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Updated: Jun 17, 2026

High-throughput Screening for Broad-spectrum Chemical Inhibitors of RNA Viruses
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High-throughput screening identifies broad-spectrum Coronavirus entry inhibitors.

Suman Khan1, Efrat Ozer Partuk1, Jeanne Chiaravalli2

  • 1Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.

Iscience
|June 17, 2024
PubMed
Summary

Researchers screened over 200,000 molecules to find new antivirals. They identified novel small molecules and a derivative that show potential as broad-spectrum inhibitors against emerging coronaviruses (CoVs).

Keywords:
Health sciencesPharmacologyVirology

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Area of Science:

  • Virology
  • Drug Discovery
  • Molecular Biology

Background:

  • The COVID-19 pandemic underscored the urgent need for effective antivirals against emerging coronaviruses (CoVs).
  • Inhibiting the spike (S) glycoprotein-mediated viral entry presents a promising therapeutic strategy.
  • Targeting viral entry downstream of receptor binding is crucial for developing broad-spectrum antivirals.

Purpose of the Study:

  • To establish a high-throughput screening (HTS) platform for identifying small molecule inhibitors of coronavirus entry.
  • To screen a large library of small molecules for compounds that inhibit SARS-CoV-2 S glycoprotein-mediated viral entry.
  • To discover novel broad-spectrum antiviral agents effective against emerging coronaviruses.

Main Methods:

  • Development of a pseudovirus-based high-throughput screening (HTS) platform.
  • Screening of approximately 200,000 small molecules against SARS-CoV-2 S-bearing pseudoviruses.
  • Counter-screening and validation against MERS-CoV, SARS-CoV-2 variants (Alpha, Delta, Omicron), and authentic SARS-CoV-2.

Main Results:

  • Identified 65 SARS-CoV-2 S-specific inhibitors after counter-screening.
  • Five compounds, including Nafamostat, showed activity against MERS-CoV S-bearing pseudoviruses.
  • An unreported inhibitor and its derivative demonstrated potential as broad-spectrum antivirals against SARS-CoV-2 variants and authentic virus.

Conclusions:

  • The developed HTS platform is effective for identifying coronavirus entry inhibitors.
  • A novel inhibitor and its derivative show promise as broad-spectrum antivirals.
  • Further validation is warranted to explore the therapeutic potential of these compounds against emerging CoVs.