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Structure-Activity Studies Reveal Scope for Optimisation of Ebselen-Type Inhibition of SARS-CoV-2 Main Protease |
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| Authors: | Siegfried T D Thun-Hohenstein Timothy F Suits Tika R Malla Dr Anthony Tumber Dr Lennart Brewitz Dr Hani Choudhry Eidarus Salah Prof Christopher J Schofield |
| Affiliation: | 1. Department of Chemistry, University of Oxford, Chemistry Research Laboratory and the Ineos Oxford Institute for Antimicrobial Research, 12 Mansfield Road, Oxford, OX1 3TA UK;2. Department of Biochemistry, Center for Artificial Intelligence in Precision Medicines, King Abdulaziz University, Jeddah, Saudi Arabia |
| Abstract: | 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 (Mpro), employing turnover and protein-observed mass spectrometry-based assays. The results reveal scope for optimisation of ebselen/ebselen derivative- mediated inhibition of Mpro, particularly with respect to improved selectivity. |
| Keywords: | Mpro inhibition SARS-CoV-2 COVID-19 ebselen ebsulfur nucleophilic cysteine protease |