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

Overview of attention for article published in Genome Medicine, August 2018
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (73rd percentile)

Mentioned by

twitter
9 tweeters
patent
1 patent

Citations

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31 Dimensions

Readers on

mendeley
46 Mendeley
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Title
A genome-wide siRNA screen identifies a druggable host pathway essential for the Ebola virus life cycle
Published in
Genome Medicine, August 2018
DOI 10.1186/s13073-018-0570-1
Pubmed ID
Authors

Scott Martin, Abhilash I. Chiramel, Marie Luisa Schmidt, Yu-Chi Chen, Nadia Whitt, Ari Watt, Eric C. Dunham, Kyle Shifflett, Shelby Traeger, Anne Leske, Eugen Buehler, Cynthia Martellaro, Janine Brandt, Lisa Wendt, Andreas Müller, Stephanie Peitsch, Sonja M. Best, Jürgen Stech, Stefan Finke, Angela Römer-Oberdörfer, Allison Groseth, Heinz Feldmann, Thomas Hoenen

Abstract

The 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). In 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. Among 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. This 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.

Twitter Demographics

The data shown below were collected from the profiles of 9 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 46 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 46 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 11 24%
Researcher 6 13%
Student > Bachelor 5 11%
Student > Master 5 11%
Other 3 7%
Other 5 11%
Unknown 11 24%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 12 26%
Medicine and Dentistry 9 20%
Agricultural and Biological Sciences 6 13%
Immunology and Microbiology 2 4%
Pharmacology, Toxicology and Pharmaceutical Science 1 2%
Other 4 9%
Unknown 12 26%

Attention Score in Context

This research output has an Altmetric Attention Score of 7. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 August 2021.
All research outputs
#3,652,878
of 20,334,212 outputs
Outputs from Genome Medicine
#746
of 1,317 outputs
Outputs of similar age
#74,359
of 296,534 outputs
Outputs of similar age from Genome Medicine
#1
of 1 outputs
Altmetric has tracked 20,334,212 research outputs across all sources so far. Compared to these this one has done well and is in the 81st percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,317 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 23.4. This one is in the 42nd percentile – i.e., 42% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 296,534 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 73% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them