id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-340331-51yq1rdo	Tonelli, Michele	Host dihydrofolate reductase (DHFR)-directed cycloguanil analogues endowed with activity against influenza virus and respiratory syncytial virus	2017-07-28		.txt	text/plain	6160	285	42	We have identified a series of 1-aryl-4,6-diamino-1,2-dihydrotriazines, structurally related to the antimalarial drug cycloguanil, as new inhibitors of influenza A and B virus and respiratory syncytial virus (RSV) via targeting of the host dihydrofolate reductase (DHFR) enzyme. The compounds, object of the present study, are characterized by the 1-aryl-4,6-diamino-1,2-dihydrotriazine scaffold, such as the cited cycloguanil, which was identified by us as prototype (1) of a new class of antiviral agents exploiting a host DHFR inhibition mechanism. Since host cell DHFR inhibition seemed the plausible explanation for the observed antiviral effect, we performed a combination experiment in which RSV-infected HeLa cells were exposed to compound 14 in combination with different concentrations of the natural DHFR substrate dihydrofolic acid ( reaction has a much higher impact on virus replication than on cell growth, which concurs with the promising antiviral selectivity of our host-directed DHFR inhibitors. The interesting dual activity of the 1-aryl-4,6-diamino-1,2dihydrotriazines against influenza and respiratory syncytial viruses, via inhibition of the cellular (human) DHFR enzyme, points to this host factor as a new therapeutic target for these two respiratory viruses.	./cache/cord-340331-51yq1rdo.txt	./txt/cord-340331-51yq1rdo.txt