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Updated: May 29, 2026

High-throughput Screening for Broad-spectrum Chemical Inhibitors of RNA Viruses
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Targeting dengue virus envelope protein: Insights from structural analysis and high-throughput screening.

Ruifang Wei1, Edgar Jacoby1, Emmanuel Gustin1

  • 1Johnson & Johnson, Turnhoutseweg 30, Beerse, 2340, Belgium.

Antiviral Research
|May 27, 2026
PubMed
Summary

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Researchers identified new ways to block dengue virus (DENV-2) entry into cells. They found three potential drug targets on the virus

Area of Science:

  • Virology
  • Structural Biology
  • Drug Discovery

Background:

  • Dengue virus (DENV) is a major global health concern, causing significant morbidity and mortality.
  • The DENV envelope (E) protein is crucial for viral entry into host cells by mediating membrane fusion.
  • Inhibiting E protein-mediated fusion presents a viable antiviral strategy.

Purpose of the Study:

  • To identify novel drug-binding sites on the DENV-2 E protein.
  • To discover small molecules that inhibit DENV-2 fusion and entry.
  • To establish a framework for flavivirus entry inhibitor development.

Main Methods:

  • Determined three-dimensional structures of DENV-2 soluble E protein (sE) in pre- and intermediate-fusion states.
  • Performed virtual screening of small molecule libraries against identified drug-binding regions.
Keywords:
DENV-2Druggable pocketsEnvelope (E) proteinFusion inhibitorsHigh-content imaging (HCI)High-throughput screening (HTS)Virtual screening

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Related Experiment Videos

Last Updated: May 29, 2026

High-throughput Screening for Broad-spectrum Chemical Inhibitors of RNA Viruses
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Published on: May 5, 2014

Assays for the Identification of Novel Antivirals against Bluetongue Virus
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Published on: October 11, 2013

High-throughput Antiviral Assays to Screen for Inhibitors of Zika Virus Replication
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High-throughput Antiviral Assays to Screen for Inhibitors of Zika Virus Replication

Published on: October 30, 2021

  • Utilized a high-content imaging (HCI)-based cell-cell fusion assay for high-throughput screening.
  • Validated hits using infection-based assays.

    • Main Results:

    • Identified three potential drug-binding regions on the DENV-2 sE: β-OG pocket, fusion-loop region, and stem-zipper-associated region.
    • Discovered several compounds with micromolar anti-fusion activity against DENV-2.
    • Narrowed down to three promising fusion inhibitors targeting the predicted sites.

    Conclusions:

    • The study provides a rational approach for discovering flavivirus entry inhibitors.
    • Identified specific structural regions and compounds for further development of dengue antivirals.
    • Highlights the potential of targeting viral fusion mechanisms for therapeutic intervention.