ArticleJournal of virology2011
Inhibition of dengue virus by targeting viral NS4B protein.
Article in Journal of virology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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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.
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Who cites it
89 citing papers in PubMed, 164 citations in OpenAlex.
- 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
- Pathogenicity and virulence of Kyasanur Forest disease: A comprehensive review of an expanding zoonotic threat in southwestern India.Virulence · 2025Review
- Discovery of a potent anti-Zika virus benzamide series targeting the viral protein NS4B.bioRxiv : the preprint server for biology · 2025Article
- Development of a Noninfectious Japanese Encephalitis Virus Replicon for Antiviral Drug Screening and Gene Function Studies.Viruses · 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
- A zebrafish-based in vivo model of Zika virus infection unveils alterations of the glutamatergic neuronal development and NS4A as a key viral determinant of neuropathogenesis.PLoS pathogens · 2024Article
- 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
- The endoplasmic reticulum (ER): a crucial cellular hub in flavivirus infection and potential target site for antiviral interventions.Npj viruses · 2024Review
- Dengue virus pathogenesis and host molecular machineries.Journal of biomedical science · 2024Review
- 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
- Identification of an Arylnaphthalene Lignan Derivative as an Inhibitor against Dengue Virus Serotypes 1 to 4 (DENV-1 to -4) Using a Newly Developed DENV-3 Infectious Clone and Replicon.Microbiology spectrum · 2023Article
- Advances in viral encephalitis: Viral transmission, host immunity, and experimental animal models.Zoological research · 2023Review
- Flavivirus nonstructural proteins and replication complexes as antiviral drug targets.Current opinion in virology · 2023Review
- Review
29 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We report a novel inhibitor that selectively suppresses dengue virus (DENV) by targeting viral NS4B protein. The inhibitor was identified by screening a 1.8-million-compound library using a luciferase replicon of DENV serotype 2 (DENV-2). The compound specifically inhibits all four serotypes of DENV (50% effective concentration [EC(50)], 1 to 4 μM; and 50% cytotoxic concentration [CC(50)], >40 μM), but it does not inhibit closely related flaviviruses (West Nile virus and yellow fever virus) or nonflaviviruses (Western equine encephalomyelitis virus, Chikungunya virus, and vesicular stomatitis virus). A mode-of-action study suggested that the compound inhibits viral RNA synthesis. Replicons resistant to the inhibitor were selected in cell culture. Sequencing of the resistant replicons revealed two mutations (P104L and A119T) in the viral NS4B protein. Genetic analysis, using DENV-2 replicon and recombinant viruses, demonstrated that each of the two NS4B mutations alone confers partial resistance and double mutations confer additive resistance to the inhibitor in mammalian cells. In addition, we found that a replication defect caused by a lethal NS4B mutation could be partially rescued through trans complementation. The ability to complement NS4B in trans affected drug sensitivity when a single cell was coinfected with drug-sensitive and drug-resistant viruses. Mechanistically, NS4B was previously shown to interact with the viral NS3 helicase domain; one of the two NS4B mutations recovered in our resistance analysis-P104L-abolished the NS3-NS4B interaction (I. Umareddy, A. Chao, A. Sampath, F. Gu, and S. G. Vasudevan, J. Gen. Virol. 87:2605-2614, 2006). Collectively, the results suggest that the identified inhibitor targets the DENV NS4B protein, leading to a defect in viral RNA synthesis.
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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.