ArticlePLoS pathogens2015
Characterization of a Novel Human-Specific STING Agonist that Elicits Antiviral Activity Against Emerging Alphaviruses.
Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 118 citations in OpenAlex.
- STING: An Attractive Target for Autoimmune and Inflammatory Diseases.Medicinal research reviews · 2026Review
- Characterization of a transmembrane-activating STING agonist using genetically humanized mice.Cell reports · 2026Article
- STING agonists as antiviral agents.FEBS letters · 2026Review
- Article
- Activation of stimulator of interferon genes (STING) and inhibition of vascular endothelial growth factor receptor (VEGFR) by telatinib induce antitumor activity.The Journal of biological chemistry · 2026Article
- Innate immune sensing of alphavirus chikungunya: balancing antiviral defense and pathogenesis.Frontiers in immunology · 2026Review
- Comparative molecular, innate, and adaptive impacts of chemically diverse STING agonists.Vaccine · 2025Review
- Conjugated STING agonists.Molecular therapy. Nucleic acids · 2025Review
- Progress Update on STING Agonists as Vaccine Adjuvants.Vaccines · 2025Review
- Advances in antiviral strategies targeting mosquito-borne viruses: cellular, viral, and immune-related approaches.Virology journal · 2025Review
- Zebularine showed anti-tumor efficacy in clear cell renal cell carcinoma.Frontiers in pharmacology · 2025Article
- Design, synthesis, and STING-agonistic activity of benzo[b]thiophene-2-carboxamide derivatives.Molecular diversity · 2024Article
- Fangchinoline induces antiviral response by suppressing STING degradation.Journal of pharmaceutical analysis · 2024Article
- The cytosolic DNA-sensing cGAS-STING pathway in neurodegenerative diseases.CNS neuroscience & therapeutics · 2024Review
- Microtubule disruption synergizes with STING signaling to show potent and broad-spectrum antiviral activity.PLoS pathogens · 2024Article
- Review
- Biomaterial-enabled therapeutic modulation of cGAS-STING signaling for enhancing antitumor immunity.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- The Many Ways to Deal with STING.International journal of molecular sciences · 2023Review
- Innate immune pathway modulator screen identifies STING pathway activation as a strategy to inhibit multiple families of arbo and respiratory viruses.Cell reports. Medicine · 2023Article
- Unlocking STING as a Therapeutic Antiviral Strategy.International journal of molecular sciences · 2023Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
Pharmacologic stimulation of innate immune processes represents an attractive strategy to achieve multiple therapeutic outcomes including inhibition of virus replication, boosting antitumor immunity, and enhancing vaccine immunogenicity. In light of this we sought to identify small molecules capable of activating the type I interferon (IFN) response by way of the transcription factor IFN regulatory factor 3 (IRF3). A high throughput in vitro screen yielded 4-(2-chloro-6-fluorobenzyl)-N-(furan-2-ylmethyl)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carboxamide (referred to herein as G10), which was found to trigger IRF3/IFN-associated transcription in human fibroblasts. Further examination of the cellular response to this molecule revealed expression of multiple IRF3-dependent antiviral effector genes as well as type I and III IFN subtypes. This led to the establishment of a cellular state that prevented replication of emerging Alphavirus species including Chikungunya virus, Venezuelan Equine Encephalitis virus, and Sindbis virus. To define cellular proteins essential to elicitation of the antiviral activity by the compound we employed a reverse genetics approach that utilized genome editing via CRISPR/Cas9 technology. This allowed the identification of IRF3, the IRF3-activating adaptor molecule STING, and the IFN-associated transcription factor STAT1 as required for observed gene induction and antiviral effects. Biochemical analysis indicates that G10 does not bind to STING directly, however. Thus the compound may represent the first synthetic small molecule characterized as an indirect activator of human STING-dependent phenotypes. In vivo stimulation of STING-dependent activity by an unrelated small molecule in a mouse model of Chikungunya virus infection blocked viremia demonstrating that pharmacologic activation of this signaling pathway may represent a feasible strategy for combating emerging Alphaviruses.
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Registered trials
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.