Superior inhibition of influenza virus hemagglutinin-mediated fusion by indole-substituted spirothiazolidinones

Cihan-Ustundag G. , Zopun M., Vanderlinden E., Ozkirimli E., Persoons L., Capan G., ...More

BIOORGANIC & MEDICINAL CHEMISTRY, vol.28, no.1, 2020 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 28 Issue: 1
  • Publication Date: 2020
  • Doi Number: 10.1016/j.bmc.2019.115130


The influenza virus hemagglutinin (HA) mediates membrane fusion after viral entry by endocytosis. The fusion process requires drastic low pH-induced HA refolding and is prevented by arbidol and tert-butylhydroquinone (TBHQ). We here report a class of superior inhibitors with indole-substituted spirothiazolidinone structure. The most active analogue 5f has an EC50 value against influenza A/H3N2 virus of 1 nM and selectivity index of almost 2000. Resistance data and in silico modeling indicate that 5f combines optimized fitting in the TBHQ/arbidol HA binding pocket with a capability for endosomal accumulation. Both criteria appear relevant to achieve superior inhibitors of HA-mediated fusion.