THE ANTIVIRAL ACTIVITY OF PHENOLIC LIPIDS GROUP AGAINST DENGUE VIRUS

Abstract

Dengue virus causes a global burden that specific chemotherapy has not been established in a clinical setting. A previous report suggested that anacardic acid saturated (C15:0), a member of phenolic lipids, inhibited hepatitis C virus infection. Here, we explored structure activity relationship of phenolic lipids homologues with anti-DENV properties in the cell-based system. Our results indicated that Cardol triene (C15:3) expressed DENV1-4 inhibition, but not to Zika virus (SV0010/15) with the EC50s of 5.35 ± 1.16 µM, 7.13 ± 0.72 µM, 8.98 ± 1.77 µM, and 8.21 ± 0.34 µM, respectively. Also, the compound showed good CC50s to Vero cells and human-derived HepG-2, THP-1, and HEK-293 cell lines at 207.30 ± 5.24 µM, 140.27 ± 8.44 µM, 129.77 ± 12.08 µM, and 92.80 ± 3.93 µM, respectively. Time of drug addition assay revealed that the compound inhibited the virus at both early and late phases post-infection. We observed that the compound interfered intracellular RNA and infectious virion at 87.00 ± 6.43 percent and 91.73 ± 4.53 percent, respectively when introduced at post-attachment. Cardol triene inhibited only dengue fusion, but not Zika virus fusion, the mechanism of action was also investigated and results showed that the molecular targets were likely kl-loops of DENV envelope protein. Moreover, the compound inhibited BHK-21/DENV2 replicon replication with 76.60 ± 7.59 percent and 89.44 ± 4.02 percent at 10 µM and 20 µM, respectively. Therefore, the replication could be the target of cardol triene at late stage. This study showed for the first time that CNSL-derived phenolic lipid had a potential for further development as anti-dengue inhibitors.