2. Academic Validation
  3. Aniline-Based Inhibitors of Influenza H1N1 Virus Acting on Hemagglutinin-Mediated Fusion

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

  • J Med Chem. 2018 Jan 11;61(1):98-118. doi: 10.1021/acs.jmedchem.7b00908.
Rosana Leiva 1,  Marta Barniol-Xicota 1,  Sandra Codony 1,  Tiziana Ginex 2,  Evelien Vanderlinden 3,  Marta Montes 1,  Michael Caffrey 4,  F Javier Luque 2,  Lieve Naesens 3,  Santiago Vázquez 1
Affiliations

Affiliations

  • 1 Laboratori de Química Farmacèutica (Unitat Associada al CSIC), Facultat de Farmàcia i Ciències de l'Alimentació, and Institute of Biomedicine (IBUB), Universitat de Barcelona , Av. Joan XXIII, 27-31, Barcelona E-08028, Spain.
  • 2 Department of Nutrition, Food Science and Gastronomy, Faculty of Pharmacy and Food Sciences, and Institute of Biomedicine (IBUB), Universitat de Barcelona , Av. Prat de la Riba 171, Santa Coloma de Gramanet E-08921, Spain.
  • 3 Rega Institute for Medical Research, KU Leuven , B-3000 Leuven, Belgium.
  • 4 Department of Biochemistry & Molecular Genetics, University of Illinois at Chicago , 900 South Ashland Avenue, Chicago, Illinois 60607, United States.
PMID: 29220568 DOI: 10.1021/acs.jmedchem.7b00908
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.

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