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.