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

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

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)217-225
Number of pages9
JournalAntiviral Research
Volume150
DOIs
StatePublished - Feb 1 2018

Fingerprint

Erythrosine
Flavivirus
Peptide Hydrolases
Yellow fever virus
Food Additives
Flavivirus Infections
Microcephaly
Dengue Virus
Virus Replication
Culicidae
Inhibitory Concentration 50
Zika Virus
Stem Cells
Pregnancy
Therapeutics

Keywords

  • Antiviral
  • Dengue virus
  • Erythrosin B
  • Flavivirus
  • Protease inhibitor
  • Zika virus

ASJC Scopus subject areas

  • Pharmacology
  • Virology

Cite this

Li, Z., Sakamuru, S., Huang, R., Brecher, M., Koetzner, C. A., Zhang, J., ... Li, H. (2018). Erythrosin B is a potent and broad-spectrum orthosteric inhibitor of the flavivirus NS2B-NS3 protease. Antiviral Research, 150, 217-225. https://doi.org/10.1016/j.antiviral.2017.12.018

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 journalArticle

Li, Z, Sakamuru, S, Huang, R, Brecher, M, Koetzner, CA, Zhang, J, Chen, H, Qin, CF, Zhang, QY, Zhou, J, Kramer, LD, Xia, M & Li, H 2018, 'Erythrosin B is a potent and broad-spectrum orthosteric inhibitor of the flavivirus NS2B-NS3 protease', Antiviral Research, vol. 150, pp. 217-225. https://doi.org/10.1016/j.antiviral.2017.12.018
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. / Erythrosin B is a potent and broad-spectrum orthosteric inhibitor of the flavivirus NS2B-NS3 protease. In: Antiviral Research. 2018 ; Vol. 150. pp. 217-225.
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