{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:02:34Z","timestamp":1787022154159,"version":"build-2736575974"},"reference-count":80,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T00:00:00Z","timestamp":1734048000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI130186"],"award-info":[{"award-number":["R01AI130186"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    <jats:italic>Clostridioides difficile<\/jats:italic>\n                    is a major cause of nosocomial infections, often associated with individuals who have gut dysbiosis from previous antibiotic therapies.\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>difficile<\/jats:italic>\n                    infections (CDI) have a high recurrence rate and impose significant financial and mortality burdens on the healthcare system. Therefore, novel anti-\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>difficile<\/jats:italic>\n                    drugs are urgently needed to treat and reduce the severity and recurrence of infection. In this study, we screened a library of 618 antiviral drugs to identify a potential candidate for repurposing as novel anti-\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>difficile<\/jats:italic>\n                    therapeutics. Following our preliminary screening, we identified 9 novel compounds that inhibited\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>difficile<\/jats:italic>\n                    at a concentration of 16 \u03bcM or lower. Among these, 4 antiviral compounds demonstrated the most potent anti-\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>difficile<\/jats:italic>\n                    activity against a panel of 15\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>difficile<\/jats:italic>\n                    isolates, with minimum inhibitory concentrations (MICs) comparable to the drug of choice, vancomycin. These include rottlerin (MIC\n                    <jats:sub>50<\/jats:sub>\n                    = 0.25 \u03bcg\/mL), \u03b1-mangostin (MIC\n                    <jats:sub>50<\/jats:sub>\n                    = 1 \u03bcg\/mL), dryocrassin ABBA (MIC\n                    <jats:sub>50<\/jats:sub>\n                    = 1 \u03bcg\/mL), and obefazimod (MIC\n                    <jats:sub>50<\/jats:sub>\n                    = 4 \u03bcg\/mL). All exhibited minimal to no activity against representative members of the human gut microbiota. Interestingly, \u03b1-mangostin, a natural xanthone derived from the mangosteen fruit, exhibited strong bactericidal action, clearing a high inoculum of\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>difficile<\/jats:italic>\n                    in less than an hour. All other drugs exhibited bacteriostatic activity. Given their characteristics, these compounds show great promise as novel treatments for CDI.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0309624","type":"journal-article","created":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T13:34:22Z","timestamp":1734096862000},"page":"e0309624","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Screening novel antiviral compounds to treat Clostridioides difficile infections"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7305-1392","authenticated-orcid":true,"given":"Brice J.","family":"Stolz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9937-742X","authenticated-orcid":true,"given":"Ahmed A.","family":"Abouelkhair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0939-0458","authenticated-orcid":true,"given":"Mohamed N.","family":"Seleem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,12,13]]},"reference":[{"key":"pone.0309624.ref001","unstructured":"Prevention CfDCa. 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