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Authors: Welker, Armin
Kersten, Christian
Müller, Christin
Madhugiri, Ramakanth
Zimmer, Collin
Müller, Patrick
Zimmermann, Robert
Hammerschmidt, Stefan
Maus, Hannah
Ziebuhr, John
Sotriffer, Christoph
Schirmeister, Tanja
Title: Structure-activity relationships of benzamides and isoindolines designed as SARS-CoV protease inhibitors effective against SARS-CoV-2
Online publication date: 28-Jun-2021
Language: english
Abstract: Inhibition of coronavirus (CoV)-encoded papain-like cysteine proteases (PLpro) represents an attractive strategy to treat infections by these important human pathogens. Herein we report on structure-activity relationships (SAR) of the noncovalent active-site directed inhibitor (R)-5-amino-2-methyl-N-(1-(naphthalen-1-yl)ethyl) benzamide (2 b), which is known to bind into the S3 and S4 pockets of the SARS-CoV PLpro. Moreover, we report the discovery of isoindolines as a new class of potent PLpro inhibitors. The studies also provide a deeper understanding of the binding modes of this inhibitor class. Importantly, the inhibitors were also confirmed to inhibit SARS-CoV-2 replication in cell culture suggesting that, due to the high structural similarities of the target proteases, inhibitors identified against SARS-CoV PLpro are valuable starting points for the development of new pan-coronaviral inhibitors.
DDC: 570 Biowissenschaften
570 Life sciences
610 Medizin
610 Medical sciences
Institution: Johannes Gutenberg-Universität Mainz
Department: FB 09 Chemie, Pharmazie u. Geowissensch.
Place: Mainz
Version: Published version
Publication type: Zeitschriftenaufsatz
License: CC BY
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Journal: ChemMedChem
Pages or article number: 340
Publisher: Wiley-VCH
Publisher place: Weinheim u.a.
Issue date: 2021
ISSN: 1860-7187
Publisher URL:
Publisher DOI: 10.1002/cmdc.202000548
Appears in collections:JGU-Publikationen

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