Neprilysin inhibitor from herbal compounds as the latest adjuvant treatment of chronic heart failure

Abstract

Abstract Neprilysin (NEP) is an endopeptidase that metabolizes vasoactive peptides such as natriuretic peptides. Angiotensin Receptor-Neprilysin Inhibitor (ARNI) is an alternative therapy for chronic heart failure (CHF) which is better than angiotensin receptor antagonist therapy alone. This study aimed to identify herbal compounds as in silico NEP inhibitor for adjuvant treatment of CHF. In this study, structure of NEP was obtained from Protein Data Bank (5JMY) and sacubitril as a standard ligand was obtained from PubChem database (9811834). Indonesian herbal compounds were derived from the HerbalDB database that met criteria of Lipinski’s rule. Binding affinity and sites were determined using the AutoDock Vina software. Interaction of herbal compounds and NEP were visualized using the PyMol software. Indonesian herbal compounds with the same binding site at Arg102 dan Arg110 amino acids with sacubitril (-6.73 ± 0.06 Kcal/mol) was NSC9324 (-7.07 ± 0.05 Kcal/mol). From 517 herbal compounds, NSC93241 had similar conformation to the standard ligand. NSC93241 has similar molecular formula and molecular weight to herbal plant (Ruscus aculeatus Linn or Butcher’s broom). NSC93241 potentially becomes an NEP inhibitor in silico for adjuvant treatment of CHF. Further investigation is required for evaluation of the antagonist effect of this compound towards NEP.