Anti-inflammatory Compound Shows Therapeutic Safety and Efficacy against Flavivirus Infection

Abstract

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 effort, 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 virus 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 infected with four serotypes of DENV and ZIKV. In addition, considering medication safety, compound 2d could not suppress cyclooxygenase-1 (COX-1) enzymatic activities and thus could prevent the side effect of bleeding. Moreover, compound 2d significantly inhibited COX-2 enzymatic activities and prostaglandin E2 levels, associated with viral replication, compared to results 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.

The anti-viral facet of anti-rheumatic drugs: Lessons from COVID-19

“…The COX-2 is an important mediator of inflammation in response to viral infection, and it contributes to viral replication, for CMV, HCV, and viruses belonging to the Flaviviridae family. Recently, it has been documented that compounds that significantly inhibit COX-2 enzymatic activities and prostaglandin E2 levels, associated with viral replication, showed therapeutic safety and efficacy in vitro and in vivo for Flaviviridae infection [58].…”

Drug screening identified that handelin inhibits feline calicivirus infection by inhibiting HSP70 expression in vitro

“…IFAs were conducted to observe FCV-infected CRFK cells, as described elsewhere with some modifications [29][30][31]. Briefly, cells were fixed with 4 % paraformaldehyde for 30 min and then permeabilized with 0.3 % Triton X-100 for 10 min at room temperature.…”

Encephalitic Arboviruses of Africa: Emergence, Clinical Presentation and Neuropathogenesis

“…While there are currently no treatments that limit the replication of specific arboviruses in the CNS, anti-inflammatory treatments, including corticosteroids, have been used in patients with chorioretintis, encephalitis or myelitis ( 86 – 88 ). New anti-inflammatory compounds are also under development ( 89 ).…”