{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T02:08:11Z","timestamp":1788055691761,"version":"build-2784847793"},"reference-count":45,"publisher":"National Academy of Sciences","issue":"8","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,2,23]]},"abstract":"<jats:p>\n                    Onchocerciasis, or river blindness, is a neglected tropical disease caused by the filarial nematode\n                    <jats:italic>Onchocerca volvulus<\/jats:italic>\n                    that affects more than 37\u00a0million people, mainly in third world countries. Currently, the only approved drug available for mass treatment is ivermectin, however, drug resistance is beginning to emerge, thus, new therapeutic targets and agents are desperately needed to treat and cure this devastating disease. Chitin metabolism plays a central role in invertebrate biology due to the critical structural function of chitin for the organism. Taken together with its absence in mammals, targeting chitin is an appealing therapeutic avenue. Importantly, the chitinase OvCHT1 from\n                    <jats:italic>O. volvulus<\/jats:italic>\n                    was recently discovered, however, its exact role in the worm\u2019s metabolism remains unknown. A screening effort against OvCHT1 was conducted using the Johns Hopkins Clinical Compound Library that contains over 1,500 existing drugs. Closantel, a veterinary anthelmintic with known proton ionophore activities, was identified as a potent and specific inhibitor of filarial chitinases, an activity not previously reported for this compound. Notably, closantel was found also to completely inhibit molting of\n                    <jats:italic>O. volvulus<\/jats:italic>\n                    infective L3 stage larvae. Closantel appears to target two important biochemical processes essential to filarial parasites. To begin to unravel closantel\u2019s effects, a retro-fragment-based study was used to define structural elements critical for closantel\u2019s chitinase inhibitor function. As resources towards the development of new agents that target neglected tropical diseases are scant, the finding of an existing drug with impact against\n                    <jats:italic>O. volvulus<\/jats:italic>\n                    provides promise in the hunt for new therapies against river blindness.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0915125107","type":"journal-article","created":{"date-parts":[[2010,2,8]],"date-time":"2010-02-08T21:53:28Z","timestamp":1265666008000},"page":"3424-3429","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":90,"title":["Repositioning of an existing drug for the neglected tropical disease Onchocerciasis"],"prefix":"10.1073","volume":"107","author":[{"given":"Christian","family":"Gloeckner","sequence":"first","affiliation":[{"name":"Departments of Chemistry and Immunology,"},{"name":"The Skaggs Institute for Chemical Biology, and"},{"name":"The Worm Institute for Research and Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda L.","family":"Garner","sequence":"additional","affiliation":[{"name":"Departments of Chemistry and Immunology,"},{"name":"The Skaggs Institute for Chemical Biology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fana","family":"Mersha","sequence":"additional","affiliation":[{"name":"New England Biolabs, 240 County Road, Ipswich, MA 01938-2723;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yelena","family":"Oksov","sequence":"additional","affiliation":[{"name":"Lindsley F. 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