ArticleJournal of virology2014
Activation of peripheral blood mononuclear cells by dengue virus infection depotentiates balapiravir.
Article in Journal of virology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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
37 citing papers in PubMed, 82 citations in OpenAlex.
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- Evaluating antiviral candidates for dengue virus infection: A review.Parasite epidemiology and control · 2026Review
- NS5-targeting nucleoside analogs inhibit dengue virus and other flaviviruses.PLoS pathogens · 2026Article
- Prodrug strategies in developing antiviral nucleoside analogs.RSC medicinal chemistry · 2026Review
- Dengue and severe dengue.Clinical microbiology reviews · 2025Review
- Discovery of a Novel Non-Nucleoside Inhibitor of RNA-Dependent RNA Polymerase Against Dengue Virus.MedComm · 2025Article
- Antiviral agents for dengue virus.Virologica Sinica · 2025Review
- Exploration of 4'-fluoro fleximer nucleoside analogues as potential broad-spectrum antiviral agents.Bioorganic & medicinal chemistry · 2025Article
- Dengue encephalitis: what's new?Current opinion in infectious diseases · 2025Review
- A Comprehensive Review of the Development and Therapeutic Use of Antivirals in Flavivirus Infection.Viruses · 2025Review
- Exploring plant-based dengue therapeutics: from laboratory to clinic.Tropical diseases, travel medicine and vaccines · 2024Article
- Dengue virus: pathogenesis and potential for small molecule inhibitors.Bioscience reports · 2024Review
- Article
- Computational Advancement towards the Identification of Natural Inhibitors for Dengue Virus: A Brief Review.Combinatorial chemistry & high throughput screening · 2024Review
- Vector-Transmitted Flaviviruses: An Antiviral Molecules Overview.Microorganisms · 2023Review
- Review
- Finding a chink in the armor: Update, limitations, and challenges toward successful antivirals against flaviviruses.PLoS neglected tropical diseases · 2022Review
- Phytochemical Compound Screening to Identify Novel Small Molecules against Dengue Virus: A Docking and Dynamics Study.Molecules (Basel, Switzerland) · 2022Article
- Evaluation of AT-752, a Double Prodrug of a Guanosine Nucleotide Analog withAntimicrobial agents and chemotherapy · 2021Article
- Current Trends and Limitations in Dengue Antiviral Research.Tropical medicine and infectious disease · 2021Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In a recent clinical trial, balapiravir, a prodrug of a cytidine analog (R1479), failed to achieve efficacy (reducing viremia after treatment) in dengue patients, although the plasma trough concentration of R1479 remained above the 50% effective concentration (EC(50)). Here, we report experimental evidence to explain the discrepancy between the in vitro and in vivo results and its implication for drug development. R1479 lost its potency by 125-fold when balapiravir was used to treat primary human peripheral blood mononuclear cells (PBMCs; one of the major cells targeted for viral replication) that were preinfected with dengue virus. The elevated EC(50) was greater than the plasma trough concentration of R1479 observed in dengue patients treated with balapiravir and could possibly explain the efficacy failure. Mechanistically, dengue virus infection triggered PBMCs to generate cytokines, which decreased their efficiency of conversion of R1479 to its triphosphate form (the active antiviral ingredient), resulting in decreased antiviral potency. In contrast to the cytidine-based compound R1479, the potency of an adenosine-based inhibitor of dengue virus (NITD008) was much less affected. Taken together, our results demonstrate that viral infection in patients before treatment could significantly affect the conversion of the prodrug to its active form; such an effect should be calculated when estimating the dose efficacious for humans.
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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.