Emetine inhibits Zika and Ebola virus infections through two molecular mechanisms: inhibiting viral replication and decreasing viral entry
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 nanomola...
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| Veröffentlicht in: | Cell discovery 2018-06, Vol.4 (1), p.31-14, Article 31 |
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| creator | Yang, Shu Xu, Miao Lee, Emily M Gorshkov, Kirill Shiryaev, Sergey A. He, Shihua Sun, Wei Cheng, Yu-Shan Hu, Xin Tharappel, Anil Mathew Lu, Billy Pinto, Antonella Farhy, Chen Huang, Chun-Teng Zhang, Zirui Zhu, Wenjun Wu, Yuying Zhou, Yi Song, Guang Zhu, Heng Shamim, Khalida Martínez-Romero, Carles García-Sastre, Adolfo Preston, Richard A. Jayaweera, Dushyantha T. Huang, Ruili Huang, Wenwei Xia, Menghang Simeonov, Anton Ming, Guoli Qiu, Xiangguo Terskikh, Alexey V. Tang, Hengli Song, Hongjun Zheng, Wei |
| description | 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 (IC
50
) 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. |
| doi_str_mv | 10.1038/s41421-018-0034-1 |
| format | Article |
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50
) 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.</description><identifier>ISSN: 2056-5968</identifier><identifier>EISSN: 2056-5968</identifier><identifier>DOI: 10.1038/s41421-018-0034-1</identifier><identifier>PMID: 29872540</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/80/304 ; 631/80/86 ; Biomedical and Life Sciences ; Cell Biology ; Cell Culture ; Cell Cycle Analysis ; Cell Physiology ; Ebola virus ; Ebolavirus ; Emetine ; Life Sciences ; Molecular modelling ; Public health ; Stem Cells ; Zika virus</subject><ispartof>Cell discovery, 2018-06, Vol.4 (1), p.31-14, Article 31</ispartof><rights>The Author(s) 2018</rights><rights>2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-c478c8184d2ae75e3d6b80a08b3df2133546633a1eb46ae3e34350498aa6b24e3</citedby><cites>FETCH-LOGICAL-c470t-c478c8184d2ae75e3d6b80a08b3df2133546633a1eb46ae3e34350498aa6b24e3</cites><orcidid>0000-0002-4652-8818 ; 0000-0003-1034-0757 ; 0000-0002-8426-2889 ; 0000-0002-2517-6075</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5986771/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5986771/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27923,27924,41119,42188,51575,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29872540$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yang, Shu</creatorcontrib><creatorcontrib>Xu, Miao</creatorcontrib><creatorcontrib>Lee, Emily M</creatorcontrib><creatorcontrib>Gorshkov, Kirill</creatorcontrib><creatorcontrib>Shiryaev, Sergey A.</creatorcontrib><creatorcontrib>He, Shihua</creatorcontrib><creatorcontrib>Sun, Wei</creatorcontrib><creatorcontrib>Cheng, Yu-Shan</creatorcontrib><creatorcontrib>Hu, Xin</creatorcontrib><creatorcontrib>Tharappel, Anil Mathew</creatorcontrib><creatorcontrib>Lu, Billy</creatorcontrib><creatorcontrib>Pinto, Antonella</creatorcontrib><creatorcontrib>Farhy, Chen</creatorcontrib><creatorcontrib>Huang, Chun-Teng</creatorcontrib><creatorcontrib>Zhang, Zirui</creatorcontrib><creatorcontrib>Zhu, Wenjun</creatorcontrib><creatorcontrib>Wu, Yuying</creatorcontrib><creatorcontrib>Zhou, Yi</creatorcontrib><creatorcontrib>Song, Guang</creatorcontrib><creatorcontrib>Zhu, Heng</creatorcontrib><creatorcontrib>Shamim, Khalida</creatorcontrib><creatorcontrib>Martínez-Romero, Carles</creatorcontrib><creatorcontrib>García-Sastre, Adolfo</creatorcontrib><creatorcontrib>Preston, Richard A.</creatorcontrib><creatorcontrib>Jayaweera, Dushyantha T.</creatorcontrib><creatorcontrib>Huang, Ruili</creatorcontrib><creatorcontrib>Huang, Wenwei</creatorcontrib><creatorcontrib>Xia, Menghang</creatorcontrib><creatorcontrib>Simeonov, Anton</creatorcontrib><creatorcontrib>Ming, Guoli</creatorcontrib><creatorcontrib>Qiu, Xiangguo</creatorcontrib><creatorcontrib>Terskikh, Alexey V.</creatorcontrib><creatorcontrib>Tang, Hengli</creatorcontrib><creatorcontrib>Song, Hongjun</creatorcontrib><creatorcontrib>Zheng, Wei</creatorcontrib><title>Emetine inhibits Zika and Ebola virus infections through two molecular mechanisms: inhibiting viral replication and decreasing viral entry</title><title>Cell discovery</title><addtitle>Cell Discov</addtitle><addtitle>Cell Discov</addtitle><description>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 (IC
50
) 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.</description><subject>631/80/304</subject><subject>631/80/86</subject><subject>Biomedical and Life Sciences</subject><subject>Cell Biology</subject><subject>Cell Culture</subject><subject>Cell Cycle Analysis</subject><subject>Cell Physiology</subject><subject>Ebola virus</subject><subject>Ebolavirus</subject><subject>Emetine</subject><subject>Life Sciences</subject><subject>Molecular modelling</subject><subject>Public health</subject><subject>Stem Cells</subject><subject>Zika 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Adolfo</au><au>Preston, Richard A.</au><au>Jayaweera, Dushyantha T.</au><au>Huang, Ruili</au><au>Huang, Wenwei</au><au>Xia, Menghang</au><au>Simeonov, Anton</au><au>Ming, Guoli</au><au>Qiu, Xiangguo</au><au>Terskikh, Alexey V.</au><au>Tang, Hengli</au><au>Song, Hongjun</au><au>Zheng, Wei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Emetine inhibits Zika and Ebola virus infections through two molecular mechanisms: inhibiting viral replication and decreasing viral entry</atitle><jtitle>Cell discovery</jtitle><stitle>Cell Discov</stitle><addtitle>Cell Discov</addtitle><date>2018-06-05</date><risdate>2018</risdate><volume>4</volume><issue>1</issue><spage>31</spage><epage>14</epage><pages>31-14</pages><artnum>31</artnum><issn>2056-5968</issn><eissn>2056-5968</eissn><abstract>The re-emergence of Zika virus (ZIKV) and Ebola virus (EBOV) poses serious and continued threats to the global public health. 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50
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| source | DOAJ Directory of Open Access Journals; Springer Nature OA Free Journals; Nature Free; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | 631/80/304 631/80/86 Biomedical and Life Sciences Cell Biology Cell Culture Cell Cycle Analysis Cell Physiology Ebola virus Ebolavirus Emetine Life Sciences Molecular modelling Public health Stem Cells Zika virus |
| title | Emetine inhibits Zika and Ebola virus infections through two molecular mechanisms: inhibiting viral replication and decreasing viral entry |
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