Neuraminidase as a novel therapeutic management strategy for Alzheimer’s disease: evidenced through molecular docking, molecular dynamic simulation and gene expression analysis
IntroductionNeuraminidase in humans is studied to see how well repurposed oseltamivir works for treating Alzheimer’s disease (AD) using methods like molecular docking, molecular dynamic (MD) simulation, and gene expression analysis. Gene enrichment analysis was also studied to understand the behavio...
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Frontiers Media S.A.
2025-05-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2025.1574702/full |
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| author | Sami I. Alzarea Sami I. Alzarea Omar Awad Alsaidan Omar Awad Alsaidan Hassan H. Alhassan Abdulaziz Ibrahim Alzarea Tariq G. Alsahli Metab Alharbi Muhammad Afzal Mohammad Jaffar Sadiq Mantargi |
| author_facet | Sami I. Alzarea Sami I. Alzarea Omar Awad Alsaidan Omar Awad Alsaidan Hassan H. Alhassan Abdulaziz Ibrahim Alzarea Tariq G. Alsahli Metab Alharbi Muhammad Afzal Mohammad Jaffar Sadiq Mantargi |
| author_sort | Sami I. Alzarea |
| collection | DOAJ |
| description | IntroductionNeuraminidase in humans is studied to see how well repurposed oseltamivir works for treating Alzheimer’s disease (AD) using methods like molecular docking, molecular dynamic (MD) simulation, and gene expression analysis. Gene enrichment analysis was also studied to understand the behaviour of neuraminidases in humans.MethodsMolecular docking was done using oseltamivir and the neuraminidase proteins with the PyRx tool, and the results were analysed using BIOVIA Discovery Studio. MD simulation (50 ns) of the oseltamivir and neuraminidase complex was performed using GROMACS tools. The gene expression analysis and gene enrichment study were done using GEO2R, which showed the results as log FC and significant values. Enricher tool-based gene enrichment analysis was done to determine the gene behaviour related to the AD.ResultsThe molecular docking showed a strong connection between oseltamivir and neuraminidase (−6.5 kcal/mol), acetylcholinesterase (−7.9 kcal/mol), CDKs (−6.5 kcal/mol), and GSKs (−6.6 kcal/mol), interacting with different amino acids in the protein sequences. MD simulations showed a strong interaction between the ligand and neuraminidase, with stable measurements indicating that both the protein and ligand remained consistent in size and energy, which is better explained through the results of MM_PBSA and MM_GBSA analysis of the complex, resulting in the ΔE_vdW, ΔE_elec, ΔG_polar, ΔG_nonpolar, ΔG_gas, (ΔE_vdW + ΔEEL), ΔG_solvation: (ΔG_polar + ΔG_nonpolar) and ΔG_bind: total energies suggesting the complex stayed stable in conditions similar to those resembling natural cell. The gene expression analysis expressed TUBB3 (formation of beta-tubulin), FABP3 (regulates alpha-synuclein uptake in dopaminergic neurons), and CALM1 (calcium signal transduction pathway) to be highly upregulated in the given conditions with kinase binding (p = 0.0006541) and protein phosphatase regulatory activity (p = 0.001357) were highly upregulated, implicating their importance in the AD.DiscussionThe study ends on a hopeful note for using oseltamivir to treat neurological diseases, but it suggests that future research should include a solid cell line study, an in vitro study, and a clinical study. |
| format | Article |
| id | doaj-art-e9fc18de696543f283b6a21181c10407 |
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| publishDate | 2025-05-01 |
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| spelling | doaj-art-e9fc18de696543f283b6a21181c104072025-08-20T02:17:04ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462025-05-011310.3389/fchem.2025.15747021574702Neuraminidase as a novel therapeutic management strategy for Alzheimer’s disease: evidenced through molecular docking, molecular dynamic simulation and gene expression analysisSami I. Alzarea0Sami I. Alzarea1Omar Awad Alsaidan2Omar Awad Alsaidan3Hassan H. Alhassan4Abdulaziz Ibrahim Alzarea5Tariq G. Alsahli6Metab Alharbi7Muhammad Afzal8Mohammad Jaffar Sadiq Mantargi9Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka, Al-Jouf, Saudi ArabiaKing Salman Centre for Disability Research, Riyadh, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka, Al-Jouf, Saudi ArabiaKing Salman Centre for Disability Research, Riyadh, Saudi ArabiaDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Al-Jouf, Saudi ArabiaDepartment of Clinical Pharmacy, College of Pharmacy, Jouf University, Sakaka, Al-Jouf, Saudi ArabiaDepartment of Pharmacology, College of Pharmacy, Jouf University, Sakaka, Al-Jouf, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaDepartment of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, Jeddah, Saudi ArabiaDepartment of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, Jeddah, Saudi ArabiaIntroductionNeuraminidase in humans is studied to see how well repurposed oseltamivir works for treating Alzheimer’s disease (AD) using methods like molecular docking, molecular dynamic (MD) simulation, and gene expression analysis. Gene enrichment analysis was also studied to understand the behaviour of neuraminidases in humans.MethodsMolecular docking was done using oseltamivir and the neuraminidase proteins with the PyRx tool, and the results were analysed using BIOVIA Discovery Studio. MD simulation (50 ns) of the oseltamivir and neuraminidase complex was performed using GROMACS tools. The gene expression analysis and gene enrichment study were done using GEO2R, which showed the results as log FC and significant values. Enricher tool-based gene enrichment analysis was done to determine the gene behaviour related to the AD.ResultsThe molecular docking showed a strong connection between oseltamivir and neuraminidase (−6.5 kcal/mol), acetylcholinesterase (−7.9 kcal/mol), CDKs (−6.5 kcal/mol), and GSKs (−6.6 kcal/mol), interacting with different amino acids in the protein sequences. MD simulations showed a strong interaction between the ligand and neuraminidase, with stable measurements indicating that both the protein and ligand remained consistent in size and energy, which is better explained through the results of MM_PBSA and MM_GBSA analysis of the complex, resulting in the ΔE_vdW, ΔE_elec, ΔG_polar, ΔG_nonpolar, ΔG_gas, (ΔE_vdW + ΔEEL), ΔG_solvation: (ΔG_polar + ΔG_nonpolar) and ΔG_bind: total energies suggesting the complex stayed stable in conditions similar to those resembling natural cell. The gene expression analysis expressed TUBB3 (formation of beta-tubulin), FABP3 (regulates alpha-synuclein uptake in dopaminergic neurons), and CALM1 (calcium signal transduction pathway) to be highly upregulated in the given conditions with kinase binding (p = 0.0006541) and protein phosphatase regulatory activity (p = 0.001357) were highly upregulated, implicating their importance in the AD.DiscussionThe study ends on a hopeful note for using oseltamivir to treat neurological diseases, but it suggests that future research should include a solid cell line study, an in vitro study, and a clinical study.https://www.frontiersin.org/articles/10.3389/fchem.2025.1574702/fullAlzheimer’s diseaseoseltamivirneuraminidasemolecular dockingmolecular dynamic simulationgene expression analysis |
| spellingShingle | Sami I. Alzarea Sami I. Alzarea Omar Awad Alsaidan Omar Awad Alsaidan Hassan H. Alhassan Abdulaziz Ibrahim Alzarea Tariq G. Alsahli Metab Alharbi Muhammad Afzal Mohammad Jaffar Sadiq Mantargi Neuraminidase as a novel therapeutic management strategy for Alzheimer’s disease: evidenced through molecular docking, molecular dynamic simulation and gene expression analysis Frontiers in Chemistry Alzheimer’s disease oseltamivir neuraminidase molecular docking molecular dynamic simulation gene expression analysis |
| title | Neuraminidase as a novel therapeutic management strategy for Alzheimer’s disease: evidenced through molecular docking, molecular dynamic simulation and gene expression analysis |
| title_full | Neuraminidase as a novel therapeutic management strategy for Alzheimer’s disease: evidenced through molecular docking, molecular dynamic simulation and gene expression analysis |
| title_fullStr | Neuraminidase as a novel therapeutic management strategy for Alzheimer’s disease: evidenced through molecular docking, molecular dynamic simulation and gene expression analysis |
| title_full_unstemmed | Neuraminidase as a novel therapeutic management strategy for Alzheimer’s disease: evidenced through molecular docking, molecular dynamic simulation and gene expression analysis |
| title_short | Neuraminidase as a novel therapeutic management strategy for Alzheimer’s disease: evidenced through molecular docking, molecular dynamic simulation and gene expression analysis |
| title_sort | neuraminidase as a novel therapeutic management strategy for alzheimer s disease evidenced through molecular docking molecular dynamic simulation and gene expression analysis |
| topic | Alzheimer’s disease oseltamivir neuraminidase molecular docking molecular dynamic simulation gene expression analysis |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2025.1574702/full |
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