id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-336319-8068s9a3	Graci, Jason D.	Mechanisms of action of ribavirin against distinct viruses	2005-11-15		.txt	text/plain	6460	343	36	Indirect mechanisms include reduction in cellular guanosine triphosphate (GTP) pools via inosine monophosphate dehydrogenase (IMPDH) inhibition, and an immunomodulatory effect in which a T-helper type 1 (antiviral) immune response is maintained. Direct mechanisms include inhibition of RNA capping activity, direct inhibition of viral polymerases, and increased mutation frequency via incorporation of ribavirin into newly synthesised genomes leading to error catastrophe. For all three compounds, a linear correlation was noted between GTP pool inhibition and antiviral activity as measured by viral RNA synthesis, as well as antiviral effect measured by reduction in CPE, suggesting that IMPDH inhibition is the primary mechanism of antiviral activity for all three compounds. Although direct biochemical evidence was not obtained, this finding suggested that ribavirin inhibits the capping of RNA genomes, either by interfering with the guanylyltransferase or methyltransferase activities (both of which are thought to be encoded by nsP1) or potentially by being incorporated as a cap analogue, which may impact translation of the RNA.	./cache/cord-336319-8068s9a3.txt	./txt/cord-336319-8068s9a3.txt