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Abstract Details
A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV2 main protease
PLoS One. 2021 Feb 1;16(2):e0245962. doi: 10.1371/journal.pone.0245962. eCollection 2021.
Jeremy D Baker12, Rikki L Uhrich2, Gerald C Kraemer3, Jason E Love4, Brian C Kraemer1256
Author information
1Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, WA, United States of America.
2Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, United States of America.
3Thomas Jefferson High School, Auburn, WA, United States of America.
4Western Washington Pathology, Tacoma, WA, United States of America.
5Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, United States of America.
6Department of Pathology, University of Washington, Seattle, WA, United States of America.
Abstract
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 ~6,070 drugs with a previous history of use in humans for compounds that inhibit the activity of Mpro in vitro and found ~50 compounds with activity against Mpro. Subsequent dose validation studies demonstrated 8 dose responsive hits with an IC50 ≤ 50 μM. 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.