id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-329959-4yecwdlo	Lin, Min-Han	Disulfiram can inhibit MERS and SARS coronavirus papain-like proteases via different modes	2017-12-28		.txt	text/plain	5576	319	58	Here we show that a clinically available alcohol-aversive drug, disulfiram, can inhibit the papain-like proteases (PL(pro)s) of MERS-CoV and SARS-CoV. The phenomenon of slow-binding inhibition and the irrecoverability of enzyme activity after removing unbound disulfiram indicate covalent inactivation of SARS-CoV PL(pro) by disulfiram, while synergistic inhibition of MERS-CoV PL(pro) by disulfiram and 6-thioguanine or mycophenolic acid implies the potential for combination treatments using these three clinically available drugs. For the inactivation studies, SARS-CoV PL pro (0.05 μM in 20 mM phosphate buffer, pH 6.5) was incubated with different concentrations of disulfiram and peptide substrate, and enzymatic activity was traced for 5 min. On the other hand, the results of kinetic assays, continued inactivation after the removal of disulfiram, reactivation by reductant, and the phenomenon of slow-binding inhibition suggest that disulfiram may act at the active site of SARS-CoV PL pro , forming a covalent adduct with residue Cys112.	./cache/cord-329959-4yecwdlo.txt	./txt/cord-329959-4yecwdlo.txt