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Discovery of potent inhibitors of PLproCoV2 by screening a library of selenium-containing compounds

Ewelina Węglarz-Tomczak, Jakub M. Tomczak, Mirosław Giurg, Małgorzata Burda-Grabowska, Stanley Brul
doi: https://doi.org/10.1101/2020.05.20.107052
Ewelina Węglarz-Tomczak
1Swammerdam Institute for Life Sciences, Faculty of Science, University of Amsterdam, the Netherlands
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  • For correspondence: ewelina.weglarz.tomczak@gmail.com
Jakub M. Tomczak
2Department of Computer Science, Faculty of Science, Vrije Universiteit Amsterdam, the Netherlands
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Mirosław Giurg
3Department of Organic and Medicinal Chemistry, Faculty of Chemistry, Wroclaw University of Science and Technology, Wrocław, Poland
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Małgorzata Burda-Grabowska
3Department of Organic and Medicinal Chemistry, Faculty of Chemistry, Wroclaw University of Science and Technology, Wrocław, Poland
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Stanley Brul
1Swammerdam Institute for Life Sciences, Faculty of Science, University of Amsterdam, the Netherlands
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Abstract

A collection of twelve organoselenium compounds, structural analogues of antioxidant drug ebselen were screened for inhibition of the papain-like protease (PLpro) from the acute respiratory syndrome coronavirus 2 (SARS-CoV-2, CoV2). This cysteine protease, being responsible for the hydrolysis of peptide bonds between specific amino acids, plays a critical role in CoV2 replication and in assembly of new viral particles within human cells. The activity of the PLpro CoV2 is essential for the progression of coronavirus disease 2019 (COVID-19) and it constitutes a key target for the development of anti-COVID-19 drugs. Here, we identified four strong inhibitors that bind favorably to the PLpro CoV2 with the IC50 in the nanomolar range.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • A typo in title fixed. A list of authors updated.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted May 21, 2020.
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Discovery of potent inhibitors of PLproCoV2 by screening a library of selenium-containing compounds
Ewelina Węglarz-Tomczak, Jakub M. Tomczak, Mirosław Giurg, Małgorzata Burda-Grabowska, Stanley Brul
bioRxiv 2020.05.20.107052; doi: https://doi.org/10.1101/2020.05.20.107052
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Discovery of potent inhibitors of PLproCoV2 by screening a library of selenium-containing compounds
Ewelina Węglarz-Tomczak, Jakub M. Tomczak, Mirosław Giurg, Małgorzata Burda-Grabowska, Stanley Brul
bioRxiv 2020.05.20.107052; doi: https://doi.org/10.1101/2020.05.20.107052

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