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    Please use this identifier to cite or link to this item: http://ir.cnu.edu.tw/handle/310902800/31593


    標題: AR-12 suppresses dengue virus replication by down-regulation of PI3K/AKT and GRP78
    作者: Chen, Hsin-Hsin
    Chen, Chien-Chin
    Lin, Yee-Shin
    Chang, Po-Chun
    Lu, Zi-Yi
    Lin, Chiou-Feng
    Chen, Chia-Ling
    Chang, Chih-Peng
    貢獻者: Natl Cheng Kung Univ, Coll Med, Dept Microbiol & Immunol
    Chia Yi Christian Hosp, Dept Pathol
    Chia Nan Univ Pharm & Sci, Dept Cosmet Sci
    Natl Cheng Kung Univ, Inst Basic Med Sci, Coll Med
    Natl Cheng Kung Univ, Ctr Infect Dis & Signaling Res
    Taipei Med Univ, Grad Inst Med Sci, Coll Med
    Taipei Med Univ, Sch Med, Dept Microbiol & Immunol, Coll Med
    Taipei Med Univ, Translat Res Ctr
    關鍵字: AR-12
    Dengue
    PI3K/AKT
    GRP78
    Antivirus
    日期: 2017-06
    上傳時間: 2018-11-30 15:49:30 (UTC+8)
    出版者: Elsevier Science Bv
    摘要: Dengue virus (DENV) infection has become a public health issue of worldwide concern and is a serious health problem in Taiwan, yet there are no approved effective antiviral drugs to treat DENV. The replication of DENV requires both viral and cellular factors. Targeting host factors may provide a potential antiviral strategy. It has been known that up-regulation of PI3K/AKT signaling and GRP78 by DENV infection supports its replication. AR-12, a celecoxib derivative with no inhibiting activity on cyclooxygenase, shows potent inhibitory activities on both PI3K/AKT signaling and GRP78 expression levels, and recently has been found to block the replication of several hemorrhagic fever viruses. However the efficacy of AR-12 in treating DENV infection is still unclear. Here, we provide evidence to show that AR-12 is able to suppress DENV replication before or after virus infection in cell culture and mice. The antiviral activities of AR-12 are positive against infection of the four different DENV serotypes. AR-12 significantly down-regulates the PI3K/AKT activity and GRP78 expression in DENV infected cells whereas AKT and GRP78 rescue are able to attenuate anti-DENV effect of AR-12. Using a DENV-infected suckling mice model, we further demonstrate that treatment of AR-12 before or after DENV infection reduces virus replication and mice mortality. In conclusion, we uncover the potential efficacy of AR-12 as a novel drug for treating dengue. (C) 2017 Elsevier B.V. All rights reserved.
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