Topic: virtual screening

GABA type A receptors (GABAARs) are ligand-gated pentameric ion channels found throughout vertebrate and invertebrate nervous systems. Although their structure and function are highly conserved, they can be selectively modulated. Among insect GABA receptors, the Rdl variant has received significant attention, and recent studies have shown its ability to form functional channels with LCCH3 subunits. Mutations like A302S on GABA Rdl of Drosophila confer resistance to various insecticides. Thus, the search for novel compounds able to avoid this resistance mechanism becomes urgent. Due to a lack o

Gain-of-function variants in the Na+-regulated K+ channel KCNT1 are associated to severe, drug-resistant forms of epilepsy. Quinidine has been used as a KCNT1 blocker, both in vitro and in vivo, though with conflicting clinical outcomes.To identify novel KCNT1 blockers, in the present work an in-house library of >800 compounds underwent a virtual screening based on docking energy scores and similarity to the quinidine bound conformation in a homology model of hKCNT1. Twenty molecules were selected and further screened in vitro using a Tl+-based fluorescent assay in KCNT1-expressing CHO cell