ArticleJournal of virology2015
Discovery of Dengue Virus NS4B Inhibitors.
Article in Journal of virology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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.
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
39 citing papers in PubMed.
- 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
- Mechanistic insights into dengue virus inhibition by a clinical trial compound NITD-688.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Advances in antiviral strategies targeting mosquito-borne viruses: cellular, viral, and immune-related approaches.Virology journal · 2025Review
- Flavivirus NS4B proteins do not form homodimers: discrepancies with an AlphaFold-based oligomeric model.Computational and structural biotechnology journal · 2025Article
- Dengue virus: pathogenesis and potential for small molecule inhibitors.Bioscience reports · 2024Review
- Dengue virus pathogenesis and host molecular machineries.Journal of biomedical science · 2024Review
- Cascaded signal amplification strategy for ultra-specific, ultra-sensitive, and visual detection of Shigella flexneri.Mikrochimica acta · 2024Article
- Development in the Inhibition of Dengue Proteases as Drug Targets.Current medicinal chemistry · 2024Review
- Modelling the impact of JNJ-1802, a first-in-class dengue inhibitor blocking the NS3-NS4B interaction, on in-vitro DENV-2 dynamics.PLoS computational biology · 2023Article
- Flavivirus nonstructural proteins and replication complexes as antiviral drug targets.Current opinion in virology · 2023Review
- Review
- Article
- Targeted protein degradation as an antiviral approach.Antiviral research · 2023Article
- Flavivirus NS4B protein: Structure, function, and antiviral discovery.Antiviral research · 2022Review
- Review
- Advances in Computational Methods to Discover New NS2B-NS3 Inhibitors Useful Against Dengue and Zika Viruses.Current topics in medicinal chemistry · 2022Review
- A yellow fever virus NS4B inhibitor not only suppresses viral replication, but also enhances the virus activation of RIG-I-like receptor-mediated innate immune response.PLoS pathogens · 2022Article
- Dengue virus NS4B protein as a target for developing antivirals.Frontiers in cellular and infection microbiology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The four serotypes of dengue virus (DENV-1 to -4) represent the most prevalent mosquito-borne viral pathogens in humans. No clinically approved vaccine or antiviral is currently available for DENV. Here we report a spiropyrazolopyridone compound that potently inhibits DENV both in vitro and in vivo. The inhibitor was identified through screening of a 1.8-million-compound library by using a DENV-2 replicon assay. The compound selectively inhibits DENV-2 and -3 (50% effective concentration [EC50], 10 to 80 nM) but not DENV-1 and -4 (EC50,>20 M). Resistance analysis showed that a mutation at amino acid 63 of DENV-2 NS4B (a nonenzymatic transmembrane protein and a component of the viral replication complex) could confer resistance to compound inhibition. Genetic studies demonstrate that variations at amino acid 63 of viral NS4B are responsible for the selective inhibition of DENV-2 and -3. Medicinal chemistry improved the physicochemical properties of the initial “hit” (compound 1), leading to compound 14a, which has good in vivo pharmacokinetics. Treatment of DENV-2-infected AG129 mice with compound 14a suppressed viremia, even when the treatment started after viral infection. The results have proven the concept that inhibitors of NS4B could potentially be developed for clinical treatment of DENV infection. Compound 14a represents a potential preclinical candidate for treatment of DENV-2- and -3-infected patients.
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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.