tetano
Editor, Senior Moderator
Antiviral Res. 2013 Jun 22. pii: S0166-3542(13)00163-0. doi: 10.1016/j.antiviral.2013.06.006. [Epub ahead of print]
Role of the viral hemagglutinin in the anti-influenza virus activity of newly synthesized polycyclic amine compounds.
Torres E, Duque MD, Vanderlinden E, Ma C, Pinto LH, Camps P, Froeyen M, V?zquez S, Naesens L.
Source
Laboratori de Qu?mica Farmac?utica (Unitat Associada al CSIC), Facultat de Farm?cia, and Institute of Biomedicine (IBUB), Universitat de Barcelona, Av. Diagonal 643, Barcelona E-08028, Spain.
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[7.6.0.01,5.05,12.06,10.011,15]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.
Copyright ? 2013. Published by Elsevier B.V.
PMID:
23800838
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23800838
Role of the viral hemagglutinin in the anti-influenza virus activity of newly synthesized polycyclic amine compounds.
Torres E, Duque MD, Vanderlinden E, Ma C, Pinto LH, Camps P, Froeyen M, V?zquez S, Naesens L.
Source
Laboratori de Qu?mica Farmac?utica (Unitat Associada al CSIC), Facultat de Farm?cia, and Institute of Biomedicine (IBUB), Universitat de Barcelona, Av. Diagonal 643, Barcelona E-08028, Spain.
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[7.6.0.01,5.05,12.06,10.011,15]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.
Copyright ? 2013. Published by Elsevier B.V.
PMID:
23800838
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23800838