{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T16:02:15Z","timestamp":1760889735132,"version":"build-2065373602"},"reference-count":62,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2018,11,13]],"date-time":"2018-11-13T00:00:00Z","timestamp":1542067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2015R1C1A2A01051484"],"award-info":[{"award-number":["NRF-2015R1C1A2A01051484"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lymphatic filariasis and onchocerciasis caused by filarial nematodes are important diseases leading to considerable morbidity throughout tropical countries. Diethylcarbamazine (DEC), albendazole (ALB), and ivermectin (IVM) used in massive drug administration are not highly effective in killing the long-lived adult worms, and there is demand for the development of novel macrofilaricidal drugs affecting new molecular targets. A Ca2+ binding protein, calumenin, was identified as a novel and nematode-specific drug target for filariasis, due to its involvement in fertility and cuticle development in nematodes. As sterilizing and killing effects of the adult worms are considered to be ideal profiles of new drugs, calumenin could be an eligible drug target. Indeed, the Caenorhabditis elegans mutant model of calumenin exhibited enhanced drug acceptability to both microfilaricidal drugs (ALB and IVM) even at the adult stage, proving the roles of the nematode cuticle in efficient drug entry. Molecular modeling revealed that structural features of calumenin were only conserved among nematodes (C. elegans, Brugia malayi, and Onchocerca volvulus). Structural conservation and the specificity of nematode calumenins enabled the development of drugs with good target selectivity between parasites and human hosts. Structure-based virtual screening resulted in the discovery of itraconazole (ITC), an inhibitor of sterol biosynthesis, as a nematode calumenin-targeting ligand. The inhibitory potential of ITC was tested using a nematode mutant model of calumenin.<\/jats:p>","DOI":"10.3390\/ijms19113579","type":"journal-article","created":{"date-parts":[[2018,11,14]],"date-time":"2018-11-14T02:42:41Z","timestamp":1542163361000},"page":"3579","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Novel Findings of Anti-Filarial Drug Target and Structure-Based Virtual Screening for Drug Discovery"],"prefix":"10.3390","volume":"19","author":[{"given":"Tae-Woo","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Life Science, Hanyang University, Seoul 04763, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeong Hoon","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Biology Education, College of Education, Chosun University, Gwangju 61452, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joohong","family":"Ahnn","sequence":"additional","affiliation":[{"name":"Department of Life Science, Hanyang University, Seoul 04763, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7953-3384","authenticated-orcid":false,"given":"Hyun-Ok","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Infection Biology, Wonkwang University School of Medicine, Iksan 54538, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,11,13]]},"reference":[{"key":"ref_1","first-page":"288","article-title":"Determinants of parasite drug resistance in human lymphatic filariasis","volume":"29","author":"Cobo","year":"2016","journal-title":"Rev. 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