ArticleNature communications2024
Pan-serotype dengue virus inhibitor JNJ-A07 targets NS4A-2K-NS4B interaction with NS2B/NS3 and blocks replication organelle formation.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- Daily Mosnodenvir as Dengue Prophylaxis in a Controlled Human Infection Model.The New England journal of medicine · 2025Trial
- Dengue and aging: challenges and opportunities in prevention and care. A narrative review.Emerging microbes & infections · 2026Review
- Oral lipid prodrug V2043 (1-Antimicrobial agents and chemotherapy · 2026Article
- Review
- Viral Dynamic Model-Informed Dose Selection of Mosnodenvir Prophylaxis against DENV-3 in a Controlled Human Infection Model.Clinical pharmacology and therapeutics · 2026Article
- Cross-Family Mechanistic Analysis of Plant Alkaloids Against Neglected Arboviruses and Related RNA Viruses.Molecules (Basel, Switzerland) · 2026Review
- Computational discovery of DENV-3 RdRp allosteric inhibitors: biological evaluation and mechanistic studies.Molecular diversity · 2026Article
- In Vitro Antiviral Potential ofBiomedicines · 2026Article
- An orthoflavivirus inhibitor targeting multifunctional NS2A protein, a previously unidentified target.PLoS pathogens · 2026Article
- Discovery of a potent anti-Zika virus benzamide series targeting the viral protein NS4B.PLoS pathogens · 2026Article
- A genus-wide interaction atlas across NS4B orthologues identifies a conserved role for UFMylation in orthoflavivirus replication.Nature communications · 2026Article
- Zika NS2B Protein: In Vitro Formation of Large Multimeric Networks.International journal of molecular sciences · 2026Article
- Cryo-electron tomography reveals coupled flavivirus replication, budding and maturation.Nature communications · 2026Article
- In vitro synthesis of active recombinant orthoflavivirus nonstructural polyproteins in detergent micelles for biochemical analysis.Npj viruses · 2026Article
- Chlorinated bis-4-hydroxycoumarins suppress flavivirus replication by inhibiting dengue virus type 2 translation and replication.Scientific reports · 2026Article
- Affinity-based protein profiling of the antiviral natural product nanchangmycin.RSC chemical biology · 2026Article
- Application of Orthoflavivirus Pseudovirus Technology in Antiviral Research.International journal of molecular sciences · 2026Review
- Integrative proteome-wide structural analysis and high-throughput docking identify broad-spectrum antiviral scaffolds against Zika, Yellow Fever, West Nile, Saint Louis encephalitis, and Usutu viruses.Frontiers in cellular and infection microbiology · 2026Article
- Targeting dengue through mucosal vaccination: the potential of NS1 and bacterial spore-based delivery platforms.Frontiers in immunology · 2026Review
- Research progress of dengue virus T cell epitope mediated cellular immunity in avoiding ADE.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
Dengue fever represents a significant medical and socio-economic burden in (sub)tropical regions, yet antivirals for treatment or prophylaxis are lacking. JNJ-A07 was described as highly active against the different genotypes within each serotype of the disease-causing dengue virus (DENV). Based on clustering of resistance mutations it has been assumed to target DENV non-structural protein 4B (NS4B). Using a photoaffinity labeling compound with high structural similarity to JNJ-A07, here we demonstrate binding to NS4B and its precursor NS4A-2K-NS4B. Consistently, we report recruitment of the compound to intracellular sites enriched for these proteins. We further specify the mechanism-of-action of JNJ-A07, which has virtually no effect on viral polyprotein cleavage, but targets the interaction between the NS2B/NS3 protease/helicase complex and the NS4A-2K-NS4B cleavage intermediate. This interaction is functionally linked to de novo formation of vesicle packets (VPs), the sites of DENV RNA replication. JNJ-A07 blocks VPs biogenesis with little effect on established ones. A similar mechanism-of-action was found for another NS4B inhibitor, NITD-688. In summary, we unravel the antiviral mechanism of these NS4B-targeting molecules and show how DENV employs a short-lived cleavage intermediate to carry out an early step of the viral life cycle.
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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.