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

Hsin Chen, Chien Chin Chen, Yee Shin Lin, Po Chun Chang, Zi Yi Lu, Chiou Feng Lin, Chia Ling Chen, Chih Peng Chang

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)158-168
Number of pages11
JournalAntiviral Research
Volume142
DOIs
Publication statusPublished - Jun 1 2017

Fingerprint

Dengue Virus
Virus Replication
Phosphatidylinositol 3-Kinases
Down-Regulation
Virus Diseases
Antiviral Agents
Celecoxib
Dengue
Prostaglandin-Endoperoxide Synthases
Taiwan
Fever
Up-Regulation
Public Health
Cell Culture Techniques
Viruses

Keywords

  • Antivirus
  • AR-12
  • Dengue
  • GRP78
  • PI3K/AKT

ASJC Scopus subject areas

  • Pharmacology
  • Virology

Cite this

AR-12 suppresses dengue virus replication by down-regulation of PI3K/AKT and GRP78. / Chen, Hsin; Chen, Chien Chin; Lin, Yee Shin; Chang, Po Chun; Lu, Zi Yi; Lin, Chiou Feng; Chen, Chia Ling; Chang, Chih Peng.

In: Antiviral Research, Vol. 142, 01.06.2017, p. 158-168.

Research output: Contribution to journalArticle

Chen, Hsin ; Chen, Chien Chin ; Lin, Yee Shin ; Chang, Po Chun ; Lu, Zi Yi ; Lin, Chiou Feng ; Chen, Chia Ling ; Chang, Chih Peng. / AR-12 suppresses dengue virus replication by down-regulation of PI3K/AKT and GRP78. In: Antiviral Research. 2017 ; Vol. 142. pp. 158-168.
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