ArticleProceedings of the National Academy of Sciences of the United States of America2025
Mechanistic insights into dengue virus inhibition by a clinical trial compound NITD-688.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 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
11 citing papers in PubMed.
- Therapeutic approaches against dengue virus: current status of vaccines, antivirals, and monoclonal antibodies.Emerging microbes & infections · 2026Review
- Oral lipid prodrug V2043 (1-Antimicrobial agents and chemotherapy · 2026Article
- Conformational Dynamics of Viral Protease Precursors in Maturation, Inhibition, and Drug-Resistance Development.Viruses · 2026Review
- Nanoparticle vaccine formulations for dengue virus.RSC pharmaceutics · 2026Review
- The Flavivirus NS3 Protein: Its Multifaceted Roles and Therapeutic Potential.Journal of medical virology · 2026Review
- A genus-wide interaction atlas across NS4B orthologues identifies a conserved role for UFMylation in orthoflavivirus replication.Nature communications · 2026Article
- Antiviral Strategies Against Dengue Virus: Recent Insights into Compounds Targeting Viral and Host Factors.Current topics in microbiology and immunology · 2026Review
- A dual-reporter HCoV-OC43 for coronavirus biology and countermeasure development.Antiviral research · 2025Article
- Meeting report: 38th international conference on antiviral research in Las Vegas, United States of America, March 17-21, 2025.Antiviral research · 2025Article
- New dengue virus inhibitors targeting NS3-NS5 interaction identified byFrontiers in microbiology · 2025Article
- Structural elucidation of Langat virus helicase unveils dual-target inhibition for broad-spectrum anti-flaviviruses strategy.Frontiers in cellular and infection microbiology · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
15 authors.
Funding
Abstract
Dengue, caused by the dengue virus (DENV), presents a significant public health challenge with limited effective treatments. NITD-688 is a potent panserotype DENV inhibitor currently in Phase II clinical trials. However, its mechanism of action is not fully understood. Here, we present the molecular details of how NITD-688 inhibits DENV. NITD-688 binds directly to the nonstructural protein 4B (NS4B) with nanomolar affinities across all four DENV serotypes and specifically disrupts the interaction between NS4B and nonstructural protein 3 (NS3) without significantly changing the interactions between NS4B and other viral or host proteins. NS4B mutations that confer resistance to NITD-688 reduce both NITD-688 binding to NS4B and disruption of the NS4B/NS3 interaction. Specifically, NITD-688 blocks the interaction of NS3 with a cytosolic loop within NS4B. This inhibits the formation of new NS4B/NS3 complexes and disrupts preexisting complexes in vitro and DENV-infected cells, ultimately inhibiting viral replication. Consistent with this mechanism, NITD-688 retains greater potency in cellular assays with delayed treatment compared to JNJ-1802, another NS4B inhibitor that has been studied in Phase II clinical trials. Together, these findings provide critical insights into the mechanism of action of NITD-688, facilitating the development of novel flavivirus NS4B inhibitors and informing future clinical interventions against DENV.
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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.