Development of iminosugar-based glycosidase inhibitors as drug candidates for SARS-CoV-2 virus via molecular modelling and in vitro studies.

ABSTRACT: 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 = 1.94 µM in A549-ACE2 cells against Omicron BA.1 strain). However, galactosidase inhibitors did not exhibit antiviral activity, whereas mannosidase inhibitors w

SUBMITTER: Ferjancic Z 

PROVIDER: S-EPMC11721942 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature