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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 \u00b5M) as well as against Zika virus (IC50 11.42 \u00b5M) and chikungunya virus (IC50 14.21 \u00b5M). 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.<\/jats:p>","DOI":"10.3390\/molecules26185501","type":"journal-article","created":{"date-parts":[[2021,9,12]],"date-time":"2021-09-12T21:45:57Z","timestamp":1631483157000},"page":"5501","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Berberine Inhibits Dengue Virus through Dual Mechanisms"],"prefix":"10.3390","volume":"26","author":[{"given":"Thippayawan","family":"Ratanakomol","sequence":"first","affiliation":[{"name":"Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom 73170, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3696-8390","authenticated-orcid":false,"given":"Sittiruk","family":"Roytrakul","sequence":"additional","affiliation":[{"name":"National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Rangsit 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitwara","family":"Wikan","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom 73170, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6592-9852","authenticated-orcid":false,"given":"Duncan R.","family":"Smith","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom 73170, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/nature12060","article-title":"The global distribution and burden of dengue","volume":"496","author":"Bhatt","year":"2013","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/S0140-6736(08)60238-X","article-title":"Pathogenic flaviviruses","volume":"371","author":"Gould","year":"2008","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.idc.2004.11.004","article-title":"Yellow fever and Japanese encephalitis vaccines: Indications and complications","volume":"19","author":"Marfin","year":"2005","journal-title":"Infect. 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