Identification of ebselen and its analogues as potent covalent inhibitors of papain-like protease from SARS-CoV-2

Abstract An efficient treatment against a COVID-19 disease, caused by the novel coronavirus SARS-CoV-2 (CoV2), remains a challenge. The papain-like protease (PLpro) from the human coronavirus is a protease that plays a critical role in virus replication. Moreover, CoV2 uses this enzyme to modulate t...

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Autores principales:	Ewelina Weglarz-Tomczak, Jakub M. Tomczak, Michał Talma, Małgorzata Burda-Grabowska, Mirosław Giurg, Stanley Brul
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d9f5c84dfce444628997569956549aae
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spelling	oai:doaj.org-article:d9f5c84dfce444628997569956549aae2021-12-02T14:26:54ZIdentification of ebselen and its analogues as potent covalent inhibitors of papain-like protease from SARS-CoV-210.1038/s41598-021-83229-62045-2322https://doaj.org/article/d9f5c84dfce444628997569956549aae2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83229-6https://doaj.org/toc/2045-2322Abstract An efficient treatment against a COVID-19 disease, caused by the novel coronavirus SARS-CoV-2 (CoV2), remains a challenge. The papain-like protease (PLpro) from the human coronavirus is a protease that plays a critical role in virus replication. Moreover, CoV2 uses this enzyme to modulate the host’s immune system to its own benefit. Therefore, it represents a highly promising target for the development of antiviral drugs. We used Approximate Bayesian Computation tools, molecular modelling and enzyme activity studies to identify highly active inhibitors of the PLpro. We discovered organoselenium compounds, ebselen and its structural analogues, as a novel approach for inhibiting the activity of PLproCoV2. Furthermore, we identified, for the first time, inhibitors of PLproCoV2 showing potency in the nanomolar range. Moreover, we found a difference between PLpro from SARS and CoV2 that can be correlated with the diverse dynamics of their replication, and, putatively to disease progression.Ewelina Weglarz-TomczakJakub M. TomczakMichał TalmaMałgorzata Burda-GrabowskaMirosław GiurgStanley BrulNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ewelina Weglarz-Tomczak Jakub M. Tomczak Michał Talma Małgorzata Burda-Grabowska Mirosław Giurg Stanley Brul Identification of ebselen and its analogues as potent covalent inhibitors of papain-like protease from SARS-CoV-2
description	Abstract An efficient treatment against a COVID-19 disease, caused by the novel coronavirus SARS-CoV-2 (CoV2), remains a challenge. The papain-like protease (PLpro) from the human coronavirus is a protease that plays a critical role in virus replication. Moreover, CoV2 uses this enzyme to modulate the host’s immune system to its own benefit. Therefore, it represents a highly promising target for the development of antiviral drugs. We used Approximate Bayesian Computation tools, molecular modelling and enzyme activity studies to identify highly active inhibitors of the PLpro. We discovered organoselenium compounds, ebselen and its structural analogues, as a novel approach for inhibiting the activity of PLproCoV2. Furthermore, we identified, for the first time, inhibitors of PLproCoV2 showing potency in the nanomolar range. Moreover, we found a difference between PLpro from SARS and CoV2 that can be correlated with the diverse dynamics of their replication, and, putatively to disease progression.
format	article
author	Ewelina Weglarz-Tomczak Jakub M. Tomczak Michał Talma Małgorzata Burda-Grabowska Mirosław Giurg Stanley Brul
author_facet	Ewelina Weglarz-Tomczak Jakub M. Tomczak Michał Talma Małgorzata Burda-Grabowska Mirosław Giurg Stanley Brul
author_sort	Ewelina Weglarz-Tomczak
title	Identification of ebselen and its analogues as potent covalent inhibitors of papain-like protease from SARS-CoV-2
title_short	Identification of ebselen and its analogues as potent covalent inhibitors of papain-like protease from SARS-CoV-2
title_full	Identification of ebselen and its analogues as potent covalent inhibitors of papain-like protease from SARS-CoV-2
title_fullStr	Identification of ebselen and its analogues as potent covalent inhibitors of papain-like protease from SARS-CoV-2
title_full_unstemmed	Identification of ebselen and its analogues as potent covalent inhibitors of papain-like protease from SARS-CoV-2
title_sort	identification of ebselen and its analogues as potent covalent inhibitors of papain-like protease from sars-cov-2
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d9f5c84dfce444628997569956549aae
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Identification of ebselen and its analogues as potent covalent inhibitors of papain-like protease from SARS-CoV-2

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