Most flaviviruses are arthropod-borne viruses, transmitted by either ticks or mosquitoes, and cause morbidity and mortality worldwide. They are endemic in many countries and have recently emerged in new regions, such as the Zika virus (ZIKV) in South-and Central America, the West Nile virus (WNV) in North America, and the Yellow fever virus (YFV) in Brazil and many African countries, highlighting the need for preparedness. Currently, there are no antiviral drugs available to treat flavivirus infections. We have previously discovered a broad-spectrum antiviral compound, benzavir-2, with potent antiviral activity against both DNA- and RNA-viruses. Our purpose was to investigate the inhibitory activity of benzavir-2 against flaviviruses. We used a ZIKV ZsGreen-expressing vector, two lineages of wild-type ZIKV, and other medically important flaviviruses. Benzavir-2 inhibited ZIKV derived reporter gene expression with an EC50 value of 0.8 ± 0.1 µM. Furthermore, ZIKV plaque formation, progeny virus production, and viral RNA expression were strongly inhibited. In addition, 2.5 µM of benzavir-2 reduced infection in vitro in three to five orders of magnitude for five other flaviviruses: WNV, YFV, the tick-borne encephalitis virus, Japanese encephalitis virus, and dengue virus. In conclusion, benzavir-2 was a potent inhibitor of flavivirus infection, which supported the broad-spectrum antiviral activity of benzavir-2.

中文翻译：

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Benzavir-2对新兴黄病毒的抗病毒活性。

大多数黄病毒是节肢动物传播的病毒，通过壁虱或蚊子传播，并导致全世界的发病率和死亡率。它们在许多国家都很流行，最近又出现在新的地区，例如南美和中美洲的寨卡病毒（ZIKV），北美的西尼罗河病毒（WNV）和巴西的黄热病病毒（YFV）和许多非洲国家，强调了备灾的必要性。当前，没有抗病毒药物可用于治疗黄病毒感染。我们以前已经发现了广谱抗病毒化合物benzavir-2，它对DNA和RNA病毒均具有有效的抗病毒活性。我们的目的是研究benzavir-2对黄病毒的抑制活性。我们使用了ZIKV ZsGreen表达载体，两个野生型ZIKV谱系，和其他医学上重要的黄病毒。Benzavir-2抑制ZIKV衍生的报告基因表达，EC50值为0.8±0.1 µM。此外，ZIKV斑块的形成，子代病毒的产生和病毒RNA的表达都受到强烈抑制。此外，2.5 µM的benzavir-2可以在三到五个数量级上减少其他五种黄病毒的体外感染：WNV，YFV，tick传脑炎病毒，日本脑炎病毒和登革热病毒。总之，benzavir-2是黄病毒感染的有效抑制剂，支持benzavir-2的广谱抗病毒活性。5 µM的benzavir-2可以将三种其他黄病毒（WNV，YFV，the传脑炎病毒，日本脑炎病毒和登革热病毒）的体外感染减少三到五个数量级。总之，benzavir-2是黄病毒感染的有效抑制剂，支持benzavir-2的广谱抗病毒活性。5 µM的benzavir-2可以将三种其他黄病毒（WNV，YFV，the传脑炎病毒，日本脑炎病毒和登革热病毒）的体外感染减少三到五个数量级。总之，benzavir-2是黄病毒感染的有效抑制剂，支持benzavir-2的广谱抗病毒活性。