{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:35:52Z","timestamp":1785418552835,"version":"3.56.0"},"reference-count":26,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Guangdong Basic and Applied Basic Research Foundation","doi-asserted-by":"publisher","award":["2023A1515011964"],"award-info":[{"award-number":["2023A1515011964"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Double First-Class Discipline Promotion Project","award":["2023B10564003"],"award-info":[{"award-number":["2023B10564003"]}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFD1801000"],"award-info":[{"award-number":["2023YFD1801000"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Guangdong Basic and Applied Basic Research Foundation","doi-asserted-by":"publisher","award":["2024A1515011658"],"award-info":[{"award-number":["2024A1515011658"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32473055"],"award-info":[{"award-number":["32473055"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100018925","name":"111 Center","doi-asserted-by":"crossref","award":["D20008"],"award-info":[{"award-number":["D20008"]}],"id":[{"id":"10.13039\/501100018925","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,5,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Fatty acid and retinol binding proteins (FARs) are nematode-specific proteins that orchestrate lipid metabolism, development, and host immune response. Here, the antagonists of\n                      <jats:italic toggle=\"yes\">Nippostrongylus brasiliensis<\/jats:italic>\n                      FAR-1 (\n                      <jats:italic toggle=\"yes\">Nb<\/jats:italic>\n                      FAR-1) were identified through integrating virtual screening, fluorescent ligand binding assay, and\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      egg hatching assays. An\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      mouse model was employed to evaluate anthelmintic efficacy against intestine-parasitized\n                      <jats:italic toggle=\"yes\">N. brasiliensis<\/jats:italic>\n                      and brain-parasitized\n                      <jats:italic toggle=\"yes\">Angiostrongylus cantonensis<\/jats:italic>\n                      . Forty-eight candidates were selected by virtual screening, six of them showed more than 40% antagonism to\n                      <jats:italic toggle=\"yes\">Nb<\/jats:italic>\n                      FAR-1 by fluorescent ligand-competition binding assay and suppressed\n                      <jats:italic toggle=\"yes\">N. brasiliensis<\/jats:italic>\n                      egg hatching by 40%\u201380% at 20 \u03bcM. In mice, E002-0872 and 4340-0245 reduced intestinal\n                      <jats:italic toggle=\"yes\">N. brasiliensis<\/jats:italic>\n                      burdens by 61.74% and 62.15%, respectively, and ameliorated intestinal damages. 4340-0245 reduced cerebral\n                      <jats:italic toggle=\"yes\">A. cantonensis<\/jats:italic>\n                      burdens by 52.73% and alleviated meningeal bleeding and neurological signs. Moreover, treatment with 4340-0245 at 15 mg\/kg shortened the body length of female worms, consistent with the higher\n                      <jats:italic toggle=\"yes\">far-1<\/jats:italic>\n                      expression in females. Alanine scanning showed I95 of\n                      <jats:italic toggle=\"yes\">Nb<\/jats:italic>\n                      FAR-1 as a key residue for binding fatty acid, retinol, and 4340-0245. Intraperitoneal administration of 4340-0245 at 50 mg\/kg did not cause any significant toxic effects, whereas 15 mg\/kg resulted in a plasma\n                      <jats:italic toggle=\"yes\">C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      of 56,473 ng\/mL at 10 min and a half-life of ~7 h. These data provide evidence that FAR-1 is a promising target for developing anthelmintic drugs.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01226-25","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T14:53:46Z","timestamp":1776264826000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Structure-guided screening of FAR-1 antagonists with multi-stage anthelmintic activity"],"prefix":"10.1128","volume":"70","author":[{"given":"Juan","family":"Wen","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05v9jqt67","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural University","place":["Guangzhou, 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