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Updated: Jun 15, 2025
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High-throughput Screening for Broad-spectrum Chemical Inhibitors of RNA Viruses
Published on: May 5, 2014
13.8K
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
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.
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.
