Computational Screening of Phytochemicals against Munc13-1, a Promising target to treat Alcoholism

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.