{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T06:07:41Z","timestamp":1760854061362,"version":"3.37.3"},"reference-count":11,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,11,9]],"date-time":"2018-11-09T00:00:00Z","timestamp":1541721600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,11,9]],"date-time":"2018-11-09T00:00:00Z","timestamp":1541721600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST105-2320-B-039-053-MY3"],"award-info":[{"award-number":["MOST105-2320-B-039-053-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Japanese encephalitis virus (JEV) is a member of neurotropic flaviviruses transmitted by mosquito bites, causing severe central nervous system disorders. Current JEV genotype III vaccines have a low protection against genotype I isolates in the risk zone. The lead compound CW-33, ethyl 2-(3\u2032,5\u2032-dimethylanilino)-4-oxo-4,5-dihydrofuran-3-carboxylate, demonstrates the antiviral activity against JEV with an IC<jats:sub>50<\/jats:sub> values of 38.5\u2009\u03bcM for virus yield reduction (Int J Mol Sci 2016,17: E1386). This study synthesized fourteen CW-33 analogues containing a fluoro atom or one methoxy group at the C-2, C-3, or C-4 of anilino ring, and then evaluated for their antiviral activity and mechanism. Among 6 amalogues, CW-33A (ethyl 2-(2-fluoroanilino)-4-oxo- 4,5-dihydrofuran-3-carboxylate), and CW-33D (ethyl 2-(3-methoxyanilino)-4-oxo- 4,5-dihydrofuran-3-carboxylate exhibited antiviral potentials in viral cytopathic effect (CPE) inhibition. CW-33A significantly suppressed the viral protein expression, genome synthesis and intracellular JEV particle production, showing a higher inhibitory effect on JEV yield than CW-33 and CW-33D. The study demonstrated that a mono-fluoro substitution on at the C-2 anilino ring of CW-33 improved the antiviral activity JEV, revealing the structure-activity relationship for developing novel agents against JEV infection.<\/jats:p>","DOI":"10.1038\/s41598-018-34932-4","type":"journal-article","created":{"date-parts":[[2018,11,5]],"date-time":"2018-11-05T10:37:49Z","timestamp":1541414269000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Structure analysis and antiviral activity of CW-33 analogues against Japanese encephalitis virus"],"prefix":"10.1038","volume":"8","author":[{"given":"Jin-Cherng","family":"Lien","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ching-Ying","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsueh\u2013Chou","family":"Lai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chien-Yi","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Fong","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ging-Yan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0223-1577","authenticated-orcid":false,"given":"Kuan-Chung","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"An-Cheng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Su-Hua","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng-Wen","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,11,9]]},"reference":[{"key":"34932_CR1","doi-asserted-by":"publisher","first-page":"155","DOI":"10.2217\/fmb.12.139","volume":"8","author":"LL Coffey","year":"2013","unstructured":"Coffey, L. L., Forrester, N., Tsetsarkin, K., Vasilakis, N. & Weaver, S. C. Factors shaping the adaptive landscape for arboviruses: implications for the emergence of disease. Future. Microbiol. 8, 155\u2013176 (2013).","journal-title":"Future. Microbiol."},{"key":"34932_CR2","doi-asserted-by":"publisher","first-page":"4864","DOI":"10.1128\/JVI.00252-16","volume":"90","author":"HM Lazear","year":"2016","unstructured":"Lazear, H. M. & Diamond, M. S. Zika virus: new clinical syndromes and its emergence in the Western Hemisphere. J. Virol. 90, 4864\u20134875 (2016).","journal-title":"J. Virol."},{"key":"34932_CR3","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/j.antiviral.2009.10.008","volume":"85","author":"SC Weaver","year":"2010","unstructured":"Weaver, S. C. & Reisen, W. K. Present and future arboviral threats. Antiviral Res. 85, 328\u2013345 (2010).","journal-title":"Antiviral Res."},{"key":"34932_CR4","doi-asserted-by":"publisher","first-page":"e1834","DOI":"10.1371\/journal.pntd.0001834","volume":"6","author":"YC Fan","year":"2012","unstructured":"Fan, Y. C. et al. Partially neutralizing potency against emerging genotype I virus among children received formalin-inactivated Japanese encephalitis virus vaccine. PLoS Negl. Trop. Dis. 6, e1834 (2012).","journal-title":"PLoS Negl. Trop. Dis."},{"key":"34932_CR5","doi-asserted-by":"publisher","first-page":"e55165","DOI":"10.1371\/journal.pone.0055165","volume":"8","author":"HJ Seo","year":"2013","unstructured":"Seo, H. J. et al. Molecular detection and genotyping of Japanese encephalitis virus in mosquitoes during a 2010 outbreak in the Republic of Korea. PLoS One. 8, e55165 (2013).","journal-title":"PLoS One."},{"key":"34932_CR6","doi-asserted-by":"publisher","first-page":"2354","DOI":"10.3201\/eid1712.110914","volume":"17","author":"YY Chen","year":"2011","unstructured":"Chen, Y. Y. et al. Japanese encephalitis virus genotype replacement, Taiwan, 2009-2010. Emerg. Infect. Dis. 17, 2354\u20132356 (2011).","journal-title":"Emerg. Infect. Dis."},{"key":"34932_CR7","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1186\/1743-422X-7-127","volume":"7","author":"SM Yun","year":"2010","unstructured":"Yun, S. M. et al. Molecular epidemiology of Japanese encephalitis virus circulating in South Korea, 1983-2005. Virol. J. 7, 127 (2010).","journal-title":"Virol. J."},{"key":"34932_CR8","doi-asserted-by":"publisher","first-page":"e2153","DOI":"10.1371\/journal.pntd.0002153","volume":"7","author":"JF Lindahl","year":"2013","unstructured":"Lindahl, J. F. et al. Circulation of Japanese encephalitis virus in pigs and mosquito vectors within Can Tho city, Vietnam. PLoS Negl. Trop. Dis. 7, e2153 (2013).","journal-title":"PLoS Negl. Trop. Dis."},{"key":"34932_CR9","doi-asserted-by":"publisher","first-page":"E1386","DOI":"10.3390\/ijms17091386","volume":"17","author":"SH Huang","year":"2016","unstructured":"Huang, S. H. et al. Antiviral Activity of a Novel Compound CW-33 against Japanese Encephalitis Virus through Inhibiting Intracellular Calcium Overload. Int. J. Mol. Sci. 17, E1386 (2016).","journal-title":"Int. J. Mol. Sci."},{"key":"34932_CR10","doi-asserted-by":"publisher","first-page":"E76","DOI":"10.3390\/v9040076","volume":"9","author":"CY Lu","year":"2017","unstructured":"Lu, C. Y. et al. Single-Round Infectious Particle Antiviral Screening Assays for the Japanese Encephalitis Virus. Viruses. 9, E76 (2017).","journal-title":"Viruses."},{"key":"34932_CR11","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/0378-4274(88)90031-8","volume":"43","author":"ML Gargas","year":"1988","unstructured":"Gargas, M. L., Seybold, P. G. & Andersen, M. E. Modeling the tissue solubilities and metabolic rate constant (Vmax) of halogenated methanes, ethanes, and ethylenes. Toxicol. Lett. 43, 235\u2013256 (1988).","journal-title":"Toxicol. Lett."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-34932-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-34932-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-34932-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T11:25:45Z","timestamp":1671621945000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-34932-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,9]]},"references-count":11,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["34932"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-34932-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"type":"electronic","value":"2045-2322"}],"subject":[],"published":{"date-parts":[[2018,11,9]]},"assertion":[{"value":"25 April 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 October 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 November 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"J.-C.L., A.-C.H. and C.-W.L. have three patents on CW-33 analogues. C.-Y.W., H.-C.L., C.-Y.L., Y.-F.L., G.-Y.G., K.-C.C. and S.-H.H. declare no potential conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"16595"}}