Potential therapeutic use of ebselen for COVID-19 and other respiratory viral infections

• Published in: Free radical biology & medicine 2020-08, Vol.156, p.107-112
• Main Authors: Sies, Helmut, Parnham, Michael J.
• Format: Article
• Language: English
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Antioxidants - therapeutic use; Antiviral Agents - therapeutic use; Azoles - therapeutic use; Betacoronavirus - drug effects; Betacoronavirus - enzymology; Betacoronavirus - pathogenicity; Binding Sites; Coronavirus 3C Proteases; Coronavirus Infections - drug therapy; Coronavirus Infections - epidemiology; Coronavirus Infections - metabolism; Coronavirus Infections - virology; COVID-19; Cysteine Endopeptidases - chemistry; Cysteine Endopeptidases - metabolism; Cysteine protease; Host-Pathogen Interactions - drug effects; Host-Pathogen Interactions - genetics; Humans; Invited Review; Isoindoles; Lung - drug effects; Lung - metabolism; Lung - pathology; Lung - virology; Lung inflammation; Models, Molecular; Organoselenium compounds; Organoselenium Compounds - therapeutic use; Oxidative Stress - drug effects; Pandemics; Pneumonia, Viral - drug therapy; Pneumonia, Viral - epidemiology; Pneumonia, Viral - metabolism; Pneumonia, Viral - virology; Protease Inhibitors - therapeutic use; Protein Binding; Protein Structure, Secondary; Reactive Oxygen Species - antagonists & inhibitors; Reactive Oxygen Species - metabolism; SARS-CoV-2; Viral Nonstructural Proteins - antagonists & inhibitors; Viral Nonstructural Proteins - chemistry; Viral Nonstructural Proteins - metabolism
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2020.06.032

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. [Display omitted] •Ebselen, an organoselenium compound, exhibits anti-inflammatory and antiviral activity.•Ebselen is a glutathione peroxidase and peroxiredoxin mimetic.•Ebselen reacts with a multitude of protein thiols, resulting in pleiotropic effects.•Ebselen is an effective inhibitor of Mpro, the main protease of SARS-CoV-2.•Ebselen may serve as lead compound for drugs targeting COVID-19.