Dengue virus (DENV) infection is still a global health problem. The severity of DENV infection is related to the high viral load and cytokine storm caused by excessive inflammation. There is no specific antiviral used for DENV. Meanwhile, the use of anti-inflammatory drugs for DENV is limited to patients with severe clinical symptoms. Interestingly, favipiravir (FVP) and quinine sulfate (QS) have been reported as repurposing drugs that can inhibit DENV replication. However, their anti-inflammatory activity in DENV infection has not been studied yet. Thus, the current study aimed to evaluate both antiviral and inflammatory activities of FVP and QS in Vero and PBMC cells. The FVP and QS antiviral activities were analyzed through half-maximal inhibitory concentration (IC50) and half-maximal cytotoxicity concentration (CC50) values against DENV serotype-1 on Vero cells. The anti-inflammatory activities of FVP and QS were measured by the relative expression of TNF-α, IL-6, IL-10 cytokines, and the transcription factor NF-κB from DENV-1 infected peripheral blood mononuclear cells (PBMC) in vitro. The results showed that the IC50, CC50, and selectivity index (SI) for FVP were 2.72 μg/mL, 156.78 μg/mL, and 58, respectively. Meanwhile, the IC50, CC50, and SI of QS were 14.97 μg/mL, 85.2 μg/mL, and 5.69. Also, FVP and QS reduced the expression of IL-6 and IL-10 but induced the expression of TNF-α, and the transcription factor NF-κB in PBMC with the presence of antibody-dependent enhancement (ADE). Further, FVP has better DENV-1 antiviral activities compared to QS. However, in comparison with QS, FVP showed lower anti-inflammatory activities. Further studies are needed to explore the antiviral and anti-inflammatory mechanism of FVP and QS in the DENV-infected models.
Key words: Antiviral Dengue, Anti-inflammatory, Favipiravir, Quinine Sulfate
|
