Journal
ANTIVIRAL RESEARCH
Volume 150, Issue -, Pages 217-225Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.antiviral.2017.12.018
Keywords
Flavivirus; Zika virus; Dengue virus; Antiviral; Protease inhibitor; Erythrosin B
Categories
Funding
- NIH Biodefense and Emerging Infectious Disease training grant [AI055429]
- Wadsworth Center flavivirus drug discovery seed funding
- NIH [AI133219, AI134568, AI131669, DA038446]
- Intramural Research Program of NCATS, NIH
- NSFC Excellent Young Scientist [81522025]
- Innovative Research Group [81621005]
- National Key Research and Development Project of China [2016YFD0500304]
- National Science and Technology Major Project of China [2017ZX09101005]
- Newton Advanced Fellowship from the UK Academy of Medical Sciences [NAF003\1003]
- NSFC of China [81661130162]
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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-Barre 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 noncompetitive 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.
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