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Related Experiment Video

Updated: Jun 15, 2025

High-throughput Screening for Broad-spectrum Chemical Inhibitors of RNA Viruses
11:34

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High throughput screening for SARS-CoV-2 helicase inhibitors.

Yuka Otsuka1, Eunjung Kim2, Austin Krueger2

  • 1The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Department of Molecular Medicine, Midwest AViDD HTS Core B, Jupiter, FL 33458, United States.

SLAS Discovery : Advancing Life Sciences R & D
|August 22, 2024
PubMed
Summary

Researchers screened over 650,000 compounds to find inhibitors for SARS-CoV-2 nsP13 helicase. This high-throughput screening identified 674 potential antiviral compounds targeting a key SARS-CoV-2 protein.

Keywords:
Biochemical assayCOVID-19HTSHelicasensP13

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Last Updated: Jun 15, 2025

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Area of Science:

  • Virology
  • Drug Discovery
  • Biochemistry

Background:

  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of deaths globally.
  • New antiviral drugs are crucial to combat emerging SARS-CoV-2 variants.
  • The National Institute of Allergy and Infectious Diseases (NIAID) established Antiviral Drug Discovery (AViDD) Centers to address pandemic threats.

Purpose of the Study:

  • To identify inhibitors of SARS-CoV-2 non-structural protein 13 (nsP13) as potential antiviral agents.
  • To develop and implement a high-throughput screening (HTS)-compatible assay for SARS-CoV-2 nsP13 helicase activity.

Main Methods:

  • Developed a 1,536-well plate assay to measure SARS-CoV-2 nsP13 helicase activity.
  • Screened a library of approximately 650,000 compounds.
  • Performed in-silico analysis, orthogonal assays, titration assays, and counterscreen assays to validate hits.

Main Results:

  • The primary screen yielded 7,009 hits with a Z' value of 0.86 ± 0.05.
  • 1,763 compounds were confirmed upon retesting.
  • 674 compounds showed consistent inhibition with IC50 <10 μM.

Conclusions:

  • The developed assay is suitable for HTS platforms to discover SARS-CoV-2 nsP13 inhibitors.
  • Identified 674 compounds warranting further investigation as potential SARS-CoV-2 antivirals.
  • These findings contribute to the development of novel antiviral therapies against SARS-CoV-2.