Targeting Host Cell Proteases to Prevent SARS-CoV-2 Invasion

Area of Science:

• Virology
• Drug Discovery
• Biochemistry

Background:

• Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes global devastation, with limited definitive treatments.
• Symptomatic management is standard care, while repurposed antivirals have shown limited success.
• Targeting host proteases involved in viral entry presents an attractive therapeutic strategy.

Purpose of the Study:

• To explore the therapeutic potential of inhibiting host proteases crucial for SARS-CoV-2 entry and replication.
• To review existing evidence and hypotheses for using protease inhibitors in COVID-19 treatment.
• To discuss approved drugs and novel compounds targeting proteases like TMPRSS2, cathepsin, and furin.

Main Methods:

• Literature review of studies on host proteases and SARS-CoV-2 pathogenesis.
• Analysis of existing evidence and hypotheses regarding protease inhibitor efficacy.
• Identification of approved drugs and novel compounds investigated for targeting viral entry proteases.

Main Results:

• Proteolytic cleavage of the SARS-CoV-2 spike protein by TMPRSS2 is essential for host cell fusion.
• Other proteases (furin, cathepsins, trypsin) may also play roles in viral entry and replication.
• Several approved drugs (e.g., nafamostat, camostat, bromhexine) and anticoagulants are being investigated as potential protease inhibitors.

Conclusions:

• Inhibitors of host proteases represent a potential therapeutic avenue for managing SARS-CoV-2 infections.
• Repurposing existing drugs offers a faster route to clinical application.
• Further research is needed to validate the efficacy and safety of these agents against COVID-19.