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赤藓红 B 是一种强效且广谱的黄病毒 NS2B-NS3 蛋白酶的正位变构抑制剂。

Erythrosin B is a potent and broad-spectrum orthosteric inhibitor of the flavivirus NS2B-NS3 protease.

机构信息

Wadsworth Center, New York State Department of Health, 120 New Scotland Ave, Albany, NY 12208, USA.

National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA.

出版信息

Antiviral Res. 2018 Feb;150:217-225. doi: 10.1016/j.antiviral.2017.12.018. Epub 2017 Dec 27.

DOI:10.1016/j.antiviral.2017.12.018
PMID:29288700
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5892443/
Abstract

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 IC 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.

摘要

许多黄病毒,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。感染寨卡病毒,一种新出现的蚊媒黄病毒,与新生儿小头畸形和吉兰-巴雷综合征以及成年人的其他并发症的风险增加有关。目前,还没有针对任何黄病毒感染的特定疗法。在这项研究中,我们发现,赤藓红 B,一种 FDA 批准的食品添加剂,是一种有效的黄病毒抑制剂,包括寨卡病毒和 DENV2。赤藓红 B 通过非竞争性机制,被发现可以抑制 DENV2 和 ZIKV NS2B-NS3 蛋白酶,其 IC 在低微摩尔范围内。赤藓红 B 可以显著降低代表性黄病毒、DENV2、ZIKV、YFV、JEV 和 WNV 的滴度,其效力为微摩尔级,且具有极好的细胞毒性特征。赤藓红 B 还可以抑制 ZIKV 在与寨卡病毒相关的人胎盘和神经祖细胞中的复制。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方法,可用于管理寨卡病毒和其他黄病毒的感染。

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