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Cited by 641

The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.

Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen

Open access
Xu, Miao, Lee, Emily M, Wen, Zhexing, Cheng, Yichen, Huang, Wei-Kai, Qian, Xuyu, TCW, Julia, Kouznetsova, Jennifer, Ogden, Sarah C, Hammack, Christy, Jacob, Fadi, Nguyen, Ha Nam, Itkin, Misha, Hanna, Catherine, Shinn, Paul, Allen, Chase, Michael, Samuel G, Simeonov, Anton, Huang, Wenwei, Christian, Kimberly M, Goate, Alison, Brennand, Kristen J, Huang, Ruili, Xia, Menghang, Ming, Guo-li, Zheng, Wei, Song, Hongjun, Tang, Hengli·2016·Nature Medicine
DOI 10.1038/nm.4184
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Abstract

In response to the current global health emergency posed by the Zika virus (ZIKV) outbreak and its link to microcephaly and other neurological conditions, we performed a drug repurposing screen of ∼6,000 compounds that included approved drugs, clinical trial drug candidates and pharmacologically active compounds; we identified compounds that either inhibit ZIKV infection or suppress infection-induced caspase-3 activity in different neural cells. A pan-caspase inhibitor, emricasan, inhibited ZIKV-induced increases in caspase-3 activity and protected human cortical neural progenitors in both monolayer and three-dimensional organoid cultures. Ten structurally unrelated inhibitors of cyclin-dependent kinases inhibited ZIKV replication. Niclosamide, a category B anthelmintic drug approved by the US Food and Drug Administration, also inhibited ZIKV replication. Finally, combination treatments using one compound from each category (neuroprotective and antiviral) further increased protection of human neural progenitors and astrocytes from ZIKV-induced cell death. Our results demonstrate the efficacy of this screening strategy and identify lead compounds for anti-ZIKV drug development.

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Metadata

Authors
Xu, M., Lee, E. M., Wen, Z., Cheng, Y., Huang, W.-K., Qian, X., TCW, J., Kouznetsova, J., Ogden, S. C., Hammack, C., Jacob, F., Nguyen, H. N., Itkin, M., Hanna, C., Shinn, P., Allen, C., Michael, S. G., Simeonov, A., Huang, W., Christian, K. M., Goate, A., Brennand, K. J., Huang, R., Xia, M., Ming, G.-L., Zheng, W., Song, H., & Tang, H.
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2016-08-29
Volume
22
Issue
10
Pages
1101-1107
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/nm.4184
OpenAlex
W2514790758
Cited by
641
References
61
FWCI
92.80
Type
journal article
Language
en
Open access
hybrid

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