Emetine inhibits Zika and Ebola virus infections through two molecular mechanisms: inhibiting viral replication and decreasing viral entry

被引：125

作者：

Yang, Shu ^{[1
]}

Xu, Miao ^{[1
]}

Lee, Emily M. ^{[2
]}

Gorshkov, Kirill ^{[1
]}

Shiryaev, Sergey A. ^{[3
]}

He, Shihua ^{[4
]}

Sun, Wei ^{[1
]}

Cheng, Yu-Shan ^{[1
]}

Hu, Xin ^{[1
]}

Tharappel, Anil Mathew ^{[2
]}

Lu, Billy ^{[1
]}

Pinto, Antonella ^{[3
]}

Farhy, Chen ^{[3
]}

Huang, Chun-Teng ^{[3
]}

Zhang, Zirui ^{[4
]}

Zhu, Wenjun ^{[4
]}

Wu, Yuying ^{[5
]}

Zhou, Yi ^{[5
]}

Song, Guang ^{[6
]}

Zhu, Heng ^{[6
]}

Shamim, Khalida ^{[1
]}

Martinez-Romero, Carles ^{[7
,8
]}

Garcia-Sastre, Adolfo ^{[7
,8
]}

Preston, Richard A. ^{[9
]}

Jayaweera, Dushyantha T. ^{[9
]}

Huang, Ruili ^{[1
]}

Huang, Wenwei ^{[1
]}

Xia, Menghang ^{[1
]}

Simeonov, Anton ^{[1
]}

Ming, Guoli ^{[10
,11
]}

Qiu, Xiangguo ^{[4
,12
]}

Terskikh, Alexey, V ^{[3
]}

Tang, Hengli ^{[2
]}

Song, Hongjun ^{[10
,11
]}

Zheng, Wei ^{[1
]}

机构：

[1] NIH, Natl Ctr Advancing Translat Sci, 9800 Med Ctr Dr, Bethesda, MD 20892 USA

[2] Florida State Univ, Dept Biol Sci, Tallahassee, FL 32306 USA

[3] Sanford Burnham Prebys Med Discovery Inst, Dev Aging & Regenerat Program, La Jolla, CA 92037 USA

[4] Publ Hlth Agcy Canada, Natl Microbiol Lab, Special Pathogens Program, Winnipeg, MB R3E 3R2, Canada

[5] Florida State Univ, Dept Biomed Sci, Tallahassee, FL 32306 USA

[6] Johns Hopkins Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD USA

[7] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA

[8] Icahn Sch Med Mt Sinai, Global Hlth & Emerging Pathogens Inst, New York, NY 10029 USA

[9] Univ Miami, Miller Sch Med, Dept Med, Miami, FL 33136 USA

[10] Univ Penn, Dept Neurosci, Philadelphia, PA 19104 USA

[11] Univ Penn, Mahoney Inst Neurosci, Philadelphia, PA 19104 USA

[12] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB R3E 0J9, Canada

来源：

CELL DISCOVERY | 2018年 / 4卷

关键词：

NIEMANN-PICK C1; REPURPOSING SCREEN; IDENTIFICATION; CARDIOTOXICITY; MODELS; SYSTEM; DENGUE; ASSAY; RNA;

D O I：

10.1038/s41421-018-0034-1

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

The re-emergence of Zika virus (ZIKV) and Ebola virus (EBOV) poses serious and continued threats to the global public health. Effective therapeutics for these maladies is an unmet need. Here, we show that emetine, an anti-protozoal agent, potently inhibits ZIKV and EBOV infection with a low nanomolar half maximal inhibitory concentration (IC50) in vitro and potent activity in vivo. Two mechanisms of action for emetine are identified: the inhibition of ZIKV NS5 polymerase activity and disruption of lysosomal function. Emetine also inhibits EBOV entry. Cephaeline, a desmethyl analog of emetine, which may be better tolerated in patients than emetine, exhibits a similar efficacy against both ZIKV and EBOV infections. Hence, emetine and cephaeline offer pharmaceutical therapies against both ZIKV and EBOV infection.

引用

页数：14

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