Targeting key players in Alzheimer’s disease: bioactive compounds from Moringa oleifera , Desmodium gangeticum , and Centella asiatica as potential therapeutics

to inhibit the activity of BACE1. We have identified nine compounds out of 73 compounds filtered out from the three plants showing high affinity with the catalytic dyad region of BACE1 through molecular docking studies. Interestingly, the 200 ns molecular dynamics simulation study further confirmed the stability of the complexes formed between 9 compounds and the BACE1 protein. Furthermore, the free energy calculations also revealed these complexes possess favorable energies. Astilbin, Delphinidin 3-glucoside, and kaempferol 7-O-glucoside showed good binding affinity and structural stability when compared to other compounds and the control CNP520. Following a preliminary screening, the Astilbin compound was chosen based on the grounds of binding affinity, ADMET Properties, Hbond formation, Molecular Dynamic simulation, and MM-PBSA studies. A subsequent 1microsecond molecular dynamics simulation was conducted for the Astilbin complex. Through microsecond simulation, it was found that Astilbin alters BACE1's behavior and induces conformational rearrangements. Thus, this study opens a gateway to inhibit the activity of BACE1 protein through Astilbin thereby disclosing the possibility of managing Alzheimer's Disease.