GRL-0617 is a cell penetrant non-cytotoxic and potent inhibitor of the SARS-CoV -2 papain-like protease (SCoV2-PLpro) and SCoV-PLpro. GRL-0617 reversibly binds to SCoV2-PLpro and disrupts its interaction with Interferon-stimulated gene 15 (ISG15). GRL-0617 poorly affects (> 100 μM) the activities of MERS PLpro, a series of cysteine proteases, including the human deubiquitinating enzymes HAUSP, USP18, UCH-L1, UCH-L3, and a papain-like protease (PLP2) from the human coronavirus NL63. GRL-0617 suppress SARS-CoV-2 infection and promote anti-viral immunity.
cell penetrant non-cytotoxic and potent inhibitor of the SARS-CoV -2 papain-like protease (SCoV2-PLpro) and SCoV-Plpro
Proceedings of the National Academy of Sciences of the United States of America, 105(42), 16119-16124 (2008-10-15)
We report the discovery and optimization of a potent inhibitor against the papain-like protease (PLpro) from the coronavirus that causes severe acute respiratory syndrome (SARS-CoV). This unique protease is not only responsible for processing the viral polyprotein into its functional
The papain-like protease PLpro is an essential coronavirus enzyme that is required for processing viral polyproteins to generate a functional replicase complex and enable viral spread1,2. PLpro is also implicated in cleaving proteinaceous post-translational modifications on host proteins as an
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