id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-297787-t9neub6d	Fu, Ziyang	Structural basis for the inhibition of the papain-like protease of SARS-CoV-2 by small molecules	2020-07-18		.txt	text/plain	2152	149	64	The co-crystal structure of SARS-CoV-2 PLpro-C111S in complex with GRL0617 suggests that GRL0617 is a non-covalent inhibitor. The antiviral activity of GRL0617 reveal that PLpro is a promising drug target for therapeutically treating COVID-19. The in-vitro 85 IC50 of GRL0617 against SARS-COV-2 PLpro was 2.1 ± 0.2 μM, suggesting a promising lead 86 compound and therefore it was subjected to further structural and mechanistic studies ( Fig. 2A) . Taken together, our NMR and X-ray analysis indicates that GRL0617 162 is a potent PPI (protein-protein interaction) inhibitor for PLpro blocking the binding of ISG15. Our co-crystal structure of PLpro C111S in complex with the potent 175 inhibitor GRL0617 validated that SARS-COV-2 PLpro is a druggable target. Based on the structure, GRL0617 resides in the S3/S4 site of PLpro, naturally it will also 179 inhibit the processing of viral polyproteins of SARS-CoV-2 since these viral polyproteins share the 180 same substrate cleavage sequence with Ub and ISG15. The SARS-coronavirus papain-like 257 protease: structure, function and inhibition by designed antiviral compounds	./cache/cord-297787-t9neub6d.txt	./txt/cord-297787-t9neub6d.txt