id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-346658-ij5sr88p	Hilgenfeld, Rolf	Sometimes Intermediates Do the Job!	2006-04-07		.txt	text/plain	1196	73	60	The mode of binding of this inhibitor to the target enzyme was found to be related (although not identical) to what had been seen earlier in a complex between the rhinovirus (HRV-2) 3C proteinase and compound AG7088 (Figure 1A) , a vinylogous ethyl ester developed by Agouron Inc. The structural insight along with information on the flexibility of the enzyme [9] enabled researchers world-wide to use structure-based design [5] and virtual screening methods [10] to prepare new inhibitors of the SARS-CoV M pro . Several lopinavir derivatives showed somewhat improved binding affinities, but it came as a big surprise that some of the intermediate benzotriazole esters resulting from the activation of the acid components by HBTU were nanomolar inhibitors of the M pro ! The discovery of compounds binding noncovalently to the M pro may, in the end, constitute a more important milestone on the way to clinically useful inhibitors of the coronavirus main proteinase than identification of the acylating agents.	./cache/cord-346658-ij5sr88p.txt	./txt/cord-346658-ij5sr88p.txt