Recent Advances in Virtual Screening for Cholinesterase Inhibitors

Alzheimer's disease (AD) is a significant health crisis, and current treatments provide only limited benefits to cognition at the cost of serious side effects. Recently, virtual screening techniques such as ligand-based virtual screening (LBVS) and structure-based virtual screening (SBVS) have emerged as powerful drug discovery tools for identifying potential ligands of a biological target from a large database of chemical structures. The cholinesterases are an AD target particularly well suited for drug discovery using virtual screening due to their well-characterized active sites and comprehensive understanding of the structure-activity relationships of existing inhibitors. Over the last 5 years (2015-2020), at least 15 studies have used virtual screening techniques to discover potent new cholinesterase inhibitors. Herein we review how LBVS and SBVS have been applied individually or in tandem to discover novel acetylcholinesterase and butyrylcholinesterase inhibitors for AD, and highlight the need to confirm in vitro activity of screening compounds.

Automated summary

Virtual screening techniques, such as LBVS and SBVS, have emerged as powerful tools for drug discovery in Alzheimer’s disease (AD). Cholinesterases, well-suited for virtual screening, have been the target of numerous studies utilizing these techniques to discover novel inhibitors. Confirmation of the in vitro activity of screening compounds is highlighted as a crucial step in the drug discovery process.