RNA-Dependent RNA Polymerase as a Target for COVID-19 Drug Discovery

Area of Science:

• Virology
• Drug Discovery
• Biochemistry

Background:

• Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes COVID-19, a global health crisis.
• Current therapeutic options are limited, with remdesivir being the only approved treatment under Emergency Use Authorization.
• The viral RNA-dependent RNA polymerase (RdRP) is a key enzyme for SARS-CoV-2 replication and a promising drug target.

Purpose of the Study:

• To review biochemical and cell-based assays for SARS-CoV-2 RNA-dependent RNA polymerase (RdRP).
• To identify methods suitable for high-throughput screening (HTS) to discover novel antiviral therapeutics.
• To explore the potential for repurposing existing drugs against SARS-CoV-2 through RdRP inhibition.

Main Methods:

• Focus on biochemical enzyme assays to measure RdRP activity.
• Discussion of cell-based assays to evaluate RdRP inhibition in a cellular context.
• Emphasis on assays amenable to high-throughput screening for drug discovery.

Main Results:

• Identification of various assay formats for SARS-CoV-2 RdRP.
• Evaluation of assay suitability for screening diverse compound libraries.
• Highlighting the importance of RdRP as a target for selective inhibitor development.

Conclusions:

• Biochemical and cell-based assays are essential tools for discovering SARS-CoV-2 RdRP inhibitors.
• High-throughput screening using these assays can accelerate the development of effective COVID-19 therapeutics.
• Targeting the viral RdRP offers a strategy for developing potent and safe antiviral drugs with minimal host toxicity.