Evidence map›Paper›PMID 28096399›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2017

Antiviral screening identifies adenosine analogs targeting the endogenous dsRNA Leishmania RNA virus 1 (LRV1) pathogenicity factor.

F Matthew Kuhlmann, John I Robinson, Gregory R Bluemling, Catherine Ronet, Nicolas Fasel, Stephen M Beverley

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
3.0field-weighted citation impact, top 9% 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

26 citing papers in PubMed, 46 citations in OpenAlex.

  1. Review
  2. Journal of parasitology research · 2026
    Review
  3. Article
  4. Analysis of Leishbuviridae from Trypanosomatids.Methods in molecular biology (Clifton, N.J.) · 2025
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Metabolic Pathways ofPharmaceutics · 2022
    Review
  13. Article
  14. Review
  15. Frontiers in cellular and infection microbiology · 2022
    Article
  16. Double-Stranded RNA Viruses Are Released FromFrontiers in microbiology · 2022
    Article
  17. Article
  18. Dissection of the macrophage response towards infection by theFrontiers in cellular and infection microbiology · 2022
    Article
  19. Article
  20. In and out:Frontiers in cellular and infection microbiology · 2022
    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

6 authors at 3 institutions in 2 countries.

F Matthew KuhlmannDepartment of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
John I RobinsonDepartment of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
Gregory R BluemlingEmory Institute for Drug Development, Emory University, Atlanta, GA 30329.
Catherine RonetDepartment of Biochemistry, University of Lausanne, 1066 Lausanne, Switzerland.
Nicolas FaselDepartment of Biochemistry, University of Lausanne, 1066 Lausanne, Switzerland.
Stephen M BeverleyDepartment of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110; stephen.beverley@wustl.edu.ORCID 0000-0001-5319-0811
Washington University in St. Louis · USUniversity of Lausanne · CHEmory University · US

Funding

MOLECULAR GENETICS OF LEISHMANIA USING DNA TRANSFECTIONR01AI029646 · NIAID · WASHINGTON UNIVERSITY · PI BEVERLEY, STEPHEN M · 1990 to 2015
$9.3M
Leishmania RNA virus (LRV) infectivity and host responsesR56AI099364 · NIAID · WASHINGTON UNIVERSITY · PI BEVERLEY, STEPHEN M · 2013 to 2013
$493k
NIAID NIH HHS R01 AI029646NIAID NIH HHS R56 AI099364
6 · The paper itself

Abstract

The endogenous double-stranded RNA (dsRNA) virus Leishmaniavirus (LRV1) has been implicated as a pathogenicity factor for leishmaniasis in rodent models and human disease, and associated with drug-treatment failures in Leishmania braziliensis and Leishmania guyanensis infections. Thus, methods targeting LRV1 could have therapeutic benefit. Here we screened a panel of antivirals for parasite and LRV1 inhibition, focusing on nucleoside analogs to capitalize on the highly active salvage pathways of Leishmania, which are purine auxotrophs. Applying a capsid flow cytometry assay, we identified two 2'-C-methyladenosine analogs showing selective inhibition of LRV1. Treatment resulted in loss of LRV1 with first-order kinetics, as expected for random virus segregation, and elimination within six cell doublings, consistent with a measured LRV1 copy number of about 15. Viral loss was specific to antiviral nucleoside treatment and not induced by growth inhibitors, in contrast to fungal dsRNA viruses. Comparisons of drug-treated LRV1

Indexed as

AnimalsAntiviral AgentsCapsid ProteinsLeishmania braziliensisLeishmania guyanensisLeishmaniasisLeishmaniavirusMice, Inbred C57BLNucleosidesNucleotidesAntiviral AgentsCapsid ProteinsNucleosidesNucleotideschemotherapyendobiont virustrypanosomatid protozoan parasiteviral segregationvirulence

Identifiers

PMID28096399
PMCPMC5293060
OpenAlexW2576831217

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.