國家衛生研究院 NHRI:Item 3990099045/12231
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    题名: Anti-inflammatory compound shows therapeutic safety and efficacy against flavivirus infection
    作者: Chuang, FK;Huang, SM;Liao, CL;Lee, AR;Lien, SP;Chiu, YL;Chang, TH;Tsai, PL;Lin, RJ;Shih, CC;Tsai, YJ;Lin, GJ;Yen, LC
    贡献者: National Institute of Infectious Diseases and Vaccinology;National Mosquito-Borne Diseases Control Research Center
    摘要: Flaviviruses comprise several medically important viruses, including Japanese encephalitis virus, West Nile virus, dengue virus (DENV), yellow fever virus and Zika virus (ZIKV). A large outbreak of DENV and ZIKV occurred recently, leading to many cases of illness and death. However, despite decades of efforts, we have no clinically specific therapeutic drugs against DENV and ZIKV. Previous studies showed that inflammatory responses play a critical role in dengue and Zika pathogenesis. Thus, in this study, we examined a series of novel anti-inflammatory compounds and found that treatment with compound 2d could dose-dependently reduce viral protein expression and viral progeny production in HEK-293 and Raw264.7 cells with four serotypes of DENV and ZIKV infection. As well, considering medication safety, compound 2d could not suppress cyclooxygenase-1 (COX-1) enzymatic activities and thus could prevent bleeding side effect. Moreover, compound 2d significantly inhibited COX-2 enzymatic activities and prostaglandin E2 levels, associated with viral replication, as compared with a selective COX-2 inhibitor, celecoxib. Furthermore, administering 5 mg/kg compound 2d to DENV-2-infected AG129 mice prolonged survival and reduced viremia and serum cytokine levels. Overall, compound 2d showed therapeutic safety and efficacy in vitro and in vivo and could be further developed as a potential therapeutic agent for flavivirus infection.
    日期: 2020-01
    關聯: Antimicrobial Agents and Chemotherapy. 2020 Jan;64(1):Article number e00941-19.
    Link to: http://dx.doi.org/10.1128/aac.00941-19
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0066-4804&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000503839600007
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85077016896
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