Title: Role of the viral hemagglutinin in the anti-influenza virus activity of newly synthesized polycyclic amine compounds
Authors: Torres, Eva ×
Duque, María D
Vanderlinden, Evelien
Ma, Chunlong
Pinto, Lawrence H
Camps, Pelayo
Froeyen, Mathy
Vázquez, Santiago
Naesens, Lieve #
Issue Date: Sep-2013
Publisher: Elsevier/North-Holland
Series Title: Antiviral Research vol:99 issue:3 pages:281-91
Article number: S0166-3542(13)00163-0
Abstract: We here report on the synthesis of new series of polycyclic amines initially designed as ring-rearranged analogs of amantadine and featuring pentacyclo, hexacyclo, and octacyclo rings. A secondary amine, 3-azahexacyclo[,5).0(5,12).0(6,10).0(11,15)]pentadeca-7,13-diene, 3, effectively inhibited A/M2 proton channel function, and, moreover, possessed dual activity against an A/H3N2 virus carrying a wild-type A/M2 proton channel, as well as an amantadine-resistant A/H1N1 virus. Among the polycyclic amines that did not inhibit influenza A/M2 proton channel function, several showed low-micromolar activity against tested A/H1N1 strains (in particular, the A/PR/8/34 strain), but not A/H3N2 influenza viruses. A/PR/8/34 mutants selected for resistance to these compounds possessed mutations in the viral hemagglutinin that markedly increased the hemolysis pH. Our data suggest that A/H1N1 viruses such as the A/PR/8/34 strain are particularly sensitive to a subtle increase in the endosomal pH, as caused by the polycyclic amine compounds.
ISSN: 0166-3542
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Medicinal Chemistry (Rega Institute)
× corresponding author
# (joint) last author

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