Year: 2025
Type: article
Abstract: There are concerns on use of Botulinum neurotoxin type A (BoNT/A) as a bioweapon and effective small molecule antidotes to treat toxin poisoning are required. Five phytochemicals with known medicinal properties were evaluated for their ability to bind at the active site of Botulinum neurotoxin A light chain (LC/A). In silico docking studies showed that natural flavonoid Quercetagetin interacts with critical amino acid residues in the catalytic pocket and substrate discriminating sub-site regions of the light chain. Using an in vitro protease assay with a radiolabeled derivative of the native SNAP-25 substrate and recombinant LC/A, we tested the inhibitory potency of the phytochemicals. Quercetagetin was found to inhibit toxin’s protease activity with an IC50 of ~ 26 µM. Our study shows that Quercetagetin displays potential to block BoNT/A, and its core benzopyranone scaffold holds promise for developing useful inhibitors to treat botulism.
Authors: Vaidyanathan VV, Saravanan K, Sistla R, Binz T
Institution: Medizinische Hochschule Hannover
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
Funder: Alexander von Humboldt-Stiftung
OpenAlex ID: W4406273909