Virtual High Throughput Screening of Marine Bacterial Metabolites for BACE1 Inhibition

Annu Grewal , Deepak Sheokand , Raveena Chauhan , Vandana Saini and Ajit Kumar^*

Toxicology and Computational Biology Group, Centre for Bioinformatics, Maharshi Dayanand University, Rohtak, Haryana, India.

Corresponding Author E-mail: akumar.cbt.mdu@gmail.com

ABSTRACT: Alzheimer's disease is a neurodegenerative ailment reportedly caused by abnormal production or collection of amyloid-β peptides. Alzheimer-causing Aβ peptides are produced when amyloid precursor protein is cleaved by β-secretase-1 (BACE1). Previous failures in clinical trials of BACE1 inhibitors have invited studies with lesser side effects and better therapeutic efficacy. Marine bacterial metabolites have been used successfully as therapeutic options for many diseases and hence will be suitable to study for their potential as Alzheimer's disease therapeutics. The present work attempted to virtually screen marine bacterial metabolites by molecular docking studies against BACE1. A total of 2884 marine bacterial metabolites were retrieved from the Comprehensive Marine Natural Products Database and analyzed for drug-like properties, using Lipinski’s rules, ADMET profiling and binding affinities. Atabecestat was selected as the standard BACE1 inhibitor for our study. The initial screening using Lipinski’s rule selected 1357 compounds and further filtration using ADMET properties calculated 199 metabolites. Molecular docking studies against BACE1 resulted in 8 marine microbial metabolites echoside D (-9.9 kcal/mol), urdamycin N6 (-9.9 kcal/mol), echoside A (-9.7 kcal/mol), nocatrione A (-9.6 kcal/mol), nocatrione B (-9.5 kcal/mol), homoseongomycin (-9.4 kcal/mol), echoside B (-9.2 kcal/mol) and thioquinomycin A (-9.2 kcal/mol) having binding affinity higher than Atabecestat (-8.9kcal/mol).

KEYWORDS: Alzheimer’s Disease; BACE1; Marine Bacterial Compounds; Molecular Docking Studies

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