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In silico study of inhibitory capacity of sacubitril/valsartan toward neprilysin and angiotensin receptor

Heart failure (HF) is a life-threatening condition that occurs when the heart cannot pump enough blood and oxygen to meet the body's needs. It affects mostly the elderly, commonly from the male population, especially those with obesity, diabetes, or some other chronic condition. It can be treat...

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Autores principales: Jovanović, Jelena Đorović, Antonijević, Marko, Vojinović, Radiša, Filipović, Nenad D., Marković, Zoran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9575392/
https://www.ncbi.nlm.nih.gov/pubmed/36321085
http://dx.doi.org/10.1039/d2ra04226f
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author Jovanović, Jelena Đorović
Antonijević, Marko
Vojinović, Radiša
Filipović, Nenad D.
Marković, Zoran
author_facet Jovanović, Jelena Đorović
Antonijević, Marko
Vojinović, Radiša
Filipović, Nenad D.
Marković, Zoran
author_sort Jovanović, Jelena Đorović
collection PubMed
description Heart failure (HF) is a life-threatening condition that occurs when the heart cannot pump enough blood and oxygen to meet the body's needs. It affects mostly the elderly, commonly from the male population, especially those with obesity, diabetes, or some other chronic condition. It can be treated with different medications, and promising results were shown by a relatively new medicament called Entresto. Results obtained from molecular docking and molecular dynamics simulations to examine the inhibitory capacity of Entresto are presented in this study. Parameters obtained by the molecular docking simulations show that both parts of Entresto (sacubitril (SAC) and valsartan (VAL)) interact with targeted proteins, and inhibit their physiological function. Simulations of molecular dynamics revealed some interesting inhibitory patterns. SAC was discovered to produce structural alterations in neprilysin by binding to it, reducing neprilysin's physiological activity. In addition to blocking the active site, SAC binding causes the enzyme's structure to become less compact over time, causing changes in its biochemical characteristics and preventing the enzyme from performing its biological function. Similar to SAC, VAL also causes deviations in the structure of angiotensin receptors. The angiotensin receptor GPCR (G-protein-coupled receptors) is immersed in the lipid bilayer, and changes in the tertiary structure are only visible through RMSD and RMSF, not by examining R(g). In this regard, MD simulations validated the results of molecular docking simulations, demonstrating that both SAC and VAL had inhibitory potential towards the neprilysin and angiotensin receptors, respectively.
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spelling pubmed-95753922022-10-31 In silico study of inhibitory capacity of sacubitril/valsartan toward neprilysin and angiotensin receptor Jovanović, Jelena Đorović Antonijević, Marko Vojinović, Radiša Filipović, Nenad D. Marković, Zoran RSC Adv Chemistry Heart failure (HF) is a life-threatening condition that occurs when the heart cannot pump enough blood and oxygen to meet the body's needs. It affects mostly the elderly, commonly from the male population, especially those with obesity, diabetes, or some other chronic condition. It can be treated with different medications, and promising results were shown by a relatively new medicament called Entresto. Results obtained from molecular docking and molecular dynamics simulations to examine the inhibitory capacity of Entresto are presented in this study. Parameters obtained by the molecular docking simulations show that both parts of Entresto (sacubitril (SAC) and valsartan (VAL)) interact with targeted proteins, and inhibit their physiological function. Simulations of molecular dynamics revealed some interesting inhibitory patterns. SAC was discovered to produce structural alterations in neprilysin by binding to it, reducing neprilysin's physiological activity. In addition to blocking the active site, SAC binding causes the enzyme's structure to become less compact over time, causing changes in its biochemical characteristics and preventing the enzyme from performing its biological function. Similar to SAC, VAL also causes deviations in the structure of angiotensin receptors. The angiotensin receptor GPCR (G-protein-coupled receptors) is immersed in the lipid bilayer, and changes in the tertiary structure are only visible through RMSD and RMSF, not by examining R(g). In this regard, MD simulations validated the results of molecular docking simulations, demonstrating that both SAC and VAL had inhibitory potential towards the neprilysin and angiotensin receptors, respectively. The Royal Society of Chemistry 2022-10-17 /pmc/articles/PMC9575392/ /pubmed/36321085 http://dx.doi.org/10.1039/d2ra04226f Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Jovanović, Jelena Đorović
Antonijević, Marko
Vojinović, Radiša
Filipović, Nenad D.
Marković, Zoran
In silico study of inhibitory capacity of sacubitril/valsartan toward neprilysin and angiotensin receptor
title In silico study of inhibitory capacity of sacubitril/valsartan toward neprilysin and angiotensin receptor
title_full In silico study of inhibitory capacity of sacubitril/valsartan toward neprilysin and angiotensin receptor
title_fullStr In silico study of inhibitory capacity of sacubitril/valsartan toward neprilysin and angiotensin receptor
title_full_unstemmed In silico study of inhibitory capacity of sacubitril/valsartan toward neprilysin and angiotensin receptor
title_short In silico study of inhibitory capacity of sacubitril/valsartan toward neprilysin and angiotensin receptor
title_sort in silico study of inhibitory capacity of sacubitril/valsartan toward neprilysin and angiotensin receptor
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9575392/
https://www.ncbi.nlm.nih.gov/pubmed/36321085
http://dx.doi.org/10.1039/d2ra04226f
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