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Erythrosin B is a potent and broad-spectrum orthosteric inhibitor of the flavivirus NS2B-NS3 protease
Antiviral Research ( IF 7.6 ) Pub Date : 2017-12-27 , DOI: 10.1016/j.antiviral.2017.12.018
Zhong Li , Srilatha Sakamuru , Ruili Huang , Matthew Brecher , Cheri A. Koetzner , Jing Zhang , Haiying Chen , Cheng-feng Qin , Qing-Yu Zhang , Jia Zhou , Laura D. Kramer , Menghang Xia , Hongmin Li

Many flaviviruses, such as Zika virus (ZIKV), Dengue virus (DENV1-4) and yellow fever virus (YFV), are significant human pathogens. Infection with ZIKV, an emerging mosquito-borne flavivirus, is associated with increased risk of microcephaly in newborns and Guillain-Barré syndrome and other complications in adults. Currently, specific therapy does not exist for any flavivirus infections. In this study, we found that erythrosin B, an FDA-approved food additive, is a potent inhibitor for flaviviruses, including ZIKV and DENV2. Erythrosin B was found to inhibit the DENV2 and ZIKV NS2B-NS3 proteases with IC50 in low micromolar range, via a non-competitive mechanism. Erythrosin B can significantly reduce titers of representative flaviviruses, DENV2, ZIKV, YFV, JEV, and WNV, with micromolar potency and with excellent cytotoxicity profile. Erythrosin B can also inhibit ZIKV replication in ZIKV-relevant human placental and neural progenitor cells. As a pregnancy category B food additive, erythrosin B may represent a promising and easily developed therapy for management of infections by ZIKV and other flaviviruses.



中文翻译:

Erosthrosin B是黄病毒NS2B-NS3蛋白酶的有效且广谱正构抑制剂

许多黄病毒,例如寨卡病毒(ZIKV),登革热病毒(DENV1-4)和黄热病病毒(YFV),都是重要的人类病原体。ZIKV(一种新兴的蚊媒黄病毒)感染与新生儿小头畸形和格林-巴利综合症(Guillain-Barrésyndrome)以及成人的其他并发症的风险增加有关。目前,尚不存在针对任何黄病毒感染的特异性疗法。在这项研究中,我们发现erythrosin B是FDA批准的食品添加剂,是黄病毒(包括ZIKV和DENV2)的有效抑制剂。发现赤藓红B通过低微摩尔范围的IC 50抑制DENV2和ZIKV NS2B-NS3蛋白酶非竞争性机制。Erosthrosin B可显着降低代表性黄病毒DENV2,ZIKV,YFV,JEV和WNV的滴度,具有微摩尔效价并具有出色的细胞毒性谱。Erosthrosin B还可以抑制ZIKV相关人类胎盘和神经祖细胞中的ZIKV复制。作为妊娠B类食品添加剂,赤藓红B可能代表一种有前途且易于开发的治疗ZIKV和其他黄病毒感染的疗法。

更新日期:2017-12-27
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