id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-255552-k1retwa4	Gassen, Nils C.	Analysis of SARS-CoV-2-controlled autophagy reveals spermidine, MK-2206, and niclosamide as putative antiviral therapeutics	2020-04-15		.txt	text/plain	1208	73	39	Pharmacological modulation of metabolism-dependent cellular pathways such as autophagy reduced propagation of highly pathogenic Middle East respiratory syndrome (MERS)-CoV. In-depth analyses of autophagy signaling and metabolomics indicate that SARS-CoV-2 reduces glycolysis and protein translation by limiting activation of AMP-protein activated kinase (AMPK) and mammalian target of rapamycin complex 1 (mTORC1). Targeting of these pathways by exogenous administration of spermidine, AKT inhibitor MK-2206, and the Beclin-1 stabilizing, antihelminthic drug niclosamide inhibited SARS-CoV-2 propagation by 85, 88, and >99%, respectively. In the case of highly pathogenic Middle East respiratory syndrome 57 (MERS)-CoV, we recently showed that autophagy is limited by a virus-induced AKT1-dependent 58 activation of the E3-ligase S-phase kinase-associated protein 2 (SKP2), which targets the key autophagy 59 initiating protein Beclin-1 (BECN1) for proteasomal degradation (10). Direct blocking of the negative BECN1 regulator SPK2 by previously 175 described inhibitors SMIP004, SMIP004-7, valinomycin, and niclosamide (10) showed SARS-CoV-2 176 growth inhibition from 50 (SMIP004, SMIP004-7) to over 99% in case of valinomycin and niclosamide 177 (Figure 4a, lower panel, Figure S3d,e) .	./cache/cord-255552-k1retwa4.txt	./txt/cord-255552-k1retwa4.txt