Evidence map›Paper›PMID 30081931›Full record

ArticleGenome medicine2018

A genome-wide siRNA screen identifies a druggable host pathway essential for the Ebola virus life cycle.

Scott Martin, Abhilash I Chiramel, Marie Luisa Schmidt, Yu-Chi Chen, Nadia Whitt, Ari Watt, Eric C Dunham, Kyle Shifflett, Shelby Traeger, Anne Leske and 13 more

Open access · goldAbstract read
In one paragraph

Article in Genome medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 1 pooled it
4.3field-weighted citation impact, top 5% 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

39 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.

  1. Pooled it
  2. Myricetin InhibitsCells · 2026
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  7. Reporter-expressing viruses for antiviral drug discovery research.Frontiers in cellular and infection microbiology · 2025
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  11. Frontiers in microbiology · 2024
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  13. NEmerging microbes & infections · 2023
    Article
  14. Review
  15. Article
  16. International journal of molecular sciences · 2023
    Article
  17. Article
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  19. Article
  20. Article
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

23 authors at 2 institutions in 2 countries.

Scott MartinDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, 31 Center Drive, Bethesda, MD, 20892, USA.
Abhilash I ChiramelLaboratory of Virology, Division of Intramural Research, National Institute for Allergy and Infectious Diseases, National Institutes of Health, 903 S 4th St., Hamilton, MT, 59840, USA.
Marie Luisa SchmidtInstitute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Südufer 10, 17493, Greifswald, Insel Riems, Germany.
Yu-Chi ChenDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, 31 Center Drive, Bethesda, MD, 20892, USA.
Nadia WhittDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, 31 Center Drive, Bethesda, MD, 20892, USA.
Ari WattLaboratory of Virology, Division of Intramural Research, National Institute for Allergy and Infectious Diseases, National Institutes of Health, 903 S 4th St., Hamilton, MT, 59840, USA.
Eric C DunhamLaboratory of Virology, Division of Intramural Research, National Institute for Allergy and Infectious Diseases, National Institutes of Health, 903 S 4th St., Hamilton, MT, 59840, USA.
Kyle ShifflettLaboratory of Virology, Division of Intramural Research, National Institute for Allergy and Infectious Diseases, National Institutes of Health, 903 S 4th St., Hamilton, MT, 59840, USA.
Shelby TraegerLaboratory of Virology, Division of Intramural Research, National Institute for Allergy and Infectious Diseases, National Institutes of Health, 903 S 4th St., Hamilton, MT, 59840, USA.
Anne LeskeJunior Research Group Arenavirus Biology, Friedrich-Loeffler-Institut, Südufer 10, 17493, Greifswald, Insel Riems, Germany.
Eugen BuehlerDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, 31 Center Drive, Bethesda, MD, 20892, USA.
Cynthia MartellaroLaboratory of Virology, Division of Intramural Research, National Institute for Allergy and Infectious Diseases, National Institutes of Health, 903 S 4th St., Hamilton, MT, 59840, USA.
Janine BrandtInstitute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Südufer 10, 17493, Greifswald, Insel Riems, Germany.
Lisa WendtInstitute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Südufer 10, 17493, Greifswald, Insel Riems, Germany.
Andreas MüllerInstitute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Südufer 10, 17493, Greifswald, Insel Riems, Germany.
Stephanie PeitschInstitute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Südufer 10, 17493, Greifswald, Insel Riems, Germany.
Sonja M BestLaboratory of Virology, Division of Intramural Research, National Institute for Allergy and Infectious Diseases, National Institutes of Health, 903 S 4th St., Hamilton, MT, 59840, USA.
Jürgen StechInstitute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Südufer 10, 17493, Greifswald, Insel Riems, Germany.
Stefan FinkeInstitute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Südufer 10, 17493, Greifswald, Insel Riems, Germany.
Angela Römer-OberdörferInstitute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Südufer 10, 17493, Greifswald, Insel Riems, Germany.
Allison GrosethLaboratory of Virology, Division of Intramural Research, National Institute for Allergy and Infectious Diseases, National Institutes of Health, 903 S 4th St., Hamilton, MT, 59840, USA.
Heinz FeldmannLaboratory of Virology, Division of Intramural Research, National Institute for Allergy and Infectious Diseases, National Institutes of Health, 903 S 4th St., Hamilton, MT, 59840, USA.
Thomas HoenenLaboratory of Virology, Division of Intramural Research, National Institute for Allergy and Infectious Diseases, National Institutes of Health, 903 S 4th St., Hamilton, MT, 59840, USA. thomas.hoenen@fli.de.ORCID 0000-0002-5829-6305
National Institutes of Health · USFriedrich-Loeffler-Institut · DE

Funding

Viral Hemorrhagic Fevers: Disease Modeling and TransmissionZIAAI001089 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI FELDMANN, HEINRICH · 2009 to 2025
$50.7M
Virus-Host Interactions: Induction and Evasion of Host Innate ImmunityZIAAI001125 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI BEST, SONJA · 2010 to 2025
$28.1M
Deutsche Forschungsgemeinschaft HO 4155/4-1National Institute of Allergy and Infectious Diseases Intramural Research Program
6 · The paper itself

Abstract

backgroundThe 2014-2016 Ebola virus (EBOV) outbreak in West Africa highlighted the need for improved therapeutic options against this virus. Approaches targeting host factors/pathways essential for the virus are advantageous because they can potentially target a wide range of viruses, including newly emerging ones and because the development of resistance is less likely than when targeting the virus directly. However, systematic approaches for screening host factors important for EBOV have been hampered by the necessity to work with this virus at biosafety level 4 (BSL4).

methodsIn order to identify host factors involved in the EBOV life cycle, we performed a genome-wide siRNA screen comprising 64,755 individual siRNAs against 21,566 human genes to assess their activity in EBOV genome replication and transcription. As a screening platform, we used reverse genetics-based life cycle modelling systems that recapitulate these processes without the need for a BSL4 laboratory.

resultsAmong others, we identified the de novo pyrimidine synthesis pathway as an essential host pathway for EBOV genome replication and transcription, and confirmed this using infectious EBOV under BSL4 conditions. An FDA-approved drug targeting this pathway showed antiviral activity against infectious EBOV, as well as other non-segmented negative-sense RNA viruses.

conclusionsThis study provides a minable data set for every human gene regarding its role in EBOV genome replication and transcription, shows that an FDA-approved drug targeting one of the identified pathways is highly efficacious in vitro, and demonstrates the power of life cycle modelling systems for conducting genome-wide host factor screens for BSL4 viruses.

Indexed as

Genome, HumanVirus ReplicationAnimalsAntiviral AgentsCell Line, TumorChlorocebus aethiopsCloning, MolecularEbolavirusGene Knockdown TechniquesHEK293 CellsHost-Pathogen InteractionsHumansVero CellsAntiviral AgentsCarbamoyl phosphate synthetase 2 aspartate transcarbamylase and dihydroorotaseDe novo pyrimidine synthesisDihydroorotate dehydrogenaseEbola virusHost factorNNSVNon-segmented negative-sense RNA virusessiRNA screenTeriflunomide

Identifiers

PMID30081931
PMCPMC6090742
OpenAlexW2884282327

What OpenQuestion holds

Textmetadata
LicenceCC BY
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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.