posted on 2017-12-08, 00:00authored byRosana Leiva, Marta Barniol-Xicota, Sandra Codony, Tiziana Ginex, Evelien Vanderlinden, Marta Montes, Michael Caffrey, F. Javier Luque, Lieve Naesens, Santiago Vázquez
Two
series of easily accessible anilines were identified as inhibitors
of influenza A virus subtype H1N1, and extensive chemical synthesis
and analysis of the structure–activity relationship were performed.
The compounds were shown to interfere with low pH-induced membrane
fusion mediated by the H1 and H5 (group 1) hemagglutinin (HA) subtypes.
A combination of virus resistance, HA interaction, and molecular dynamics
simulation studies elucidated the binding site of these aniline-based
influenza fusion inhibitors, which significantly overlaps with the
pocket occupied by some H3 HA-specific inhibitors, indicating the
high relevance of this cavity for drug design.