AR-12 suppresses dengue virus replication by down-regulation of PI3K/AKT and GRP78

doi:10.1016/j.antiviral.2017.02.015

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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.
關聯:	Antiviral Research, v.142, pp.158-168
顯示於類別:	[化妝品應用與管理系(所)] 期刊論文

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