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J Med Chem. 2017 Dec 8. doi: 10.1021/acs.jmedchem.7b00908. [Epub ahead of print]
Aniline-based inhibitors of influenza H1N1 virus acting on hemagglutinin-mediated fusion.
Leiva R, Barniol-Xicota M, Codony S, Ginex T, Vanderlinden E, Montes M, Caffrey M, Luque FJ, Naesens L, Vazquez S.
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.
PMID: 29220568 DOI: 10.1021/acs.jmedchem.7b00908
Aniline-based inhibitors of influenza H1N1 virus acting on hemagglutinin-mediated fusion.
Leiva R, Barniol-Xicota M, Codony S, Ginex T, Vanderlinden E, Montes M, Caffrey M, Luque FJ, Naesens L, Vazquez S.
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.
PMID: 29220568 DOI: 10.1021/acs.jmedchem.7b00908