ArticleAntimicrobial agents and chemotherapy2014
A novel dengue virus inhibitor, BP13944, discovered by high-throughput screening with dengue virus replicon cells selects for resistance in the viral NS2B/NS3 protease.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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41 citing papers in PubMed, 88 citations in OpenAlex.
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- Construction of an infectious clone of novel duck picornavirus using the infectious subgenomic amplicon method.Scientific reports · 2025Article
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- Rapid Rescue of Goose Astrovirus Genome via Red/ET Assembly.Food and environmental virology · 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
- Development in the Inhibition of Dengue Proteases as Drug Targets.Current medicinal chemistry · 2024Review
- Exploring the Targets of Dengue Virus and Designs of Potential Inhibitors.Combinatorial chemistry & high throughput screening · 2024Article
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- A review on structural genomics approach applied for drug discovery against three vector-borne viral diseases: Dengue, Chikungunya and Zika.Virus genes · 2022Review
- A simple reverse genetics method to generate recombinant coronaviruses.EMBO reports · 2022Article
- Seawater fungi-derived compound screening to identify novel small molecules against dengue virus NS5 methyltransferase and NS2B/NS3 protease.Informatics in medicine unlocked · 2022Article
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- Optimization of 4-Anilinoquinolines as Dengue Virus Inhibitors.Molecules (Basel, Switzerland) · 2021Article
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- Current Trends and Limitations in Dengue Antiviral Research.Tropical medicine and infectious disease · 2021Review
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- Virtual Screening for Potential Inhibitors of Human Hexokinase II for the Development of Anti-Dengue Therapeutics.Biotech (Basel (Switzerland)) · 2020Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dengue virus (DENV) causes disease globally, resulting in an estimated 25 to 100 million new infections per year. No effective DENV vaccine is available, and the current treatment is only supportive. Thus, there is an urgent need to develop therapeutic agents to cure this epidemic disease. In the present study, we identified a potential small-molecule inhibitor, BP13944, via high-throughput screening (HTS) of 60,000 compounds using a stable cell line harboring an efficient luciferase replicon of DENV serotype 2 (DENV-2). BP13944 reduced the expression of the DENV replicon reporter in cells, showing a 50% effective concentration (EC50) of 1.03 ± 0.09 μM. Without detectable cytotoxicity, the compound inhibited replication or viral RNA synthesis in all four serotypes of DENV but not in Japanese encephalitis virus (JEV). Sequencing analyses of several individual clones derived from BP13944-resistant RNAs purified from cells harboring the DENV-2 replicon revealed a consensus amino acid substitution (E66G) in the region of the NS3 protease domain. Introduction of E66G into the DENV replicon, an infectious DENV cDNA clone, and recombinant NS2B/NS3 protease constructs conferred 15.2-, 17.2-, and 3.1-fold resistance to BP13944, respectively. Our results identify an effective small-molecule inhibitor, BP13944, which likely targets the DENV NS3 protease. BP13944 could be considered part of a more effective treatment regime for inhibiting DENV in the future.
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