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