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High-throughput Antiviral Assays to Screen for Inhibitors of Zika Virus Replication
Published on: October 30, 2021
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Small molecule inhibitor discovery for dengue virus protease using high-throughput screening
Mark Manzano1, Janak Padia, Radhakrishnan Padmanabhan
1Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Methods in Molecular Biology (Clifton, N.J.)
|April 4, 2014
Summary
Dengue virus (DENV) infections cause millions of cases yearly. Researchers developed a high-throughput screening assay to find inhibitors for the viral serine protease, a key target for new dengue antiviral drugs.
Area of Science:
- Virology
- Infectious Diseases
- Drug Discovery
Background:
- Dengue virus (DENV) is a significant global pathogen, causing over 300 million infections annually.
- While most infections are mild, severe dengue hemorrhagic fever/dengue shock syndrome affects 500,000 cases, leading to 25,000 deaths.
- No specific vaccines or antiviral drugs are currently available for DENV treatment.
Purpose of the Study:
- To describe an in vitro assay for the dengue virus serine protease.
- To detail the adaptation of this assay for high-throughput screening (HTS).
- To highlight its utility in identifying potential antiviral compounds.
Main Methods:
- Development of an in vitro assay targeting the DENV serine protease.
- Adaptation of the assay to a high-throughput screening (HTS) format.
- Screening of several thousand chemical compounds using the HTS assay.
Main Results:
- The developed assay was successfully adapted to HTS.
- Thousands of compounds were screened against the viral serine protease.
- The screening identified potential inhibitors of the viral protease.
Conclusions:
- The HTS assay for DENV serine protease is a valuable tool for drug discovery.
- This assay facilitates the identification of novel antiviral agents against dengue.
- Targeting viral protease activity is a promising strategy for DENV therapeutics.
