{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:32:31Z","timestamp":1791415951295,"version":"4.3.3"},"reference-count":36,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,6,5]],"date-time":"2020-06-05T00:00:00Z","timestamp":1591315200000},"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":["MOST 105-2628-B-016-002-MY2"],"award-info":[{"award-number":["MOST 105-2628-B-016-002-MY2"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of National Defense Medical Affairs Bureau","award":["MAB-107-078, MAB-108-054 and MAB-109-060"],"award-info":[{"award-number":["MAB-107-078, MAB-108-054 and MAB-109-060"]}]},{"DOI":"10.13039\/501100010425","name":"Tri-Service General Hospital","doi-asserted-by":"publisher","award":["TSGH-PH-106-02 and TSGH-PH-107-01"],"award-info":[{"award-number":["TSGH-PH-106-02 and TSGH-PH-107-01"]}],"id":[{"id":"10.13039\/501100010425","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dengue virus (DENV) and Zika virus (ZIKV) are mosquito-borne flaviviruses that cause severe illness after infection. Currently, there are no specific or effective treatments against DENV and ZIKV. Previous studies have shown that tyrosine kinase activities and signal transduction are involved in flavivirus replication, suggesting a potential therapeutic strategy for DENV and ZIKV. In this study, we found that compound L3 can significantly reduce viral protein expression and viral titers in HEK-293, MCF-7, HepG2, and Huh-7 cells and exhibits superior therapeutic efficacy against flaviviral infection compared to other tyrosine kinase inhibitors. In addition, compound L3 can decrease endogenous HER2 activation and inhibit the phosphorylation of the HER2 downstream signaling molecules Src and ERK1\/2, the levels of which have been associated with viral protein expression in MCF-7 cells. Moreover, silencing HER2 diminished DENV-2 and ZIKV expression in MCF-7 cells, which suggests that HER2 activity is involved in flavivirus replication. Furthermore, in DENV-2-infected AG129 mice, treatment with compound L3 increased the survival rates and reduced the viremia levels. Overall, compound L3 demonstrates therapeutic efficacy both in vitro and in vivo and could be developed as a promising antiviral drug against emerging flaviviruses or for concurrent DENV and ZIKV outbreaks.<\/jats:p>","DOI":"10.3390\/ijms21114050","type":"journal-article","created":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T05:16:14Z","timestamp":1591679774000},"page":"4050","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Antiviral Activity of Compound L3 against Dengue and Zika Viruses In Vitro and In Vivo"],"prefix":"10.3390","volume":"21","author":[{"given":"Fu-Kai","family":"Chuang","sequence":"first","affiliation":[{"name":"Penghu Branch of Tri-Service General Hospital, Penghu 88056, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Len","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, National Defense Medical Center, 161, Sec. 6, Min-Chuan E. Road, Neihu, Taipei 11490, Taiwan"},{"name":"National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 35053, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Kuan","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1827-6924","authenticated-orcid":false,"given":"Yi-Lin","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An-Rong","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Pharmacy, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Ming","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Lung","family":"Chiu","sequence":"additional","affiliation":[{"name":"School of Public Health, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Ling","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, National Defense Medical Center, 161, Sec. 6, Min-Chuan E. Road, Neihu, Taipei 11490, Taiwan"},{"name":"National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 35053, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo-Cyuan","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, National Defense Medical Center, 161, Sec. 6, Min-Chuan E. Road, Neihu, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4806-7864","authenticated-orcid":false,"given":"Tsung-Hsien","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, National Defense Medical Center, 161, Sec. 6, Min-Chuan E. Road, Neihu, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Chi","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, National Defense Medical Center, 161, Sec. 6, Min-Chuan E. Road, Neihu, Taipei 11490, Taiwan"},{"name":"Institute of Preventive Medicine, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Chin","family":"Shih","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1891-5546","authenticated-orcid":false,"given":"Li-Chen","family":"Yen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, National Defense Medical Center, 161, Sec. 6, Min-Chuan E. 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