期刊
CELL DISCOVERY
卷 4, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41421-018-0034-1
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资金
- Intramural Research Programs of the National Center for Advancing Translational Sciences
- National Institute of Allergy and Infectious Diseases
- Public Health Agency of Canada
- NIH [U19 AI109762-1, R01AI079110, R01AI089539, R35NS097370, U19AI131130, R37NS047344, R21NS100477]
- CIHR [IER-143487]
- Spotlight Innovation Inc, IA, USA
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.
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