ArticlePLoS pathogens2013
Inhibition of pyrimidine biosynthesis pathway suppresses viral growth through innate immunity.
Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 166 citations in OpenAlex.
- Dihydropyrimidine dehydrogenase modulates immune response to checkpoint inhibition in mismatch repair deficient/microsatellite instability-high colorectal cancer.Journal for immunotherapy of cancer · 2026Article
- Lassa and Mopeia viruses produce different RIG-I-activating RNA in the absence of a functional viral exoribonuclease domain.Journal of virology · 2026Article
- Oncolytic virus hijacks GOT1 and pyrimidinosomes to fuel pyrimidine synthesis for replication in tumor cells.Tumour virus research · 2026Article
- Discovery of a potent anti-Zika virus benzamide series targeting the viral protein NS4B.PLoS pathogens · 2026Article
- A High-Throughput Antiviral Assay Based on a Sindbis Virus-GFP for the Discovery of Inhibitors of Alphavirus Replication.Viruses · 2026Article
- Antimycin A inhibits alpha-herpesvirus replication by disrupting the formation of pyrimidinosomes.Journal of advanced research · 2026Article
- Sjögren's disease metabolome reveals biomarker signatures to characterise patients and assess disease activity.RMD open · 2026Article
- SAMD9L inhibits flavivirus translation independently of its capacity to trigger innate immune response.PLoS pathogens · 2025Article
- Arzanol Inhibits Human Dihydroorotate Dehydrogenase and Shows Antiviral Activity.Journal of natural products · 2025Article
- Discovery of a potent anti-Zika virus benzamide series targeting the viral protein NS4B.bioRxiv : the preprint server for biology · 2025Article
- Viral Reprogramming of Nucleotide Synthesis and Its Impact on Viral Infection.Journal of medical virology · 2025Review
- MITD1 is a brain-specific interferon-inducible factor that inhibits flavivirus replication.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Fructose-1,6-diphosphate inhibits viral replication by promoting the lysosomal degradation of HMGB1 and blocking the binding of HMGB1 to the viral genome.PLoS pathogens · 2024Article
- The RBPome of influenza A virus NP-mRNA reveals a role for TDP-43 in viral replication.Nucleic acids research · 2024Article
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- The double life of a chemotherapy drug: Immunomodulatory functions of gemcitabine in cancer.Cancer medicine · 2024Review
- Modulation of nucleotide metabolism by picornaviruses.PLoS pathogens · 2024Article
- DHODH inhibition enhances the efficacy of immune checkpoint blockade by increasing cancer cell antigen presentation.bioRxiv : the preprint server for biology · 2024Article
- Progress of cGAS-STING signaling pathway-based modulation of immune response by traditional Chinese medicine in clinical diseases.Frontiers in immunology · 2024Review
- Review
33 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
16 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Searching for stimulators of the innate antiviral response is an appealing approach to develop novel therapeutics against viral infections. Here, we established a cell-based reporter assay to identify compounds stimulating expression of interferon-inducible antiviral genes. DD264 was selected out of 41,353 compounds for both its immuno-stimulatory and antiviral properties. While searching for its mode of action, we identified DD264 as an inhibitor of pyrimidine biosynthesis pathway. This metabolic pathway was recently identified as a prime target of broad-spectrum antiviral molecules, but our data unraveled a yet unsuspected link with innate immunity. Indeed, we showed that DD264 or brequinar, a well-known inhibitor of pyrimidine biosynthesis pathway, both enhanced the expression of antiviral genes in human cells. Furthermore, antiviral activity of DD264 or brequinar was found strictly dependent on cellular gene transcription, nuclear export machinery, and required IRF1 transcription factor. In conclusion, the antiviral property of pyrimidine biosynthesis inhibitors is not a direct consequence of pyrimidine deprivation on the virus machinery, but rather involves the induction of cellular immune response.
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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.