N‑[(Thiophen-3-yl)methyl]benzamides as fusion inhibitors of influenza virus targeting H1 and H5 hemagglutinin
Novel antiviral drugs are needed to prepare for infections from influenza A virus (IAV). Here, a series of N-[(thiophen-3-yl)methyl]benzamides, which target the hemagglutinin (HA)-mediated fusion process, is reported. The most active compound, VF-57a, displays a 50% effective concentration (EC50) of...
| Autores: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
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| Tipo de documento: | Artículo |
| Estado: | Published version |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/227287 |
| Acceso en línea: | https://hdl.handle.net/2445/227287 |
| Nivel de acceso: | Acceso abierto |
| Palabra clave: | Inhibidors enzimàtics Influenzavirus Lligands Enzyme inhibitors Influenza viruses Ligands |
| Sumario: | Novel antiviral drugs are needed to prepare for infections from influenza A virus (IAV). Here, a series of N-[(thiophen-3-yl)methyl]benzamides, which target the hemagglutinin (HA)-mediated fusion process, is reported. The most active compound, VF-57a, displays a 50% effective concentration (EC50) of∼0.8 <em>μ</em>M and an antiviral selectivity index >130 in Madin−Darby canine kidney (MDCK) cells infected with A/H1N1 virus. VF-57a proved to be a strong inhibitor of A/H1N1 and A/H5N1 pseudovirus entry (EC50 values of 0.3 and 0.8 <em>μ</em>M, respectively). Cell−cell fusion assays in HA-expressing cells, surface plasmon resonance-based assessment of HA protein refolding, and resistance studies suggested that VF-57a prevents the conformational change of HA at acidic pH. Molecular modeling highlighted the role of the dimethylthiophene moiety and the amide-based tether in anchoring to the binding cavity of HA. Our findings support the further development of this class of IAV fusion inhibitors against A/H1N1 and A/H5N1 viruses. |
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