Quercetin inhibits acid-sensing ion channels through a putative binding site in the central vestibular region

Highlights • Quercetin inhibits three subtypes of ASICs in a dose-dependent manner with an IC50 of about 2µM. • In HEK- 293 cells quercetin inhibits low pH- induced calcium entry and cell death. • Effect of quercetin is not membrane mediated as it doesn’t inhibit other channels like NMDA receptor, GABAA receptor, and P2X4 receptor. • In silico and mutation studies identified four residues in the central vestibular region of the channel which seem to interact with Quercetin. • Its specificity and efficacy make it a potential therapeutic candidate for targeting ASICs.