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 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 217-225 |
| Number of pages | 9 |
| Journal | Antiviral Research |
| Volume | 150 |
| DOIs | |
| State | Published - Feb 1 2018 |
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Keywords
- Antiviral
- Dengue virus
- Erythrosin B
- Flavivirus
- Protease inhibitor
- Zika virus
ASJC Scopus subject areas
- Pharmacology
- Virology
Cite this
Erythrosin B is a potent and broad-spectrum orthosteric inhibitor of the flavivirus NS2B-NS3 protease. / Li, Zhong; Sakamuru, Srilatha; Huang, Ruili; Brecher, Matthew; Koetzner, Cheri A.; Zhang, Jing; Chen, Haiying; Qin, Cheng feng; Zhang, Qing Yu; Zhou, Jia; Kramer, Laura D.; Xia, Menghang; Li, Hongmin.
In: Antiviral Research, Vol. 150, 01.02.2018, p. 217-225.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Erythrosin B is a potent and broad-spectrum orthosteric inhibitor of the flavivirus NS2B-NS3 protease
AU - Li, Zhong
AU - Sakamuru, Srilatha
AU - Huang, Ruili
AU - Brecher, Matthew
AU - Koetzner, Cheri A.
AU - Zhang, Jing
AU - Chen, Haiying
AU - Qin, Cheng feng
AU - Zhang, Qing Yu
AU - Zhou, Jia
AU - Kramer, Laura D.
AU - Xia, Menghang
AU - Li, Hongmin
PY - 2018/2/1
Y1 - 2018/2/1
N2 - 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.
AB - 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.
KW - Antiviral
KW - Dengue virus
KW - Erythrosin B
KW - Flavivirus
KW - Protease inhibitor
KW - Zika virus
UR - http://www.scopus.com/inward/record.url?scp=85040255497&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85040255497&partnerID=8YFLogxK
U2 - 10.1016/j.antiviral.2017.12.018
DO - 10.1016/j.antiviral.2017.12.018
M3 - Article
VL - 150
SP - 217
EP - 225
JO - Antiviral Research
JF - Antiviral Research
SN - 0166-3542
ER -