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A machine-learning model trained on anti-Ebola virus (EBOV) screening data previously identified tilorone as a potent\n            <jats:italic>in vitro<\/jats:italic>\n            EBOV inhibitor, making it a candidate for the treatment of Ebola virus disease (EVD). In the present study, a series of\n            <jats:italic>in vitro<\/jats:italic>\n            ADMET (absorption, distribution, metabolism, excretion, toxicity) assays demonstrated the drug has excellent solubility, high Caco-2 permeability, was not a P-glycoprotein substrate, and had no inhibitory activity against five human CYP450 enzymes (3A4, 2D6, 2C19, 2C9, and 1A2). Tilorone was shown to have 52% human plasma protein binding with excellent plasma stability and a mouse liver microsome half-life of 48 min. Dose range-finding studies in mice demonstrated a maximum tolerated single dose of 100 mg\/kg of body weight. A pharmacokinetics study in mice at 2- and 10-mg\/kg dose levels showed that the drug is rapidly absorbed, has dose-dependent increases in maximum concentration of unbound drug in plasma and areas under the concentration-time curve, and has a half-life of approximately 18 h in both males and females, although the exposure was \u223c2.5-fold higher in male mice. Tilorone doses of 25 and 50 mg\/kg proved efficacious in protecting 90% of mice from a lethal challenge with mouse-adapted with once-daily intraperitoneal (i.p.) dosing for 8 days. A subsequent study showed that 30 mg\/kg\/day of tilorone given i.p. starting 2 or 24 h postchallenge and continuing through day 7 postinfection was fully protective, indicating promising activity for the treatment of EVD.\n          <\/jats:p>","DOI":"10.1128\/aac.01711-17","type":"journal-article","created":{"date-parts":[[2017,11,13]],"date-time":"2017-11-13T16:56:19Z","timestamp":1510592179000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":61,"title":["Efficacy of Tilorone Dihydrochloride against Ebola Virus Infection"],"prefix":"10.1128","volume":"62","author":[{"given":"Sean","family":"Ekins","sequence":"first","affiliation":[{"name":"Collaborations Pharmaceuticals, Inc., Raleigh, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary A.","family":"Lingerfelt","sequence":"additional","affiliation":[{"name":"Collaborations Pharmaceuticals, Inc., Raleigh, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason E.","family":"Comer","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"Institutional Office of Regulated Nonclinical Studies, University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander N.","family":"Freiberg","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon C.","family":"Mirsalis","sequence":"additional","affiliation":[{"name":"Bioscience Division, SRI International, Menlo Park, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"O'Loughlin","sequence":"additional","affiliation":[{"name":"Bioscience Division, SRI International, Menlo Park, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anush","family":"Harutyunyan","sequence":"additional","affiliation":[{"name":"Bioscience Division, SRI International, Menlo Park, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"McFarlane","sequence":"additional","affiliation":[{"name":"Bioscience Division, SRI International, Menlo Park, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol E.","family":"Green","sequence":"additional","affiliation":[{"name":"Bioscience Division, SRI International, Menlo Park, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter B.","family":"Madrid","sequence":"additional","affiliation":[{"name":"Bioscience Division, SRI International, Menlo Park, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1159\/000149300"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2017.02.006"},{"key":"e_1_3_2_4_2","first-page":"4","article-title":"FDA approved drugs as potential Ebola treatments","volume":"48","author":"Ekins S","year":"2015","unstructured":"Ekins S, Coffee M. 2015. 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