id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-321131-f8qeytxc	Zhou, Yanchen	Protease inhibitors targeting coronavirus and filovirus entry	2015-04-30		.txt	text/plain	5517	254	45	Abstract In order to gain entry into cells, diverse viruses, including Ebola virus, SARS-coronavirus and the emerging MERS-coronavirus, depend on activation of their envelope glycoproteins by host cell proteases. We report here that the cysteine protease inhibitor K11777, ((2S)-N-[(1E,3S)-1-(benzenesulfonyl)-5-phenylpent-1-en-3-yl]-2-{[(E)-4-methylpiperazine-1-carbonyl] amino}-3-phenylpropanamide) and closely-related vinylsulfones act as broad-spectrum antivirals by targeting cathepsin-mediated cell entry. We report here that the cysteine protease inhibitor K11777, ((2S)-N-[(1E,3S)-1-(benzenesulfonyl)-5-phenylpent-1-en-3-yl]-2-{[(E)-4-methylpiperazine-1-carbonyl] amino}-3-phenylpropanamide) and closely-related vinylsulfones act as broad-spectrum antivirals by targeting cathepsin-mediated cell entry. Cell culture studies demonstrated that endosomal cysteine proteases, in particular cathepsin B (CTSB) and/or L (CTSL), can activate the glycoproteins of filoviruses, SARS-CoV, other coronaviruses, and NiV and Hendra (HeV) viruses to facilitate entry into certain cell lines. The notion that coronaviruses, including SARS-CoV, use both a cathepsin-dependent endosomal pathway and a direct cell-surface serine protease-mediated pathway for entry (Simmons et al., 2013) is supported by our finding that the combination of K11777 and camostat was superior to either compound alone.	./cache/cord-321131-f8qeytxc.txt	./txt/cord-321131-f8qeytxc.txt