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, E. Salah, Christopher J. Schofield
Abstract
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 (M pro ), employing turnover and protein‐observed mass spectrometry‐based assays. The results reveal scope for optimisation of ebselen/ebselen derivative‐ mediated inhibition of M pro , particularly with respect to improved selectivity.
Topics & Concepts
EbselenProteaseSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)VirologyScope (computer science)Coronavirus disease 2019 (COVID-19)2019-20 coronavirus outbreakCoronavirusChemistryComputational biologyBiologyMedicineComputer scienceEnzymeBiochemistryOutbreakProgramming languagePathologyGlutathioneGlutathione peroxidaseInfectious disease (medical specialty)DiseaseComputational Drug Discovery MethodsSynthesis and biological activityCholinesterase and Neurodegenerative Diseases