PT  - JOURNAL ARTICLE
AU  - Zmudzinski, Mikolaj
AU  - Rut, Wioletta
AU  - Olech, Kamila
AU  - Granda, Jarosław
AU  - Giurg, Mirosław
AU  - Burda-Grabowska, Małgorzata
AU  - Zhang, Linlin
AU  - Sun, Xinyuanyuan
AU  - Lv, Zongyang
AU  - Nayak, Digant
AU  - Kesik-Brodacka, Malgorzata
AU  - Olsen, Shaun K.
AU  - Hilgenfeld, Rolf
AU  - Drag, Marcin
TI  - Ebselen derivatives are very potent dual inhibitors of SARS-CoV-2 proteases - PL<sup>pro</sup> and M<sup>pro</sup> in in vitro studies
AID  - 10.1101/2020.08.30.273979
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.08.30.273979
4099  - http://biorxiv.org/content/early/2020/08/31/2020.08.30.273979.short
4100  - http://biorxiv.org/content/early/2020/08/31/2020.08.30.273979.full
AB  - Proteases encoded by SARS-CoV-2 constitute a promising target for new therapies against COVID-19. SARS-CoV-2 main protease (Mpro, 3CLpro) and papain-like protease (PLpro) are responsible for viral polyprotein cleavage - a process crucial for viral survival and replication. Recently it was shown that 2-phenylbenzisoselenazol-3(2H)-one (ebselen), an organoselenium anti-inflammatory small-molecule drug, is a potent, covalent inhibitor of both the proteases and its potency was evaluated in enzymatic and anti-viral assays. In this study, we screened a collection of 23 ebselen derivatives for SARS-CoV-2 PLpro and Mpro inhibitors. Our studies revealed that ebselen derivatives are potent inhibitors of both the proteases. We identified three PLpro and four Mpro inhibitors superior to ebselen. Our work shows that ebselen constitutes a promising platform for development of new antiviral agents targeting both SARS-CoV-2 PLpro and Mpro.Competing Interest StatementThe authors have declared no competing interest.