{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:06:09Z","timestamp":1790006769852,"version":"4.0.1"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Duck Tembusu virus (DTMUV) causes egg-drop syndrome and neurological symptoms in ducks, resulting in significant economic losses. Currently, no specific antiviral drugs are available for DTMUV infection. Scorpion-derived peptides have emerged as promising lead compounds for antiviral drug development. In this study, we investigated the antiviral activity and mechanism of the scorpion peptide Eval418 against DTMUV infection\n                      <jats:italic>in vitro<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>DF-1 cells were infected with DTMUV at an MOI of 0.1 and treated with Eval418 (0\u201320\u202f\u03bcM), with Ribavirin as a positive control. Antiviral activity was assessed by Western blot, RT-qPCR, and immunofluorescence assays targeting the DTMUV NS3 protein. Cytotoxicity and hemolytic activity were evaluated in DF-1, DEF, chicken and duck red blood cells the influence of duck serum on Eval418 was examined. Time-of-addition, free virion, attachment, and entry\/fusion assays were performed, along with transmission electron microscopy and molecular docking\/MD simulations of the NS3-Eval418 complex.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Eval418 inhibited DTMUV replication in a concentration-dependent manner, achieving over 99% inhibition at 10\u202f\u03bcM, with no significant cytotoxicity or hemolytic activity up to 120\u202f\u03bcM in all tested cells. Mechanistic studies revealed that Eval418 acted primarily during the coaddition stage by directly inactivating free virions, blocking viral attachment, and inhibiting viral entry\/fusion. TEM confirmed that Eval418 directly disrupted the morphological integrity of DTMUV virions, causing structural collapse. MD simulations showed that Eval418 binds stably to the NS3 binding pocket. Eval418 also inhibited two genetically distinct DTMUV isolates, whereas prolonged incubation with duck serum progressively reduced its antiviral activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings establish Eval418 as a promising lead compound for the development of antiviral therapeutics against DTMUV infection as a model flavivirus. Its potential efficacy against other flaviviruses requires further investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fvets.2026.1944118","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:44:11Z","timestamp":1790005451000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The scorpion peptide Eval418 inhibits duck Tembusu virus replication by disrupting viral structure and early-stage infection"],"prefix":"10.3389","volume":"13","author":[{"given":"Yuting","family":"Cheng","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory of Veterinary Bio-Pharmaceutical High Technology Research, Engineering Technology Research Center for Modern Animal Science and Novel Veterinary Pharmaceutic Development, Jiangsu Agri-Animal Husbandry Vocational College","place":["Taizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Feng","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Veterinary Bio-Pharmaceutical High Technology Research, Engineering Technology Research Center for Modern Animal Science and Novel Veterinary Pharmaceutic Development, Jiangsu Agri-Animal Husbandry Vocational College","place":["Taizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institutional Center for Shared Technologies and Facilities of Wuhan Institute of Virology, Chinese Academy of Sciences","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"Ma","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Veterinary Bio-Pharmaceutical High Technology Research, Engineering Technology Research Center for Modern Animal Science and Novel Veterinary Pharmaceutic Development, Jiangsu Agri-Animal Husbandry Vocational College","place":["Taizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Xie","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Veterinary Bio-Pharmaceutical High Technology Research, Engineering Technology Research Center for Modern Animal Science and Novel Veterinary Pharmaceutic Development, Jiangsu Agri-Animal Husbandry Vocational College","place":["Taizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anping","family":"Wang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Veterinary Bio-Pharmaceutical High Technology Research, Engineering Technology Research Center for Modern Animal Science and Novel Veterinary Pharmaceutic Development, Jiangsu Agri-Animal Husbandry Vocational College","place":["Taizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Wu","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Veterinary Bio-Pharmaceutical High Technology Research, Engineering Technology Research Center for Modern Animal Science and Novel Veterinary Pharmaceutic Development, Jiangsu Agri-Animal Husbandry Vocational College","place":["Taizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenfeng","family":"Jia","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Veterinary Bio-Pharmaceutical High Technology Research, Engineering Technology Research Center for Modern Animal Science and Novel Veterinary Pharmaceutic Development, Jiangsu Agri-Animal Husbandry Vocational College","place":["Taizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingguo","family":"Wu","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Veterinary Bio-Pharmaceutical High Technology Research, Engineering Technology Research Center for Modern Animal Science and Novel Veterinary Pharmaceutic Development, Jiangsu Agri-Animal Husbandry Vocational College","place":["Taizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixia","family":"Miao","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Basic Medical Sciences, Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanyuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Veterinary Bio-Pharmaceutical High Technology Research, Engineering Technology Research Center for Modern Animal Science and Novel Veterinary Pharmaceutic Development, Jiangsu Agri-Animal Husbandry Vocational College","place":["Taizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2413","DOI":"10.1099\/jgv.0.000908","article-title":"An updated review of avian-origin tembusu virus: a newly emerging avian flavivirus","volume":"98","author":"Zhang","year":"2017","journal-title":"J Gen Virol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"e811","DOI":"10.3390\/v16050811","article-title":"Advancements in research on duck tembusu virus infections","volume":"16","author":"Cheng","year":"2024","journal-title":"Viruses"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"2400","DOI":"10.1080\/21505594.2021.1974329","article-title":"Glycosylation on envelope glycoprotein of duck tembusu virus affects virus replication in vitro and contributes to the neurovirulence and pathogenicity in 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