國家衛生研究院 NHRI:Item 3990099045/12747
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    題名: Antiviral activity of compound L3 against dengue and Zika viruses in vitro and in vivo
    作者: Chuang, FK;Liao, CL;Hu, MK;Chiu, YL;Lee, AR;Huang, SM;Chiu, YL;Tsai, PL;Su, BC;Chang, TH;Lin, CC;Shih, CC;Yen, LC
    貢獻者: National Institute of Infectious Diseases and Vaccinology
    摘要: 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.
    日期: 2020-06-05
    關聯: International Journal of Molecular Sciences. 2020 Jun 5;21(11):Article number 4050.
    Link to: http://dx.doi.org/10.3390/ijms21114050
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1422-0067&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000543400300312
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85086036291
    顯示於類別:[廖經倫] 期刊論文

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