Berberine inhibitory action against zika and dengue viruses in cell cultures

Berberine (BBR) is a plant derived isoquinoline alkaloid that displays a great variety of biological activities. In this study we showed that BBR exhibits a strong antiviral activity with broad spectrum of inhibition against different strains of Zika virus (ZIKV) and the four serotypes of dengue virus (DENV) in Vero cells. The inhibitory effect of BBR on ZIKV and DENV-2 growth was also demonstrated in human cell lines. The analysis of BBR mode of action showed that the compound did not affect early events of viral multiplication cycle or viral protein expression. By contrast, BBR strongly impaired the formation of intracellular and extracellular infectious viral particles. Furthermore, BBR was able to inhibit ZIKV induced activation of ERK1/2 and p38 cell signaling pathways and also reduced p38 phosphorylation in uninfected cells. Like BBR, the p38 inhibitor SB202190 reduced p38 phosphorylation in both uninfected and ZIKV infected cultures and caused a significant diminishment of viral yields even when it was added late during the infection. These results suggest for the first time that the inhibitory effect of BBR on p38 signaling might contribute to the antiviral action of the compound against flaviviruses.