Evidence map›Paper›PMID 26307636›Full record

ArticleBiochemistry2015

Replication-Competent Influenza Virus and Respiratory Syncytial Virus Luciferase Reporter Strains Engineered for Co-Infections Identify Antiviral Compounds in Combination Screens.

Dan Yan, Marco Weisshaar, Kristen Lamb, Hokyung K Chung, Michael Z Lin, Richard K Plemper

Abstract read
In one paragraph

Article in Biochemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
4.1field-weighted citation impact, top 6% 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

31 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
  2. Article
  3. Reporter-expressing viruses for antiviral drug discovery research.Frontiers in cellular and infection microbiology · 2025
    Review
  4. Review
  5. Article
  6. Article
  7. Treatment of Respiratory Viral Coinfections.Epidemiologia (Basel, Switzerland) · 2022
    Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
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  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

6 authors at 2 institutions in 1 country.

Dan YanInstitute for Biomedical Sciences, Georgia State University , Atlanta, Georgia 30303-3222, United States.
Marco WeisshaarInstitute for Biomedical Sciences, Georgia State University , Atlanta, Georgia 30303-3222, United States.
Kristen LambInstitute for Biomedical Sciences, Georgia State University , Atlanta, Georgia 30303-3222, United States.
Hokyung K ChungDepartment of Biology, Stanford University , Stanford, California 94305-5020, United States.
Michael Z LinDepartment of Bioengineering, Stanford University , Stanford, California 94305, United States.
Richard K PlemperInstitute for Biomedical Sciences, Georgia State University , Atlanta, Georgia 30303-3222, United States.
Georgia State University · USStanford University · US

Funding

TRAINING & OUTREACH COREP50GM107615 · NIGMS · STANFORD UNIVERSITY · PI SCOTT, MATTHEW P. · 2013 to 2017
$10.9M
Identification and Pre-Clinical Evaluation of Measles Virus InhibitorsR01AI071002 · NIAID · GEORGIA STATE UNIVERSITY · PI PLEMPER, RICHARD K. · 2006 to 2022
$6.6M
Novel Therapeutics against Respiratory Syncytial Virus InfectionR01HD079327 · NICHD · GEORGIA STATE UNIVERSITY · PI PLEMPER, RICHARD K. · 2014 to 2018
$2.8M
Identification and Hit-to-Lead Development of Influenza A Virus InhibitorsR21AI119196 · NIAID · GEORGIA STATE UNIVERSITY · PI PLEMPER, RICHARD K. · 2015 to 2016
$436k
NIAID NIH HHS AI071002NIAID NIH HHS AI119196NIAID NIH HHS R01 AI071002NIAID NIH HHS R21 AI119196NICHD NIH HHS HD079327NICHD NIH HHS R01 HD079327NIGMS NIH HHS P50 GM107615
6 · The paper itself

Abstract

Myxoviruses such as influenza A virus (IAV) and respiratory syncytial virus (RSV) are major human pathogens, mandating the development of novel therapeutics. To establish a high-throughput screening protocol for the simultaneous identification of pathogen- and host-targeted hit candidates against either pathogen or both, we have attempted co-infection of cells with IAV and RSV. However, viral replication kinetics were incompatible, RSV signal window was low, and an IAV-driven minireplicon reporter assay used in initial screens narrowed the host cell range and restricted the assay to single-cycle infections. To overcome these limitations, we developed an RSV strain carrying firefly luciferase fused to an innovative universal small-molecule assisted shut-off domain, which boosted assay signal window, and a hyperactive fusion protein that synchronized IAV and RSV reporter expression kinetics and suppressed the identification of RSV entry inhibitors sensitive to a recently reported RSV pan-resistance mechanism. Combined with a replication-competent recombinant IAV strain harboring nanoluciferase, the assay performed well on a human respiratory cell line and supports multicycle infections. Miniaturized to 384-well format, the protocol was validated through screening of a set of the National Institutes of Health Clinical Collection (NCC) in quadruplicate. These test screens demonstrated favorable assay parameters and reproducibility. Application to a LOPAC library of bioactive compounds in a proof-of-concept campaign detected licensed antimyxovirus therapeutics, ribavirin and the neuraminidase inhibitor zanamivir, and identified two unexpected RSV-specific hit candidates, Fenretinide and the opioid receptor antagonist BNTX-7. Hits were evaluated in direct and orthogonal dose-response counterscreens using a standard recRSV reporter strain expressing Renilla luciferase.

Indexed as

AnimalsAntiviral AgentsBenzylidene CompoundsCell LineCoinfectionDogsDose-Response Relationship, DrugFeasibility StudiesFenretinideGenes, ReporterHigh-Throughput Screening AssaysHumansInfluenza A virusLuciferases, FireflyLuciferases, RenillaNaltrexone7-benzylidenenaltrexoneAntiviral AgentsBenzylidene CompoundsFenretinideLuciferases, FireflyLuciferases, RenillaNaltrexoneNarcotic AntagonistsNeuraminidaseRibavirinZanamivir

Identifiers

PMID26307636
PMCPMC4719150
OpenAlexW1166101103

What OpenQuestion holds

Textmetadata
LicenceTDM
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.