ArticleThe Journal of biological chemistry2015
The Role of Phosphodiesterase 12 (PDE12) as a Negative Regulator of the Innate Immune Response and the Discovery of Antiviral Inhibitors.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- Causal Association and Shared Genetics Between Asthma and COVID-19.Frontiers in immunology · 2022Pooled it
- Prevalence of Inflammatory Pathways Over Immuno-Tolerance in Peripheral Blood Mononuclear Cells of Recent-Onset Type 1 Diabetes.Frontiers in immunology · 2021Trial
- EEPD1 evolved a unique DNA clamping dimer protecting reversed replication forks.Nucleic acids research · 2026Article
- Molecular Responses to Temperature Changes Across Timescales in the Madagascar Ground Gecko (Paroedura picta).Molecular ecology · 2026Article
- Signature of Selection Analysis Reveals Candidate Genes Related to Climate Adaptation and Production Traits in Lao Native Goats.Journal of animal breeding and genetics = Zeitschrift fur Tierzuchtung und Zuchtungsbiologie · 2026Article
- Innate immune activation and mitochondrial ROS induce acute and persistent cardiac conduction system dysfunction after COVID-19.JCI insight · 2025Article
- Nuclear Fraction Proteome Analyses During rAAV Production of AAV2-Plasmid-Transfected HEK-293 Cells.International journal of molecular sciences · 2025Article
- PDE12 mediated pruning of the poly-A tail of mitochondrial DNA-encoded tRNAs is essential for survival.EMBO molecular medicine · 2025Article
- The potential therapeutic effect of phosphodiesterase 5 inhibitors in the acute ischemic stroke (AIS).Molecular and cellular biochemistry · 2024Review
- Non-coding RNAs expression in SARS-CoV-2 infection: pathogenesis, clinical significance, and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Advancements in Phosphodiesterase 5 Inhibitors: Unveiling Present and Future Perspectives.Pharmaceuticals (Basel, Switzerland) · 2023Review
- PDE12 in type 1 diabetes.Scientific reports · 2022Article
- How RNases Shape Mitochondrial Transcriptomes.International journal of molecular sciences · 2022Review
- The key features of SARS-CoV-2 leader and NSP1 required for viral escape of NSP1-mediated repression.RNA (New York, N.Y.) · 2022Article
- Article
- A genetic link between risk for Alzheimer's disease and severe COVID-19 outcomes via the OAS1 gene.Brain : a journal of neurology · 2021Article
- Utility of Bioluminescent Homogeneous Nucleotide Detection Assays in Measuring Activities of Nucleotide-Sugar Dependent Glycosyltransferases and Studying Their Inhibitors.Molecules (Basel, Switzerland) · 2021Article
- Article
- DNA-Encoded Chemical Libraries: A Comprehensive Review with Succesful Stories and Future Challenges.ACS pharmacology & translational science · 2021Review
- Hypotheses and facts for genetic factors related to severe COVID-19.World journal of virology · 2021Review
Corrections and comments
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Authors and funding
24 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
2',5'-Oligoadenylate synthetase (OAS) enzymes and RNase-L constitute a major effector arm of interferon (IFN)-mediated antiviral defense. OAS produces a unique oligonucleotide second messenger, 2',5'-oligoadenylate (2-5A), that binds and activates RNase-L. This pathway is down-regulated by virus- and host-encoded enzymes that degrade 2-5A. Phosphodiesterase 12 (PDE12) was the first cellular 2-5A- degrading enzyme to be purified and described at a molecular level. Inhibition of PDE12 may up-regulate the OAS/RNase-L pathway in response to viral infection resulting in increased resistance to a variety of viral pathogens. We generated a PDE12-null cell line, HeLaΔPDE12, using transcription activator-like effector nuclease-mediated gene inactivation. This cell line has increased 2-5A levels in response to IFN and poly(I-C), a double-stranded RNA mimic compared with the parental cell line. Moreover, HeLaΔPDE12 cells were resistant to viral pathogens, including encephalomyocarditis virus, human rhinovirus, and respiratory syncytial virus. Based on these results, we used DNA-encoded chemical library screening to identify starting points for inhibitor lead optimization. Compounds derived from this effort raise 2-5A levels and exhibit antiviral activity comparable with the effects observed with PDE12 gene inactivation. The crystal structure of PDE12 complexed with an inhibitor was solved providing insights into the structure-activity relationships of inhibitor potency and selectivity.
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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.