Fitxers
Tipus de document
ArticleVersió
Versió publicadaData de publicació
Llicència de publicació
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/227287
N‑[(Thiophen-3-yl)methyl]benzamides as fusion inhibitors of influenza virus targeting H1 and H5 hemagglutinin
Títol de la revista
Director/Tutor
ISSN de la revista
Títol del volum
Recurs relacionat
Resum
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 μM 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 μM, 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.
Matèries
Matèries (anglès)
Citació
Citació
FRANCESCONI, Valeria, et al. N‑[(Thiophen-3-yl)methyl]benzamides as fusion inhibitors of influenza virus targeting H1 and H5 hemagglutinin . Journal of Medicinal Chemistry. 2025. Vol. 68, num. 18491-18518. ISSN 0022-2623. [consulted: 23 of May of 2026]. Available at: https://hdl.handle.net/2445/227287