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

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.