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

Shu Yang; Miao Xu; Emily M. Lee; Kirill Gorshkov; Sergey A. Shiryaev; Shihua He; Wei Sun; Yu Shan Cheng; Xin Hu; Anil Mathew Tharappel; Billy Lu; Antonella Pinto; Chen Farhy; Chun Teng Huang; Zirui Zhang; Wenjun Zhu; Yuying Wu; Yi Zhou; Guang Song; Heng Zhu; Khalida Shamim; Carles Martínez-Romero; Adolfo García-Sastre; Richard A. Preston; Dushyantha T. Jayaweera; Ruili Huang; Wenwei Huang; Menghang Xia; Anton Simeonov; Guoli Ming; Xiangguo Qiu; Alexey V. Terskikh; Hengli Tang; Hongjun Song; Wei Zheng

doi:10.1038/s41421-018-0034-1

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

Shu Yang, Miao Xu, Emily M. Lee, Kirill Gorshkov, Sergey A. Shiryaev, Shihua He, Wei Sun, Yu Shan Cheng, Xin Hu, Anil Mathew Tharappel, Billy Lu, Antonella Pinto, Chen Farhy, Chun Teng Huang, Zirui Zhang, Wenjun Zhu, Yuying Wu, Yi Zhou, Guang Song, Heng ZhuKhalida Shamim, Carles Martínez-Romero, Adolfo García-Sastre, Richard A. Preston, Dushyantha T. Jayaweera, Ruili Huang, Wenwei Huang, Menghang Xia, Anton Simeonov, Guoli Ming, Xiangguo Qiu, Alexey V. Terskikh, Hengli Tang, Hongjun Song, Wei Zheng

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Abstract

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.

Original language	English
Article number	31
Journal	Cell Discovery
Volume	4
Issue number	1
DOIs	https://doi.org/10.1038/s41421-018-0034-1
State	Published - 1 Dec 2018

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Yang, S., Xu, M., Lee, E. M., Gorshkov, K., Shiryaev, S. A., He, S., Sun, W., Cheng, Y. S., Hu, X., Tharappel, A. M., Lu, B., Pinto, A., Farhy, C., Huang, C. T., Zhang, Z., Zhu, W., Wu, Y., Zhou, Y., Song, G., ... Zheng, W. (2018). Emetine inhibits Zika and Ebola virus infections through two molecular mechanisms: Inhibiting viral replication and decreasing viral entry. Cell Discovery, 4(1), Article 31. https://doi.org/10.1038/s41421-018-0034-1

@article{e1415d1fbc5346c0be7c29192a81773b,

title = "Emetine inhibits Zika and Ebola virus infections through two molecular mechanisms: Inhibiting viral replication and decreasing viral entry",

abstract = "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.",

author = "Shu Yang and Miao Xu and Lee, {Emily M.} and Kirill Gorshkov and Shiryaev, {Sergey A.} and Shihua He and Wei Sun and Cheng, {Yu Shan} and Xin Hu and Tharappel, {Anil Mathew} and Billy Lu and Antonella Pinto and Chen Farhy and Huang, {Chun Teng} and Zirui Zhang and Wenjun Zhu and Yuying Wu and Yi Zhou and Guang Song and Heng Zhu and Khalida Shamim and Carles Mart{\'i}nez-Romero and Adolfo Garc{\'i}a-Sastre and Preston, {Richard A.} and Jayaweera, {Dushyantha T.} and Ruili Huang and Wenwei Huang and Menghang Xia and Anton Simeonov and Guoli Ming and Xiangguo Qiu and Terskikh, {Alexey V.} and Hengli Tang and Hongjun Song and Wei Zheng",

note = "Publisher Copyright: {\textcopyright} 2018 The Author(s).",

year = "2018",

month = dec,

day = "1",

doi = "10.1038/s41421-018-0034-1",

language = "English",

volume = "4",

journal = "Cell Discovery",

issn = "2056-5968",

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Yang, S, Xu, M, Lee, EM, Gorshkov, K, Shiryaev, SA, He, S, Sun, W, Cheng, YS, Hu, X, Tharappel, AM, Lu, B, Pinto, A, Farhy, C, Huang, CT, Zhang, Z, Zhu, W, Wu, Y, Zhou, Y, Song, G, Zhu, H, Shamim, K, Martínez-Romero, C, García-Sastre, A, Preston, RA, Jayaweera, DT, Huang, R, Huang, W, Xia, M, Simeonov, A, Ming, G, Qiu, X, Terskikh, AV, Tang, H, Song, H & Zheng, W 2018, 'Emetine inhibits Zika and Ebola virus infections through two molecular mechanisms: Inhibiting viral replication and decreasing viral entry', Cell Discovery, vol. 4, no. 1, 31. https://doi.org/10.1038/s41421-018-0034-1

TY - JOUR

T1 - Emetine inhibits Zika and Ebola virus infections through two molecular mechanisms

T2 - Inhibiting viral replication and decreasing viral entry

AU - Yang, Shu

AU - Xu, Miao

AU - Lee, Emily M.

AU - Gorshkov, Kirill

AU - Shiryaev, Sergey A.

AU - He, Shihua

AU - Sun, Wei

AU - Cheng, Yu Shan

AU - Hu, Xin

AU - Tharappel, Anil Mathew

AU - Lu, Billy

AU - Pinto, Antonella

AU - Farhy, Chen

AU - Huang, Chun Teng

AU - Zhang, Zirui

AU - Zhu, Wenjun

AU - Wu, Yuying

AU - Zhou, Yi

AU - Song, Guang

AU - Zhu, Heng

AU - Shamim, Khalida

AU - Martínez-Romero, Carles

AU - García-Sastre, Adolfo

AU - Preston, Richard A.

AU - Jayaweera, Dushyantha T.

AU - Huang, Ruili

AU - Huang, Wenwei

AU - Xia, Menghang

AU - Simeonov, Anton

AU - Ming, Guoli

AU - Qiu, Xiangguo

AU - Terskikh, Alexey V.

AU - Tang, Hengli

AU - Song, Hongjun

AU - Zheng, Wei

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85048122680&partnerID=8YFLogxK

U2 - 10.1038/s41421-018-0034-1

DO - 10.1038/s41421-018-0034-1

M3 - Article

AN - SCOPUS:85048122680

SN - 2056-5968

VL - 4

JO - Cell Discovery

JF - Cell Discovery

IS - 1

M1 - 31

ER -

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

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