Zorana Ferjancic, Filip Bihelovic, Bojan Vulovic, Radomir Matovic, Milena Trmcic, Aleksandar Jankovic, Milos Pavlovic, Filip Djurkovic, Radivoje Prodanovic, Aleksandra Djurdjevic Djelmas, Nevena Kalicanin, Mario Zlatovic, Dusan Sladic, Thomas Vallet, Marco Vignuzzi, Radomir N Saicic
We developed new iminosugar-based glycosidase inhibitors against SARS-CoV-2. Known drugs (miglustat, migalastat, miglitol, and swainsonine) were chosen as lead compounds to develop three classes of glycosidase inhibitors (α-glucosidase, α-galactosidase, and mannosidase). Molecular modelling of the lead compounds, synthesis of the compounds with the highest docking scores, enzyme inhibition tests, and in vitro antiviral assays afforded rationally designed inhibitors. Two highly active α-glucosidase inhibitors were discovered, where one of them is the most potent iminosugar-based anti-SARS-CoV-2 agent to date (EC90 = 1...
December 2024: Journal of Enzyme Inhibition and Medicinal Chemistry