In silico Prediction of Binding Affinity Between Test Substances and Enzyme beta-secretase for the Treatment of Alzheimer's Disease

Aniket Gandotra, Ashwani Sharma, Jean Bernard Idoipe


Alzheimer’s disease (AD) is the progressive neurodegenerative disease of ageing that causes severe suffering for patients, including progressive memory loss with difficulty in performing daily activities.[1] FDA-approved drugs for the treatment of Alzheimer’s including tacrine (approved in 1993), donepezil (approved in 1996), rivastigmine (1998), and galantamine (approved in 2001) come with inevitable side effects ranging from diarrhea, vomiting, cough, skin reactions, nausea, pruritis (itching) etc.[2] Thus, the development of potential drug alternatives is necessary. Plant compounds offer numerous alternatives to diminish the advanced and side effects of numerous sorts of diseases, counting Alzheimer's. Simultaneously, plant compound structures, including flavonoids, tannins, polyphenols, triterpenes, sterols, and alkaloids, have anti-inflammatory, antioxidant, anti-amyloidogenic, and anticholinesterase activities.[3] In this study, we selected ß-secretase, 20 FDA-approved drugs and 22 plant compounds and performed docking with the help of Auto Dock VINA to predict their binding affinities to the proteins. The top-ranked compounds were then subject to toxicity analysis using VEGA QSAR. After analyzing the results, it was found that plant compounds have stronger affinity towards the protein in comparison to the FDA-approved drugs. Hesperidin was the plant compoundhaving a stronger affinity to ß-secretase. Also, it was found that Hesperidin, was the only plant compound having a good affinity for the protein. Moreover, after the toxicity prediction, it was found that the top-ranking plant compound was mostly non-mutagenic and non-carcinogenic and active in in-vitro micronucleus activity whereas the results varied for each of the FDA-approved drugs. The purpose of performing molecular docking and toxicity analysis was to understand the affinity of plant compounds and FDA drugs to the potential protein and analyze their toxicity to find a potential candidate targeting Alzheimer’s disease.

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