Abstract
In silico analysis and characterization has revolutionized target and drug discovery significantly. Alcohol abuse is a big threat to society, economy and wellbeing of people. It has increased the overall disease and injury burden, globally. Recently, a study revealed a brain protein, Munc13-1 C1 domain to play a significant role in development of alcohol tolerance, by binding to alcohol molecules, eventually leading to Alcohol Use Disorder. The aim of this study was to discover a phytochemical that would attach to our target protein, Munc13-1 C1 domain so that it cannot bind with the alcohol molecules. Munc13-1 3D structure obtained from PDB was docked against a library of compounds by MOE software. Ten phytochemicals based on their binding affinity with the target protein were shortlisted i.e. Tannic Acid, Anemone blue anthocyanin 1, Oolonghomobisflavan B, Diosmin, Oolonghomobisflavan A, Neodiosmin, Blepharocalyxin B, 8-Hydroxyhesperetin, Eupatorin and Monotesone A. However, only 8-Hydroxyhesperetin, Eupatorin and Monotesone A followed Lipinski rules. They were non-toxic and non-carcinogenic according to SwissADME. Moreover, have a good drug-like model score as analysed by Molsoft. Further, in-vivo and invitro examinations are required to inspect their role in reducing alcohol tolerance.
Highlights
Alcohol is an organic substance formed when a hydrogen atom is substituted by a hydroxyl group in a hydrocarbon
Selection of target Protein: After scrutinizing literature review, Munc13-1 C1 domain was selected as the target protein for development of a drug that reduces alcohol tolerance
Once the docking was completed, phytochemicals with best conformations were identified on the basis of Root Mean Square Deviation (RMSD) value and Sscore
Summary
Alcohol is an organic substance formed when a hydrogen atom is substituted by a hydroxyl group in a hydrocarbon. Ethanol is the type of alcohol used in alcoholic beverages. It is a product of fermentation of different sugars by yeast. Drinking problem that becomes severe as defined by The National Institute on Alcohol Abuse and Alcoholism (NIAAA). Alcoholism is a complex problem to treat as it effects a lot of body parts on so many levels. Munc is a phorbol ester-dependent enhancer of spontaneous and evoked neurotransmitters. It is a significant target of presynaptic phorbol ester and diacylglycerol (Betz et al, 1998). According to a new research, Munc that binds to alcohol molecules inside the brain, can be targeted to cure alcoholism. The protein plays a crucial role in the development of tolerance against alcohol
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