Aniline-based inhibitors of influenza H1N1 virus acting on hemagglutinin-mediated fusion

J. Med. Chem. 61:98-118, 2018.

Abstract.

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.

A Study of the Activity of Adamantyl Amines against Mutant Influenza A M2 Channels Identified a Polycyclic Cage Amine Triple Blocker, Explored by Molecular Dynamics Simulations and Solid-State NMR

Μarianna Stampolaki, Anja Hoffmann, Kumar Tekwani, Kyriakos Georgiou, Christina Tzitzoglaki, Chunlong Ma, Stefan Becker, Patrick Schmerer, Kristin Döring, Ioannis Stylianakis, Andreea L. Turcu, Jun Wang, Santiago Vázquez, Loren B. Andreas, Michaela Schmidtke, Antonios Kolocouris DOI:…

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