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...
| Authors: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
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| Format: | Article |
| Status: | Published version |
| Publication date: | 2025 |
| Country: | España |
| Institution: | Universidad de Barcelona |
| Repository: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/227287 |
| Online Access: | https://hdl.handle.net/2445/227287 |
| Access Level: | Open access |
| Keyword: | Inhibidors enzimàtics Influenzavirus Lligands Enzyme inhibitors Influenza viruses Ligands |
| _version_ | 1878730174722211840 |
|---|---|
| author | Francesconi, Valeria |
| author2 | Rimaux, Silke Valdivia, Aitor Martín López, Juan Escriche Molina, Celia Mestdagh, Cato Van Berwaer, Ria Schurmans, Lieselotte Verleye, Kaat Noppen, Samuel Lozano, Oscar Stevaert, Annelies Luque Garriga, F. Xavier Niesens, Lieve Vázquez Cruz, Santiago |
| author2_role | author author author author author author author author author author author author author author |
| author_browse | Escriche Molina, Celia Francesconi, Valeria Lozano, Oscar Luque Garriga, F. Xavier Martín López, Juan Mestdagh, Cato Niesens, Lieve Noppen, Samuel Rimaux, Silke Schurmans, Lieselotte Stevaert, Annelies Valdivia, Aitor Van Berwaer, Ria Verleye, Kaat Vázquez Cruz, Santiago |
| author_facet | Francesconi, Valeria Rimaux, Silke Valdivia, Aitor Martín López, Juan Escriche Molina, Celia Mestdagh, Cato Van Berwaer, Ria Schurmans, Lieselotte Verleye, Kaat Noppen, Samuel Lozano, Oscar Stevaert, Annelies Luque Garriga, F. Xavier Niesens, Lieve Vázquez Cruz, Santiago |
| author_role | author |
| collection | Dipòsit Digital de la UB |
| description | 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_16ec1ce6591fa5b9f7b88ace5941a034 |
| institution | Universidad de Barcelona |
| instname_str | Universidad de Barcelona |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:diposit.ub.edu:2445/227287 |
| publishDate | 2025 |
| publishDateSort | 2025 |
| publisher | American Chemical Society |
| publisherStr | American Chemical Society |
| reponame_str | Dipòsit Digital de la UB |
| spelling | N‑[(Thiophen-3-yl)methyl]benzamides as fusion inhibitors of influenza virus targeting H1 and H5 hemagglutinin Francesconi, Valeria Rimaux, Silke Valdivia, Aitor Martín López, Juan Escriche Molina, Celia Mestdagh, Cato Van Berwaer, Ria Schurmans, Lieselotte Verleye, Kaat Noppen, Samuel Lozano, Oscar Stevaert, Annelies Luque Garriga, F. Xavier Niesens, Lieve Vázquez Cruz, Santiago Inhibidors enzimàtics Influenzavirus Lligands Enzyme inhibitors Influenza viruses Ligands 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. American Chemical Society https://hdl.handle.net/2445/227287 |
| spellingShingle | N‑[(Thiophen-3-yl)methyl]benzamides as fusion inhibitors of influenza virus targeting H1 and H5 hemagglutinin Francesconi, Valeria Inhibidors enzimàtics Influenzavirus Lligands Enzyme inhibitors Influenza viruses Ligands |
| status_str | publishedVersion |
| title | N‑[(Thiophen-3-yl)methyl]benzamides as fusion inhibitors of influenza virus targeting H1 and H5 hemagglutinin |
| title_full | N‑[(Thiophen-3-yl)methyl]benzamides as fusion inhibitors of influenza virus targeting H1 and H5 hemagglutinin |
| title_fullStr | N‑[(Thiophen-3-yl)methyl]benzamides as fusion inhibitors of influenza virus targeting H1 and H5 hemagglutinin |
| title_full_unstemmed | N‑[(Thiophen-3-yl)methyl]benzamides as fusion inhibitors of influenza virus targeting H1 and H5 hemagglutinin |
| title_short | N‑[(Thiophen-3-yl)methyl]benzamides as fusion inhibitors of influenza virus targeting H1 and H5 hemagglutinin |
| title_sort | N‑[(Thiophen-3-yl)methyl]benzamides as fusion inhibitors of influenza virus targeting H1 and H5 hemagglutinin |
| topic | Inhibidors enzimàtics Influenzavirus Lligands Enzyme inhibitors Influenza viruses Ligands |
| topic_facet | Inhibidors enzimàtics Influenzavirus Lligands Enzyme inhibitors Influenza viruses Ligands |
| url | https://hdl.handle.net/2445/227287 |