Institute of Biochemistry and Molecular Biology I, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany; Leibniz Research Institute for Environmental Medicine, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
Faculty of Biochemistry, Chemistry and Pharmacy, JW Goethe University Frankfurt, Frankfurt am Main, Germany; Pharmacology Consultant, Bad Soden am Taunus, Germany.
Free Radic Biol Med. 2020 Aug 20;156:107-112. doi: 10.1016/j.freeradbiomed.2020.06.032. Epub 2020 Jun 26.
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) 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 (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 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.
依布硒啉是一种有机硒化合物,具有过氧化物和过氧亚硝酸盐还原活性,可作为谷胱甘肽过氧化物酶和过氧化物酶的模拟物。依布硒啉与多种蛋白质巯基反应,形成硒硫键,从而产生抗病毒、抗菌和抗炎等多种作用。冠状病毒 SARS-CoV-2 的主要蛋白酶(M)是一个潜在的药物靶点,对超过 10000 种化合物的筛选发现依布硒啉是 M 的一种特别有前途的抑制剂(Jin, Z. et al. (2020) Nature 582, 289-293)。在这里,我们讨论了依布硒啉与半胱氨酸蛋白酶的反应、依布硒啉在病毒和其他微生物感染中的作用。我们还讨论了依布硒啉在肺炎症中的作用。在对 SARS-CoV-2 中 M 的抑制作用的进一步研究中,如果在体内完整细胞中证实了其抑制作用,依布硒啉可以作为一种很有前途的先导化合物。独立于这种作用,依布硒啉在 COVID-19 中的潜在有益作用归因于对发病机制至关重要的多个靶点,如减轻炎症氧化剂和细胞因子。