ArticleAntimicrobial agents and chemotherapy2016
Discovery of a Broad-Spectrum Antiviral Compound That Inhibits Pyrimidine Biosynthesis and Establishes a Type 1 Interferon-Independent Antiviral State.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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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.
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.
Who cites it
30 citing papers in PubMed, 58 citations in OpenAlex.
- Discovery of a potent anti-Zika virus benzamide series targeting the viral protein NS4B.PLoS pathogens · 2026Article
- 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
- Genetic and phenotypic changes to Venezuelan equine encephalitis virus following treatment with β-D-N4-hydroxycytidine, an RNA mutagen.Scientific reports · 2024Article
- The double life of a chemotherapy drug: Immunomodulatory functions of gemcitabine in cancer.Cancer medicine · 2024Review
- Gemcitabine Modulates HLA-I Regulation to Improve Tumor Antigen Presentation by Pancreatic Cancer Cells.International journal of molecular sciences · 2024Article
- Efficacy of a brain-penetrant antiviral in lethal Venezuelan and eastern equine encephalitis mouse models.Science translational medicine · 2023Article
- Inhibitors of Nucleotide Biosynthesis as Candidates for a Wide Spectrum of Antiviral Chemotherapy.Microorganisms · 2022Review
- Small Molecule Inhibitors Targeting Chikungunya Virus.Current topics in microbiology and immunology · 2022Review
- Search, Identification, and Design of Effective Antiviral Drugs Against Pandemic Human Coronaviruses.Advances in experimental medicine and biology · 2021Review
- Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2.Protein & cell · 2020Article
- Article
- Benzamidine ML336 inhibits plus and minus strand RNA synthesis of Venezuelan equine encephalitis virus without affecting host RNA production.Antiviral research · 2020Article
- All About the RNA: Interferon-Stimulated Genes That Interfere With Viral RNA Processes.Frontiers in immunology · 2020Review
- The ReFRAME library as a comprehensive drug repurposing library to identify mammarenavirus inhibitors.Antiviral research · 2019Article
- Therapeutic Advances Against ZIKV: A Quick Response, a Long Way to Go.Pharmaceuticals (Basel, Switzerland) · 2019Review
- Article
- Efficacy of a ML336 derivative against Venezuelan and eastern equine encephalitis viruses.Antiviral research · 2019Article
- Atovaquone Inhibits Arbovirus Replication through the Depletion of Intracellular Nucleotides.Journal of virology · 2019Article
- Untargeted metabolomics analysis of the upper respiratory tract of ferrets following influenza A virus infection and oseltamivir treatment.Metabolomics : Official journal of the Metabolomic Society · 2019Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Viral emergence and reemergence underscore the importance of developing efficacious, broad-spectrum antivirals. Here, we report the discovery of tetrahydrobenzothiazole-based compound 1, a novel, broad-spectrum antiviral lead that was optimized from a hit compound derived from a cytopathic effect (CPE)-based antiviral screen using Venezuelan equine encephalitis virus. Compound 1 showed antiviral activity against a broad range of RNA viruses, including alphaviruses, flaviviruses, influenza virus, and ebolavirus. Mechanism-of-action studies with metabolomics and molecular approaches revealed that the compound inhibits host pyrimidine synthesis and establishes an antiviral state by inducing a variety of interferon-stimulated genes (ISGs). Notably, the induction of the ISGs by compound 1 was independent of the production of type 1 interferons. The antiviral activity of compound 1 was cell type dependent with a robust effect observed in human cell lines and no observed antiviral effect in mouse cell lines. Herein, we disclose tetrahydrobenzothiazole compound 1 as a novel lead for the development of a broad-spectrum, antiviral therapeutic and as a molecular probe to study the mechanism of the induction of ISGs that are independent of type 1 interferons.
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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.