GRL-0617 is a potent (IC50 = 600 nM) noncovalent inhibitor of severe acute respiratory syndrome-coronavirus papain-like protease (SARS-CoV PLpro). GRL-0617 inhibited SARS-CoV viral replication in Vero E6 cells with no cytotoxicity (EC50 = 15 µM). Inactive against human DUB-like proteases HAUSP, USP18, UCH-L1, UCH-L3, and PLP2. GRL-0617 was recently shown to block SARS-CoV2 replication in CaCo-2 cells (IC50 = 1.50 µM for SCoV2-PLpro), impair the virus-induced cytopathogenic effect, and maintain the antiviral interferon pathway.3
References/Citations
1) Ratia et al. (2008), A noncovalent class of papain-like protease/deubiquitinase inhibitors blocks SARS virus replication; Proc. Natl. Acad. Sci. USA, 105 16119
2) Ghosh et al. (2009), Structure-Based Design, Synthesis, and Biological Evaluation of a Series of Novel and Reversible Inhibitors for the Severe Acute Respiratory Syndrome-Coronavirus Papain-Like Protease; J. Med. Chem. 52 5228
3) Shin et al. (2020),Papain-like protease regulates SARS-CoV2 viral spread and innate immunity; Nature 587 657