Evidence map›Paper›PMID 27571349›Full record

ArticleNature medicine2016

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

Miao Xu, Emily M Lee, Zhexing Wen, Yichen Cheng, Wei-Kai Huang, Xuyu Qian, Julia Tcw, Jennifer Kouznetsova, Sarah C Ogden, Christy Hammack and 18 more

Open access · hybridAbstract read
In one paragraph

Article in Nature medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 378 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
378citing papers in PubMed, 4 pooled it
96.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

378 citing papers in PubMed, 4 syntheses or guidelines pooled it, 662 citations in OpenAlex.

  1. Pooled it
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  8. New developments and applications of human organoids.Nature reviews. Molecular cell biology · 2026
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318 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

28 authors at 6 institutions in 2 countries.

Miao XuNational Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, USA.
Emily M LeeDepartment of Biological Science, Florida State University, Tallahassee, Florida, USA.
Zhexing WenDepartment of Psychiatry and Behavioral Science, Emory University School of Medicine, Atlanta, Georgia, USA.
Yichen ChengDepartment of Biological Science, Florida State University, Tallahassee, Florida, USA.
Wei-Kai HuangInstitute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Xuyu QianInstitute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Julia TcwDepartment of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Jennifer KouznetsovaNational Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, USA.
Sarah C OgdenDepartment of Biological Science, Florida State University, Tallahassee, Florida, USA.
Christy HammackDepartment of Biological Science, Florida State University, Tallahassee, Florida, USA.
Fadi JacobInstitute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Ha Nam NguyenInstitute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Misha ItkinNational Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, USA.
Catherine HannaDepartment of Biological Science, Florida State University, Tallahassee, Florida, USA.
Paul ShinnNational Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, USA.
Chase AllenDepartment of Biological Science, Florida State University, Tallahassee, Florida, USA.
Samuel G MichaelNational Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, USA.
Anton SimeonovNational Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, USA.
Wenwei HuangNational Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, USA.
Kimberly M ChristianInstitute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Alison GoateDepartment of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Kristen J BrennandDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Ruili HuangNational Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, USA.
Menghang XiaNational Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, USA.
Guo-Li MingInstitute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Wei ZhengNational Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, USA.
Hongjun SongInstitute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Hengli TangDepartment of Biological Science, Florida State University, Tallahassee, Florida, USA.
Florida State University · USJohns Hopkins University · USNational Center for Advancing Translational Sciences · USNational Institutes of Health · USIcahn School of Medicine at Mount Sinai · USJohns Hopkins Medicine · US

Funding

Research Services Section (RSS)ZICTR000242 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI WILSON, KELLI · 2015 to 2025
$64.9M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007309 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI COX, ANDREA L · 1985 to 2019
$43.2M
VESICULAR LOCALIZATION AND FUNCTION OF PRESENILIN 1 FRAGMENTP50AG005138 · NIA · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI SCHIMMING, CORBETT · 1985 to 2019
$37.9M
Integrative Network Biology Approaches to Identify, Characterize and Validate Molecular Subtypes in Alzheimer's DiseaseU01AG046170 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI EHRLICH, MICHELLE E, GANDY, SAMUEL E. · 2013 to 2022
$26.0M
Drug Repurposing Screening for Rare and Neglected DiseasesZIATR000018 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI ZHENG, WEI · 2015 to 2025
$24.6M
Role of CACNA1C - a shared risk gene in neuropsychiatric disordersU19MH106434 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI O'SHEA, K SUE SUE · 2016 to 2020
$13.8M
Training Program in Cellular and Molecular MedicineT32GM008752 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI RAO, RAJINI · 2000 to 2019
$11.7M
Higher Order Chromatin and Genetic Risk for SchizophreniaR01MH106056 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI AKBARIAN, SCHAHRAM, BRENNAND, KRISTEN JENNIFER · 2015 to 2023
$6.7M
INTERDISCIPLINARY TRAINING PROGRAM IN NEUROSCIENCEST32MH015330 · NIMH · JOHNS HOPKINS UNIVERSITY · PI MARGOLIS, RUSSELL L · 1985 to 2024
$6.2M
Drug Repurposing Screening for Zika Virus InfectionZIATR000269 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI ZHENG, WEI · 2016 to 2021
$6.1M
Translational models of neurodevelopmental epigenetics and disease using human iPSCsP01NS097206 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI HE, CHUAN · 2016 to 2020
$4.3M
Development of new neurons in the adult brainR01NS047344 · NINDS · JOHNS HOPKINS UNIVERSITY · PI SONG, HONGJUN · 2003 to 2011
$3.4M
Intramural NIH HHS ZIA TR000018Intramural NIH HHS ZIA TR000269NIAID NIH HHS R21 AI119530NIA NIH HHS P50 AG005138NIA NIH HHS U01 AG046170NIGMS NIH HHS T32 GM007309NIGMS NIH HHS T32 GM008752NIMH NIH HHS R01 MH101454NIMH NIH HHS R01 MH105128NIMH NIH HHS R01 MH106056NIMH NIH HHS R56 MH101454NIMH NIH HHS T32 MH015330NIMH NIH HHS U19 MH106434NINDS NIH HHS P01 NS097206NINDS NIH HHS R01 NS047344NINDS NIH HHS R01 NS048271NINDS NIH HHS R21 NS095348NINDS NIH HHS R37 NS047344NINDS NIH HHS R56 NS047344
6 · The paper itself

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.

Indexed as

AstrocytesBrainCaspase 3Caspase InhibitorsCell DeathCell LineDrug RepositioningHumansInduced Pluripotent Stem CellsMicrocephalyNeural Stem CellsNeuronsNiclosamideOrganoidsPentanoic AcidsVirus Replication3-(2-(2-tert-butylphenylaminooxalyl)aminopropionylamino)-4-oxo-5-(2,3,5,6-tetrafluorophenoxy)pentanoic acidCaspase 3Caspase InhibitorsNiclosamidePentanoic Acids

Identifiers

PMID27571349
PMCPMC5386783
OpenAlexW2514790758

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.