@article{3ebfc0e8c6504795874f4dec0fc20507,
title = "Erythrosin B is a potent and broad-spectrum orthosteric inhibitor of the flavivirus NS2B-NS3 protease",
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-Barr{\'e} 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.",
keywords = "Antiviral, Dengue virus, Erythrosin B, Flavivirus, Protease inhibitor, Zika virus",
author = "Zhong Li and Srilatha Sakamuru and Ruili Huang and Matthew Brecher and Koetzner, {Cheri A.} and Jing Zhang and Haiying Chen and Qin, {Cheng feng} and Zhang, {Qing Yu} and Jia Zhou and Kramer, {Laura D.} and Menghang Xia and Hongmin Li",
note = "Funding Information: We thank J. Tang at the Wadsworth Center Tissue Culture Core facility for help with cell culture and K. McClive-Reed for helpful suggestions. We also thank other core facilities at the Wadsworth Center, including the Applied Genomic Technologies Core for DNA sequencing, the Advanced Light Microscopy Core for immunofluorescence imaging, and the Tissue Culture Core for media. M.B. was partially supported by the NIH Biodefense and Emerging Infectious Disease training grant AI055429 . This work was partially supported by the Wadsworth Center flavivirus drug discovery seed funding (H.L., N.B, and L.D.K.), by NIH grants AI133219 , AI134568 , and AI131669 (H.L., Q.Y.Z., and L.D.K.), by NIH grant DA038446 (J.Z.), and by the Intramural Research Program of NCATS, NIH (M.X.). C.F.Q. was supported by the NSFC Excellent Young Scientist (No. 81522025 ), Innovative Research Group (No. 81621005 ), the National Key Research and Development Project of China (No. 2016YFD0500304 ), the National Science and Technology Major Project of China (No. 2017ZX09101005 ), and the Newton Advanced Fellowship from the UK Academy of Medical Sciences ( NAF003\1003 ) and the NSFC of China (No. 81661130162 ). ",
year = "2018",
month = feb,
doi = "10.1016/j.antiviral.2017.12.018",
language = "English (US)",
volume = "150",
pages = "217--225",
journal = "Antiviral Research",
issn = "0166-3542",
publisher = "Elsevier",
}