id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-295075-cqbayzat	Rajnarayanan, Rajendram V.	“Teaching old drugs to kill new bugs”: structure-based discovery of anti-SARS drugs	2004-08-20		.txt	text/plain	3675	208	50	Several old drugs that bind to SARS 3CLpro active site were selected and in silico derivatized to generate covalent irreversible inhibitors with enhanced affinity. Structural conclusions from active site similarity within the coronavirus family and virtual screening on homology models have provided some clues regarding the class of compounds that could interact with SARS protease. The present study employs in silico derivatization as a method to ''teach old drugs to kill new bugs.'' We have designed irreversible covalent inhibitors by selective derivatization of top non-covalent leads, which includes several old drugs especially a class of HIV inhibitors identified from virtual screening. The side chains of His163 and Phe140 and the main-chain atoms of Met165, Glu166, and His172 form the S1 subsite, which confers specificity towards Gln. Thus, specific covalent inhibitors of SARS 3CLpro could be designed by substituting the amino acid at the P1 0 position with a thiol specific reactive organic moiety like chloromethyl ketone.	./cache/cord-295075-cqbayzat.txt	./txt/cord-295075-cqbayzat.txt