Abstract
Mosquito transmitted viruses, particularly those of the genus Flavivirus, are a significant healthcare burden worldwide, especially in tropical and sub-tropical areas. However, effective medicines for these viral infections remains lacking. Berberine (BBR) is an alkaloid found in some plants used in traditional medicines in Southeast Asia and elsewhere, and BBR has been shown to possess anti-viral activities. During a screen for potential application to mosquito transmitted viruses, BBR was shown to have virucidal activity against dengue virus (DENV; IC50 42.87 µM) as well as against Zika virus (IC50 11.42 µM) and chikungunya virus (IC50 14.21 µM). BBR was shown to have cellular effects that lead to an increase in cellular DENV E protein without a concomitant effect on DENV nonstructural proteins, suggesting an effect on viral particle formation or egress. While BBR was shown to have an effect of ERK1/2 activation this did not result in defects in viral egress mechanisms. The primary effect of BBR on viral production was likely to be through BBR acting through AMPK activation and disruption of lipid metabolism. Combined these results suggest that BBR has a dual effect on DENV infection, and BBR may have the potential for development as an anti-DENV antiviral.
Highlights
The global threat from arthropod-borne viruses has become more serious due to dispersion of these viruses across continents
The viral titers were used to determine the IC50 values (Figure 1B) and the lowest IC50 calculated was for Zika virus (ZIKV) (11.42 μM), followed by chikungunya virus (CHIKV) (14.21 μM) and dengue virus (DENV) 2 (42.87 μM)
24After h cells24were collected and proteins proteins prepared and expression of phosphorylation status of AMPK (p-AMPK), total AMPK and GAPDH were determined by western blot analysis. pAMPK and total AMPK were detected on separate filters. (D) Band intensities were quantitated and normalized to GAPDH
Summary
The global threat from arthropod-borne viruses (arboviruses) has become more serious due to dispersion of these viruses across continents This is especially true for dengue virus (DENV; family Flaviviridae, genus Flavivirus) which has become distributed across more than 100 tropical and subtropical countries [1]. Other viruses in the Flavivirus genus that cause high hospitalizations and morbidity along with DENV include West Nile virus (WNV), yellow fever virus (YFV) and Japanese encephalitis virus (JEV) [2]. To combat these viruses there are only two safe and effective vaccines available for JEV and YFV [3], while an approved DENV vaccine has concerns with regards to both safety and efficacy [4,5]. The DENV virion is a spherical shaped enveloped virus, with surface proteins arranged in icosahedral symmetry containing a positive-sense single stranded RNA genome of approximately
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