Abstract
Ebselen is an organoselenium compound exhibiting hydroperoxide- and peroxynitrite-reducing activity, acting as a glutathione peroxidase and peroxiredoxin enzyme mimetic. Ebselen reacts with a multitude of protein thiols, forming a selenosulfide bond, which results in pleiotropic effects of antiviral, antibacterial and anti-inflammatory nature. The main protease (Mpro) of the corona virus SARS-CoV-2 is a potential drug target, and a screen with over 10,000 compounds identified ebselen as a particularly promising inhibitor of Mpro (Jin, Z. et al. (2020) Nature 582, 289-293). We discuss here the reaction of ebselen with cysteine proteases, the role of ebselen in infections with viruses and with other microorganisms. We also discuss effects of ebselen in lung inflammation. In further research on the inhibition of Mpro in SARS-CoV-2, ebselen can serve as a promising lead compound, if the inhibitory effect is confirmed in intact cells in vivo. Independently of this action, potential beneficial effects of ebselen in COVID-19 are ascribed to a number of targets critical to pathogenesis, such as attenuation of inflammatory oxidants and cytokines.
Keywords:
Cysteine protease; Lung inflammation; Organoselenium compounds; SARS-CoV-2.
Copyright © 2020 Elsevier Inc. All rights reserved.
MeSH terms
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Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
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Antioxidants / therapeutic use*
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Antiviral Agents / therapeutic use*
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Azoles / therapeutic use*
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Betacoronavirus / drug effects*
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Betacoronavirus / enzymology
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Betacoronavirus / pathogenicity
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Binding Sites
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COVID-19
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Coronavirus 3C Proteases
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Coronavirus Infections / drug therapy*
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Coronavirus Infections / epidemiology
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Coronavirus Infections / metabolism
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Coronavirus Infections / virology
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Cysteine Endopeptidases / chemistry
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Cysteine Endopeptidases / metabolism
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Host-Pathogen Interactions / drug effects
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Host-Pathogen Interactions / genetics
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Humans
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Isoindoles
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Lung / drug effects
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Lung / metabolism
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Lung / pathology
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Lung / virology
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Models, Molecular
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Organoselenium Compounds / therapeutic use*
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Oxidative Stress / drug effects
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Pandemics*
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Pneumonia, Viral / drug therapy*
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Pneumonia, Viral / epidemiology
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Pneumonia, Viral / metabolism
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Pneumonia, Viral / virology
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Protease Inhibitors / therapeutic use
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Protein Binding
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Protein Structure, Secondary
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Reactive Oxygen Species / antagonists & inhibitors
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Reactive Oxygen Species / metabolism
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SARS-CoV-2
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Viral Nonstructural Proteins / antagonists & inhibitors*
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Viral Nonstructural Proteins / chemistry
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Viral Nonstructural Proteins / metabolism
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Antioxidants
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Antiviral Agents
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Azoles
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Isoindoles
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Organoselenium Compounds
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Protease Inhibitors
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Reactive Oxygen Species
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Viral Nonstructural Proteins
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ebselen
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Cysteine Endopeptidases
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Coronavirus 3C Proteases