Evidence map›Paper›PMID 28982551›Full record

ArticleAntiviral research2017

A cell-based high throughput screening assay for the discovery of cGAS-STING pathway agonists.

Bowei Liu, Liudi Tang, Xiaohui Zhang, Julia Ma, Mohit Sehgal, Junjun Cheng, Xuexiang Zhang, Yan Zhou, Yanming Du, John Kulp and 2 more

Open access · greenAbstract read
In one paragraph

Article in Antiviral research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

34 citing papers in PubMed, 66 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Conjugated STING agonists.Molecular therapy. Nucleic acids · 2025
    Review
  5. Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Review
  12. Significance of the cGAS-STING Pathway in Health and Disease.International journal of molecular sciences · 2023
    Review
  13. Review
  14. Biomaterial-enabled therapeutic modulation of cGAS-STING signaling for enhancing antitumor immunity.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
    Review
  15. Unlocking STING as a Therapeutic Antiviral Strategy.International journal of molecular sciences · 2023
    Review
  16. Mn-based cGAS-STING activation for tumor therapy.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2023
    Article
  17. Article
  18. Review
  19. Review
  20. Review
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

12 authors at 5 institutions in 2 countries.

Bowei LiuBaruch S. Blumberg Institute, Hepatitis B Foundation, Doylestown, PA, USA; Department of Gastroenterology, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou, Henan, China.
Liudi TangMicrobiology and Immunology Graduate Program, Drexel University College of Medicine, Philadelphia, PA, USA.
Xiaohui ZhangBaruch S. Blumberg Institute, Hepatitis B Foundation, Doylestown, PA, USA; Artificial Liver Center, Beijing You'an Hospital, Capital Medical University, Beijing, China.
Julia MaBaruch S. Blumberg Institute, Hepatitis B Foundation, Doylestown, PA, USA.
Mohit SehgalBaruch S. Blumberg Institute, Hepatitis B Foundation, Doylestown, PA, USA.
Junjun ChengBaruch S. Blumberg Institute, Hepatitis B Foundation, Doylestown, PA, USA.
Xuexiang ZhangBaruch S. Blumberg Institute, Hepatitis B Foundation, Doylestown, PA, USA.
Yan ZhouBiostatistics and Bioinformatics Facility, Fox Chase Cancer Center, Philadelphia, PA, USA.
Yanming DuBaruch S. Blumberg Institute, Hepatitis B Foundation, Doylestown, PA, USA.
John KulpBaruch S. Blumberg Institute, Hepatitis B Foundation, Doylestown, PA, USA.
Ju-Tao GuoBaruch S. Blumberg Institute, Hepatitis B Foundation, Doylestown, PA, USA. Electronic address: ju-tao.guo@bblumberg.org.
Jinhong ChangBaruch S. Blumberg Institute, Hepatitis B Foundation, Doylestown, PA, USA. Electronic address: jinhong.chang@bblumberg.org.
Hepatitis B Foundation · USCapital Medical University · CNDrexel University · USFox Chase Cancer Center · USZhengzhou University · CN

Funding

Evaulation of therapeutic benefits of HBV nucleocapsid assembly inhibitorsR01AI113267 · NIAID · DREXEL UNIVERSITY · PI DU, YANMING, GUO, JU-TAO · 2014 to 2018
$2.9M
NIAID NIH HHS R01 AI113267
6 · The paper itself

Abstract

Stimulator of interferon genes (STING) is an endoplasmic reticulum transmembrane protein that serves as a molecular hub for activation of interferon and inflammatory cytokine response by multiple cellular DNA sensors. Not surprisingly, STING has been demonstrated to play an important role in host defense against microorganisms and pharmacologic activation of STING is considered as an attractive strategy to treat viral diseases and boost antitumor immunity. In light of this we established a HepAD38-derived reporter cell line that expresses firefly luciferase in response to the activation of cyclic GMP-AMP synthase (cGAS)-STING pathway for high throughput screening (HTS) of small molecular human STING agonists. This cell-based reporter assay required only 4 h treatment with a reference STING agonist to induce a robust luciferase signal and was demonstrated to have an excellent performance in HTS format. By screening 16,000 compounds, a dispiro diketopiperzine (DSDP) compound was identified to induce cytokine response in a manner dependent on the expression of functional human STING, but not mouse STING. Moreover, we showed that DSDP induced an interferon-dominant cytokine response in human skin fibroblasts and peripheral blood mononuclear cells, which in turn potently suppressed the replication of yellow fever virus, dengue virus and Zika virus. We have thus established a robust cell-based assay system suitable for rapid discovery and mechanistic analyses of cGAS-STING pathway agonists. Identification of DSDP as a human STING agonist enriches the pipelines of STING-targeting drug development for treatment of viral infections and cancers.

Indexed as

High-Throughput Screening AssaysAnimalsAntiviral AgentsCells, CulturedCell SurvivalCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseDrug DiscoveryFlavivirusGene ExpressionHumansImmunity, InnateInterferon InducersLethal Dose 50Membrane ProteinsMiceMutationAntiviral AgentscGAS protein, humanCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseInterferon InducersMembrane ProteinsNucleotidyltransferasesPiperazinesSpiro CompoundsSTING1 protein, humanSTING ProteinTranscription FactorsAntiviralHigh throughput assayInnate immuneSTING

Identifiers

PMID28982551
PMCPMC5789800
OpenAlexW2761906648

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.