The papain-like protease (PLpro) is a viable target for the development of antivirals against coronavirus-caused severe acute respiratory syndrome (SARS-CoV). GRL0617 is a potent competitive inhibitor of PLpro with a Ki value of 0.49 ± 0.08μM. The IC50 value of GRL0617 for PLpro activity in vitro is 0.6 ± 0.1μM. The antiviral EC50 value of GRL0617 against SARS-CoV is 14.5 ± 0.8μM. GRL0617 is unlikely to inhibit other human ubiquitin-specific proteases, such as HAUSP, USP18, UCH-L1, UCH-L3, and papain-like protease (IC50 > 100μM)[1]. The in vitro IC50 value of GRL0617 against SARS-CoV-2 PLpro is 2.1 ± 0.2μM[2].
作用机制
GRL0617 binds within the S3 and S4 subsites of PLpro. The interaction between them is stabilized through a pair of hydrogen bonds and a series of hydrophobic interactions[1].
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