Identification of FDA-Approved Drugs That Inhibit SARS-CoV-2 and Human Norovirus Replication

Area of Science:

• Virology
• Drug Discovery
• Molecular Biology

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant global health threat.
• Targeting viral proteases is a key strategy for developing antiviral therapies.
• Identifying existing drugs for repurposing can accelerate treatment development.

Purpose of the Study:

• To identify U.S. Food and Drug Administration (FDA)-approved drugs that inhibit SARS-CoV-2 replication by targeting its 3CL protease (3CLpro).
• To evaluate the antiviral activity of identified compounds against SARS-CoV-2 and human norovirus (HuNoV).

Main Methods:

• Screening of an FDA-approved drug library using a cellular and green fluorescent protein (GFP) reporter-based assay (FlipGFP-3CLpro assay) to assess 3CLpro activity.
• In vitro enzymatic assays and cell-based assays were used to validate compound efficacy against SARS-CoV-2.
• Human intestinal organoids were utilized to test antiviral effects against HuNoV.

Main Results:

• Five FDA-approved drugs (auranofin, endoxifen, netupitant, pimozide, and regorafenib) were identified as hits.
• Three compounds (auranofin, endoxifen, and pimozide) demonstrated dose-dependent inhibition of 3CLpro activity in vitro.
• All five compounds inhibited SARS-CoV-2 replication in cultured cells.
• Four of the five compounds significantly suppressed HuNoV replication in human intestinal organoids.

Conclusions:

• Several FDA-approved drugs show potential as inhibitors of SARS-CoV-2 replication.
• Some identified compounds also exhibit activity against human norovirus, suggesting broad-spectrum antiviral potential.
• These findings warrant further investigation for the development of novel antiviral therapeutics.