A high-throughput cell-based screening method for Zika virus protease inhibitor discovery

Area of Science:

• Virology
• Drug Discovery
• Biochemistry

Background:

• Zika virus (ZIKV) presents a persistent global health challenge with potential for widespread outbreaks.
• ZIKV infections can lead to severe neurological issues and congenital abnormalities.
• No vaccines or antiviral treatments are currently approved for ZIKV.

Purpose of the Study:

• To establish a cell-based assay for high-throughput screening (HTS) of potential Zika virus protease inhibitors.
• To identify novel drug candidates targeting the essential ZIKV NS2B-NS3 protease.

Main Methods:

• Developed a novel cell-based assay utilizing a cyclized firefly luciferase reporter system.
• The assay measures the cleavage activity of the ZIKV NS2B-NS3 protease in living cells.
• Validated the assay's performance using known pharmacologic controls and screened a compound library (LOPAC).

Main Results:

• Successfully established and validated a robust cell-based ZIKV protease inhibition assay suitable for HTS.
• Demonstrated the assay's effectiveness in identifying potential inhibitors from a diverse compound library.
• Confirmed the feasibility of using this assay for large-scale screening efforts.

Conclusions:

• The developed assay is a valuable tool for identifying novel Zika virus protease inhibitors.
• This platform facilitates the discovery of much-needed therapeutics for ZIKV infection.
• The study provides a foundation for advancing ZIKV drug development pipelines.