Development of New Neprilysin Inhibitor as a Modulator of Chronic Kidney and Heart Disease Using In Silico Drug Repurposing Approach

The pathophysiology of chronic heart and kidney disease is interlinked and associated with different signalling pathways. The global burden of chronic kidney and heart diseases are increasing rapidly due to different interlinked factors. An increased risk of kidney diseases was observed in heart failure patients. Similarly, chronic kidney disease-induced a disturbance in homeostasis may directly affect cardiovascular disease by increasing blood pressure. These similarities in the pathogenesis of chronic kidney and heart disease, have led to the hypothesis that treatments proven for heart failure can be used as a treatment for kidney diseases. Recently in 2015, US FDA approved Sacubitril/Valsartan, the combination of Neprilysin (NEP) inhibitor (Sacubitril) and angiotensin receptor blocker (ARB) (Valsartan) for the treatment of heart failure with reduced ejection fraction. Further, in 2017, the combination of NEP inhibitor with ARB was also found to be more effective in renal failure patient as compared to ARB alone.