Vesicular Stomatitis Virus as a Platform for Protease Activity Measurements

Area of Science:

• Virology
• Drug Discovery
• Molecular Biology

Background:

• Protease inhibitors are vital antiviral medications effective against viruses like HIV, HCV, and SARS-CoV-2.
• Identifying new protease inhibitors is crucial for developing next-generation antiviral therapies.
• Robust screening platforms are essential for efficient drug discovery.

Purpose of the Study:

• To develop and present novel cell- and virus replicon-based platforms for screening protease inhibitors.
• To establish efficient methods for identifying potential antiviral drug candidates.

Main Methods:

• Genetically modifying vesicular stomatitis virus (a model Rhabdoviridae virus) to create screening platforms.
• Utilizing Mpro-On and -Off assays, including variations with luciferase reporters and fluorescence-activated cell sorting (FACS) readouts.
• Implementing protocols for virus production and kinetic measurements.

Main Results:

• Successful development of versatile cell- and virus replicon-based screening platforms.
• Demonstration of multiple assay formats (e.g., luciferase, FACS) for inhibitor screening.
• Establishment of methods for virus production and kinetic analysis.

Conclusions:

• The described platforms offer powerful tools for the high-throughput screening of protease inhibitors.
• These methods facilitate the identification of novel antiviral compounds.
• The developed system advances the search for effective treatments against viral infections.