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International Journal of Zoology and Applied Biosciences Research Article
In-silico virtual screening of probable human γ-secretase inhibitors as attractive therapeutics in Alzheimer’s disease (AD)
Subhasree Panigrahy, Koushik Sarker, Purna Nagasree Kurre , Baratam Sandhya Rani and Konna Balakrishna
Year : 2025 | Pages: 687-696
Received on: 14/10/2025
Revised on: 27/10/2025
Accepted on: 22/11/2025
Published on: 01/12/2025
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Subhasree Panigrahy, Koushik Sarker, Purna Nagasree Kurre , Baratam Sandhya Rani and Konna Balakrishna( 2025).
In-silico virtual screening of probable human γ-secretase inhibitors as attractive therapeutics in Alzheimer’s disease (AD)
. International Journal of Zoology and Applied Biosciences, 10( 6), 687-696.
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Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative condition with two distinct neuropathological features. i.e, Extracellular amyloid plaque depositions & intracellular neurofibrillary tangles. AD is a neurological disorder that mainly affects memory but may also impair other cognitive functions. The inability to remember recent events is an early symptom of Alzheimer's disease. Reductions of Aβ-level with the help of γ-secretase inhibitor (GSI) could slow down the progression of alzheimer's disease. Molecular docking study of gamma secretase inhibitors (PDB accession code: 6LQG) was performed using CDOCKER protocol in reference with Avagacestat. In total 61, 95, 989 compounds were collected from different databases [Asinex BioDesign library (1,70,269), Asinex Elite library (91,001), Enamine HTS collection (21,02,303), Maybridge HitCreator_V2 (39,197), Zinc15 (40,013), BIONET key organics complete collection (2,05,137) Chemspace Lead-like compounds (12,08,582), FCH group screening libraries (22,44,487), and OTAVA (95,000)] & screened against the target protein human γ-secretase. Out of them four best HITs were identified as Hit-1/Code 14355, Hit-2/Code 15656, Hit-3/Code 46593, Hit-4/Code 52641. The present study revealed that all the Hit compounds have a higher dock score (-53.222, -96.086, -107.279, -134.855 Kcal/mol respectively) than the reference compound (- 26.295 Kcal/mol) and better binding affinities (93.44, 78.78, 101.65, 106.74) than the reference compound (76.71). Hit-4 has the highest dock score and high binding affinity. Based upon our observations using in silico analysis, hit compounds can be utilize in the management of Alzheimer’s disease as potent gamma secretase inhibitors.
Keywords
Alzheimer's disease, BIOVIA, Gamma secretase inhibitors, Molecular docking.
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© The Author(s) 2025. This article is published by International Journal of Zoology and Applied Biosciences under the terms of the Creative Commons Attribution 4.0 International License (creativecommons.org), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
