RT Journal Article
SR Electronic
T1 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
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.08.30.273979
DO 10.1101/2020.08.30.273979
A1 Zmudzinski, Mikolaj
A1 Rut, Wioletta
A1 Olech, Kamila
A1 Granda, Jarosław
A1 Giurg, Mirosław
A1 Burda-Grabowska, Małgorzata
A1 Zhang, Linlin
A1 Sun, Xinyuanyuan
A1 Lv, Zongyang
A1 Nayak, Digant
A1 Kesik-Brodacka, Malgorzata
A1 Olsen, Shaun K.
A1 Hilgenfeld, Rolf
A1 Drag, Marcin
YR 2020
UL http://biorxiv.org/content/early/2020/08/31/2020.08.30.273979.abstract
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.