Identification of Novel Natural BACE1 Inhibitors for Alzheimer's Disease via In Silico Approach

Abstract

Background: Alzheimer's disease (AD) is a neurological ailment that causes progressive memory loss as neurons die. Beta-secretase 1 (BACE1) is a key enzyme in the production of amyloid beta, which is a characteristic of Alzheimer's disease. Developing new BACE1 inhibitors with no cytotoxicity is a promising method to treat AD.Methods: The goal of this study was to find new BACE1 inhibitors by screening natural compounds in the ZINC database against the BACE1 active site. The compounds were screened against BACE1 using the PyRx 0.8 program. The SwissADME web server was used to determine the ADMET properties of hit compounds.Results: The hit compounds ZINC3875408, ZINC4098603, ZINC95561079, ZINC299817515, and ZINC67903362 exhibited higher binding affinities to BACE1 than the control compound AZD3293. The Asp32, Lys224, Tyr198, Thr329, Ile226, Val332, Arg128, Tyr71, Phe108, Lys107, Gly74, Gly13, Gly11, Gln12, Ile110, Trp115, Leu30, and Gly230 were the important binding residues of BACE1 protein with these compounds as well as the control compound. These compounds also have good drug-like qualities.Conclusion: The compounds ZINC3875408, ZINC4098603, ZINC95561079, ZINC299817515, and ZINC67903362 can be used as BACE1 inhibitors to manage AD. However, experimental validation is needed to optimize these compounds as BACE1 inhibitors.Keywords: Alzheimer's Disease; Amyloid Beta; Beta-Secretase 1; Natural Compound