ArticlePLoS neglected tropical diseases2019
Discovery of a small molecule inhibitor targeting dengue virus NS5 RNA-dependent RNA polymerase.
Article in PLoS neglected tropical diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 89 citations in OpenAlex.
- Marine-Derived Natural Products Against Flaviviruses: Mechanisms, Evidence, and Future Directions.Marine drugs · 2026Review
- Antibody-Dependent Enhancement in Flavivirus Infections: From Fc Receptor Signaling to Vaccine and Therapeutic Design.Viruses · 2026Review
- Computational discovery of DENV-3 RdRp allosteric inhibitors: biological evaluation and mechanistic studies.Molecular diversity · 2026Article
- Identification of potential inhibitors of dengue virus ns5 methyltransferase and polymerase domains through virtual screening and molecular dynamics studies.Journal of molecular modeling · 2026Article
- Dengue Virus NS5 Target Discovery: A Comprehensive in Silico Exploration of Novel Druggable Sites for Pan-Serotype Antiviral Design.International journal of molecular sciences · 2026Article
- Chlorinated bis-4-hydroxycoumarins suppress flavivirus replication by inhibiting dengue virus type 2 translation and replication.Scientific reports · 2026Article
- Interplay between innate immune cells and inflammatory mediators in dengue infection: an evolving therapeutic paradigm.Expert reviews in molecular medicine · 2025Review
- Crystallographic Fragment Screening of the Dengue Virus Polymerase Reveals Multiple Binding Sites for the Development of Non-nucleoside Antiflavivirals.Journal of medicinal chemistry · 2025Article
- Comparative analysis of phytocompounds and repurposed drugs against dengue virus serotypes employing an in silico study.Scientific reports · 2025Article
- Identification of Potential Inhibitors Targeting Non-Structural Proteins NS3 and NS5 of Dengue Virus Using Docking and Deep Learning Approaches.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Dengue Virus Inhibitors as Potential Broad-Spectrum Flavivirus Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Identification of Benzothiophene-Derived Inhibitors of Flaviviruses by Targeting RNA-Dependent RNA Polymerase.Viruses · 2025Article
- i-DENV: development of QSAR based regression models for predicting inhibitors targeting non-structural (NS) proteins of dengue virus.Frontiers in pharmacology · 2025Article
- Dengue virus: pathogenesis and potential for small molecule inhibitors.Bioscience reports · 2024Review
- A jingmenvirus RNA-dependent RNA polymerase structurally resembles the flavivirus counterpart but with different features at the initiation phase.Nucleic acids research · 2024Article
- Genetic regions affecting the replication and pathogenicity of dengue virus type 2.PLoS neglected tropical diseases · 2024Article
- Article
- Harnessing Natural Resources for Advancements in Dengue Virus Treatment.Current topics in medicinal chemistry · 2024Review
- Galidesivir Triphosphate Promotes Stalling of Dengue-2 Virus Polymerase Immediately Prior to Incorporation.ACS infectious diseases · 2023Article
- Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dengue is a mosquito-borne viral infection that has spread globally in recent years. Around half of the world's population, especially in the tropics and subtropics, is at risk of infection. Every year, 50-100 million clinical cases are reported, and more than 500,000 patients develop the symptoms of severe dengue infection: dengue haemorrhagic fever and dengue shock syndrome, which threaten life in Asia and Latin America. No antiviral drug for dengue is available. The dengue virus (DENV) non-structural protein 5 (NS5), which possesses the RNA-dependent RNA polymerase (RdRp) activity and is responsible for viral replication and transcription, is an attractive target for anti-dengue drug development. In the present study, 16,240 small-molecule compounds in a fragment library were screened for their capabilities to inhibit the DENV type 2 (DENV2) RdRp activities in vitro. Based on in cellulo antiviral and cytotoxity assays, we selected the compound RK-0404678 with the EC50 value of 6.0 μM for DENV2. Crystallographic analyses revealed two unique binding sites for RK-0404678 within the RdRp, which are conserved in flavivirus NS5 proteins. No resistant viruses emerged after nine rounds of serial passage of DENV2 in the presence of RK-0404678, suggesting the high genetic barrier of this compound to the emergence of a resistant virus. Collectively, RK-0404678 and its binding sites provide a new framework for antiviral drug development.
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