Structure-Activity Studies Reveal Scope for Optimisation of Ebselen-Type Inhibition of SARS-CoV-2 Main Protease

Siegfried T D Thun-Hohenstein; Timothy F Suits; Tika R Malla; Anthony Tumber; Lennart Brewitz; Hani Choudhry; Eidarus Salah; Christopher J Schofield

doi:10.1002/cmdc.202100582

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Structure-Activity Studies Reveal Scope for Optimisation of Ebselen-Type Inhibition of SARS-CoV-2 Main Protease

Journal article

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Structure-Activity Studies Reveal Scope for Optimisation of Ebselen-Type Inhibition of SARS-CoV-2 Main Protease

Siegfried T D Thun-Hohenstein, Timothy F Suits, Tika R Malla, Anthony Tumber, Lennart Brewitz, Hani Choudhry, Eidarus Salah and Christopher J Schofield

ChemMedChem, Vol.17(4), pp.e202100582-n/a

16/02/2022

DOI: https://doi.org/10.1002/cmdc.202100582

PMID: 34850566

Abstract

Coronavirus 3C Proteases - antagonists & inhibitors

COVID-19 - virology

Humans

Isoindoles - chemistry

Isoindoles - pharmacology

Organoselenium Compounds - chemistry

Organoselenium Compounds - pharmacology

Protease Inhibitors - chemistry

Protease Inhibitors - pharmacology

SARS-CoV-2 - enzymology

Structure-Activity Relationship

The reactive organoselenium compound ebselen is being investigated for treatment of coronavirus disease 2019 (COVID-19) and other diseases. We report structure-activity studies on sulfur analogues of ebselen with the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) main protease (M ), employing turnover and protein-observed mass spectrometry-based assays. The results reveal scope for optimisation of ebselen/ebselen derivative- mediated inhibition of M , particularly with respect to improved selectivity.

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Title: Structure-Activity Studies Reveal Scope for Optimisation of Ebselen-Type Inhibition of SARS-CoV-2 Main Protease
Creators - without role: Siegfried T D Thun-Hohenstein - University of Oxford
Timothy F Suits - University of Oxford
Tika R Malla - University of Oxford
Anthony Tumber - University of Oxford
Lennart Brewitz - University of Oxford
Hani Choudhry - University of Oxford
Eidarus Salah - King Abdulaziz University
Christopher J Schofield - University of Oxford
Publication Details: ChemMedChem, Vol.17(4), pp.e202100582-n/a
Grant note: Wellcome Trust 106244/Z/14/Z / Wellcome Trust BB/M011224/1 / Biotechnology and Biological Research Council, Cancer Research UK Oxford Covid Development Fund King Abdulaziz University, Saudi Arabia
Identifiers: 9939833908331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article