investigate the potential of one candidate drug through an experimental chronic model of toxoplasmosis. Early screening identified 29 compounds that could inhibit <jats:italic>T<\/jats:italic>. <jats:italic>gondii<\/jats:italic> survival by over 80% while keeping human cell survival up to 50% at a concentration of 1 \u03bcM. The Half Effective Concentrations (EC<jats:sub>50<\/jats:sub>) of these compounds ranged from 0.04 to 0.92 \u03bcM, while the Half Cytotoxic Concentrations (CC<jats:sub>50<\/jats:sub>) ranged from 2.48 to over 50 \u03bcM. Almitrine was chosen for further evaluation due to its favorable characteristics, including anti-<jats:italic>T<\/jats:italic>. <jats:italic>gondii<\/jats:italic> activity at nanomolar concentrations, low cytotoxicity, and ADMET properties. Administering almitrine bismesylate (Vectarion\u00ae) orally at dose of 25 mg\/kg\/day for ten consecutive days resulted in a statistically significant (p &lt; 0.001) reduction in parasite burden in the brains of mice chronically infected with <jats:italic>T<\/jats:italic>. <jats:italic>gondii<\/jats:italic> (ME49 strain). This was determined by quantifying the RNA of living parasites using real-time PCR. The presented results suggest that almitrine may be a promising drug candidate for additional experimental studies on toxoplasmosis and provide further evidence of the potential of the MMV collections as a valuable source of drugs to be repositioned for infectious diseases.<\/jats:p>","DOI":"10.1371\/journal.pone.0288335","type":"journal-article","created":{"date-parts":[[2023,7,7]],"date-time":"2023-07-07T17:42:30Z","timestamp":1688751750000},"page":"e0288335","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["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"],"prefix":"10.1371","volume":"18","author":[{"given":"Bruna Ramos","family":"dos Santos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0406-1823","authenticated-orcid":true,"given":"Amanda Bruno da Silva Bellini","family":"Ramos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata Priscila Barros","family":"de Menezes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus Tullius","family":"Scotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e1bio Ant\u00f4nio","family":"Colombo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos Jos\u00e9","family":"Marques","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4418-0838","authenticated-orcid":true,"given":"Juliana Quero","family":"Reim\u00e3o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,7,7]]},"reference":[{"key":"pone.0288335.ref001","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1079\/AHR2005100","article-title":"Biology and epidemiology of Toxoplasma gondii in man and animals","volume":"6","author":"DE Hill","year":"2005","journal-title":"Anim Heal Res Rev"},{"key":"pone.0288335.ref002","doi-asserted-by":"crossref","first-page":"e90203","DOI":"10.1371\/journal.pone.0090203","article-title":"Toxoplasmosis\u2013A Global Threat. 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