American Chemical Society
Browse
jm7b00908_si_003.pdb (1.82 MB)

Aniline-Based Inhibitors of Influenza H1N1 Virus Acting on Hemagglutinin-Mediated Fusion

Download (1.82 MB)
dataset
posted on 2017-12-08, 00:00 authored by Rosana 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.

History