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
N1 - Funding Information:
We thank Egan Sanchez and Jennifer Jallo from the Tang lab for technical assistance. We also thank DeeAnn Visk for careful editing of this mansucript. This work was supported by the Intramural Research Programs of the National Center for Advancing Translational Sciences and the National Institute of Allergy and Infectious Diseases (W.Z.), Public Health Agency of Canada (X.Q.), NIH grant U19 AI109762-1(X.Q.), CIHR IER-143487 (X.Q), NIH grants of R01AI079110 and R01AI089539 (A.G.), NIH grants R35NS097370 (G.M.), U19AI131130 (G.M. and H.T.), and R37NS047344 (H.S.), R21NS100477 (A.V.T.). The study is also partially supported by Spotlight Innovation Inc, IA, USA. (H.T.) 1National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Bethesda, MD 20892, USA. 2Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA. 3Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA. 4Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada. 5Department of Biomedical Sciences, Florida State University, Tallahassee, FL 32306, USA. 6Department of Pharmacology & Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA. 7Department of Microbiology and Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. 8Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL 33136, USA. 9Department of Neuroscience and Mahoney Institute for Neurosciences, University of Pennsylvania, Philadelphia, PA 19104, USA. 10Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada
Funding Information:
We thank Egan Sanchez and Jennifer Jallo from the Tang lab for technical assistance. We also thank DeeAnn Visk for careful editing of this mansucript. This work was supported by the Intramural Research Programs of the National Center for Advancing Translational Sciences and the National Institute of Allergy and Infectious Diseases (W.Z.), Public Health Agency of Canada (X.Q.), NIH grant U19 AI109762-1(X.Q.), CIHR IER-143487 (X.Q), NIH grants of R01AI079110 and R01AI089539 (A.G.), NIH grants R35NS097370 (G.M.), U19AI131130 (G.M. and H.T.), and R37NS047344 (H.S.), R21NS100477 (A.V.T.). The study is also partially supported by Spotlight Innovation Inc, IA, USA. (H.T.)
Publisher Copyright:
© 2018 The Author(s).
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 -