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-...

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Autores principales:	Jeremy D Baker, Rikki L Uhrich, Gerald C Kraemer, Jason E Love, Brian C Kraemer
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/895a0ece70cf42ddbee160139b5c757c
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spelling	oai:doaj.org-article:895a0ece70cf42ddbee160139b5c757c2021-12-02T20:15:50ZA drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV2 main protease.1932-620310.1371/journal.pone.0245962https://doaj.org/article/895a0ece70cf42ddbee160139b5c757c2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0245962https://doaj.org/toc/1932-6203Effective 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.Jeremy D BakerRikki L UhrichGerald C KraemerJason E LoveBrian C KraemerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 2, p e0245962 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jeremy D Baker Rikki L Uhrich Gerald C Kraemer Jason E Love Brian C Kraemer A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV2 main protease.
description	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.
format	article
author	Jeremy D Baker Rikki L Uhrich Gerald C Kraemer Jason E Love Brian C Kraemer
author_facet	Jeremy D Baker Rikki L Uhrich Gerald C Kraemer Jason E Love Brian C Kraemer
author_sort	Jeremy D Baker
title	A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV2 main protease.
title_short	A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV2 main protease.
title_full	A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV2 main protease.
title_fullStr	A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV2 main protease.
title_full_unstemmed	A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV2 main protease.
title_sort	drug repurposing screen identifies hepatitis c antivirals as inhibitors of the sars-cov2 main protease.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/895a0ece70cf42ddbee160139b5c757c
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A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV2 main protease.

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