A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV2 main protease

Effective SARS-CoV-2 antiviral drugs are desperately needed. The SARS-CoV-2 main protease (Mpro) appears as an attractive target for drug development. We show that the existing pharmacopeia contains many drugs with potential for therapeutic repurposing as selective and potent inhibitors of SARS-CoV-2 Mpro. We screened a collection of similar to 6,070 drugs with a previous history of use in humans for compounds that inhibit the activity of Mpro in vitro and found similar to 50 compounds with activity against Mpro. Subsequent dose validation studies demonstrated 8 dose responsive hits with an IC50 <= 50 mu M. Hits from our screen are enriched with hepatitis C NS3/4A protease targeting drugs including boceprevir, ciluprevir. narlaprevir, and telaprevir. This work suggests previous large-scale commercial drug development initiatives targeting hepatitis C NS3/4A viral protease should be revisited because some previous lead compounds may be more potent against SARS-CoV-2 Mpro than boceprevir and suitable for rapid repurposing.

Automated summary

Effective SARS-CoV-2 antiviral drugs are urgently needed, and study identified existing drugs with potential for therapeutic repurposing against SARS-CoV-2. The findings suggest that previous drug development initiatives targeting hepatitis C NS3/4A viral protease should be reconsidered, as some compounds may be more potent against SARS-CoV-2 Mpro than boceprevir.