In silico Drug Design of Natural Apolipoprotein E4 Inhibitors for Alzheimer's Disease Management

Background: Alzheimer's disease (AD) is the most common form of dementia among the elderly and one of the most difficult public health issues. The APoE4 allele is the main risk factor for late-onset sporadic AD.Methods: This study chose phytochemicals from Ginkgo biloba because of their well-documented neuroprotective properties. A total of 258 G. biloba compounds were obtained from the LOTUS database and screened against the Apolipoprotein E4 (ApoE4) protein using the in silico method. Physicochemical and ADMET properties prediction assessment was conducted using the ADMETLab 3.0 web tool. Result: The hit compounds quercetin, saccharic acid, acacetin, and L-tyrosine were discovered to strongly bind to ApoE4 protein and interact with key ApoE4 protein residues. In addition, these compounds had several amino acid interactions in common with the control compounds. Furthermore, these four compounds have distinct ADMET profiles, and the expected properties, such as solubility, permeability, and toxicity, fall within acceptable limits, making them potential drug candidates.Conclusion: The compounds (quercetin, saccharic acid, acacetin, and L-tyrosine) can be used as ApoE4 inhibitors to manage AD.Keywords: Alzheimer's disease; dementia; apolipoprotein E4; Ginkgo biloba; drug-likeness