{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T20:15:32Z","timestamp":1779912932747,"version":"3.53.1"},"reference-count":44,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2016,8,24]],"date-time":"2016-08-24T00:00:00Z","timestamp":1471996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, has five genotypes (I, II, III, IV, and V). JEV genotype I circulates widely in some Asian countries. However, current JEV vaccines based on genotype III strains show low neutralizing capacities against genotype I variants. In addition, JE has no specific treatment, except a few supportive treatments. Compound CW-33, an intermediate synthesized derivative of furoquinolines, was investigated for its antiviral activities against JEV in this study. CW-33 exhibited the less cytotoxicity to Syrian baby hamster kidney (BHK-21) and human medulloblastoma (TE761) cells. CW-33 dose-dependently reduced the cytopathic effect and apoptosis of JEV-infected cells. Supernatant virus yield assay pinpointed CW-33 as having potential anti-JEV activity with IC50 values ranging from 12.7 to 38.5 \u03bcM. Time-of-addition assay with CW-33 indicated that simultaneous and post-treatment had no plaque reduction activity, but continuous and simultaneous treatments proved to have highly effective antiviral activity, with IC50 values of 32.7 and 48.5 \u03bcM, respectively. CW-33 significantly moderated JEV-triggered Ca2+ overload, which correlated with the recovery of mitochondria membrane potential as well as the activation of Akt\/mTOR and Jak\/STAT1 signals in treated infected cells. Phosphopeptide profiling by LC-MS\/MS revealed that CW-33 upregulated proteins from the enzyme modulator category, such as protein phosphatase inhibitor 2 (I-2), Rho GTPase-activating protein 35, ARF GTPase-activating protein GIT2, and putative 3-phosphoinositide-dependent protein kinase 2. These enzyme modulators identified were associated with the activation of Akt\/mTOR and Jak\/STAT1 signals. Meanwhile, I-2 treatment substantially inhibited the apoptosis of JEV-infected cells. The results demonstrated that CW-33 exhibited a significant potential in the development of anti-JEV agents.<\/jats:p>","DOI":"10.3390\/ijms17091386","type":"journal-article","created":{"date-parts":[[2016,8,24]],"date-time":"2016-08-24T09:59:47Z","timestamp":1472032787000},"page":"1386","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Antiviral Activity of a Novel Compound CW-33 against Japanese Encephalitis Virus through Inhibiting Intracellular Calcium Overload"],"prefix":"10.3390","volume":"17","author":[{"given":"Su-Hua","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Asia University, Wufeng, Taichung 413, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Cherng","family":"Lien","sequence":"additional","affiliation":[{"name":"School of Pharmacy, China Medical University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-Jung","family":"Chen","sequence":"additional","affiliation":[{"name":"Proteomics Core Laboratory, Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Ching","family":"Liu","sequence":"additional","affiliation":[{"name":"Proteomics Core Laboratory, Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Fong","family":"Ping","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Fong","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An-Cheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Nursing, St. Mary\u2019s Junior College of Medicine, Nursing and Management, Yilan County 266, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Wen","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Asia University, Wufeng, Taichung 413, Taiwan"},{"name":"Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"155","DOI":"10.2217\/fmb.12.139","article-title":"Factors shaping the adaptive landscape for arboviruses: Implications for the emergence of disease","volume":"8","author":"Coffey","year":"2013","journal-title":"Future Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4864","DOI":"10.1128\/JVI.00252-16","article-title":"Zika virus: New clinical syndromes and its emergence in the Western Hemisphere","volume":"90","author":"Lazear","year":"2016","journal-title":"J. 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