SARS-CoV-2 RNA-dependent RNA polymerase as a therapeutic target for COVID-19

Area of Science:

• Virology
• Drug Discovery
• Medicinal Chemistry

Background:

• The COVID-19 pandemic necessitates rapid development of prevention and treatment strategies.
• RNA-dependent RNA-polymerase (RdRp) is a validated target for antiviral drug development due to its essential role in viral replication and lack of human homologues.
• Drug repurposing offers a faster route to identify safe and effective treatments for severe COVID-19 cases.

Purpose of the Study:

• To review current data and ongoing studies on repurposing drugs targeting SARS-CoV-2 RdRp.
• To assess the potential of existing drugs to inhibit viral replication.
• To inform future drug development strategies for coronaviruses.

Main Methods:

• Literature review of published and ongoing research on SARS-CoV-2 RdRp inhibitors.
• Analysis of drug repurposing candidates with known safety and tolerability profiles.
• Consideration of SARS-CoV-2 exonuclease activity in drug design.

Main Results:

• Several drug repurposing candidates targeting RdRp are under investigation.
• The proofreading exonuclease activity of SARS-CoV-2 may influence the efficacy of chain-terminating inhibitors.
• Delayed termination strategies may be more effective against SARS-CoV-2.

Conclusions:

• Drug repurposing and novel compound design are progressing in parallel to address COVID-19.
• Understanding RdRp activity, including its proofreading function, is crucial for developing effective antivirals.
• Partially effective repurposed drugs could aid in managing severe COVID-19 while awaiting vaccination.
• Knowledge gained from SARS-CoV-2 RdRp can benefit future coronavirus pandemic preparedness.