id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-259374-m7q1roay	Agostini, Maria L.	Small-Molecule Antiviral β-d-N(4)-Hydroxycytidine Inhibits a Proofreading-Intact Coronavirus with a High Genetic Barrier to Resistance	2019-11-26		.txt	text/plain	6093	357	48	Here, we demonstrate that NHC inhibits both murine hepatitis virus (MHV) (50% effective concentration [EC(50)] = 0.17 μM) and Middle East respiratory syndrome CoV (MERS-CoV) (EC(50) = 0.56 μM) with minimal cytotoxicity. Here, we demonstrate the potent antiviral activity of a broad-spectrum ribonucleoside analogue, β-d-N(4)-hydroxycytidine (NHC), against two divergent CoVs. Viral proofreading activity does not markedly impact sensitivity to NHC inhibition, suggesting a novel interaction between a nucleoside analogue inhibitor and the CoV replicase. To directly test the effect of NHC treatment on the mutational burden, we treated WT MHV with increasing concentrations of NHC and performed full-genome next-generation sequencing (NGS) on viral populations released after a single round of infection. Our results indicate that NHC decreases the titers of both WT and ExoN(Ϫ) MHV in a dose-dependent manner but that ExoN(Ϫ) MHV demonstrates a statistically Passage in the presence of NHC yields low-level resistance associated with multiple transition mutations.	./cache/cord-259374-m7q1roay.txt	./txt/cord-259374-m7q1roay.txt