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

Maybe you want to get familiar with ebselen?

Ebselen, an anti-inflammatory antioxidant, was originally developed by Daiichi Sankyo, in Japan, to treat patients who had suffered a stroke. But the compound was never marketed and has since come off patent. It’s also part of the National Institutes of Health Clinical Collection—several hundred small molecules that have, to some extent, gone through the gamut of human clinical trials and have been found to be safe, but never reached final FDA approval.

• ebselen (10 posts to December 2012)

 

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

Author links open overlay panelHelmutSies^ab

Michael J.Parnham^cd

https://doi.org/10.1016/j.freeradbiomed.2020.06.032Get rights and content

Highlights

•

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.

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 (M^pro) 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 M^pro (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 M^pro 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.

Graphical abstract

1. Download : Download high-res image (201KB)
2. Download : Download full-size image