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.

• Authors: 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
• Journal: Cell discovery (Cell Discov) Vol. 4 Pg. 31 ( 2018) ISSN: 2056-5968 [Print] England
• PMID: 29872540 (Publication Type: Journal Article)