Abstract: Swine flu disease is an incurable degenerative and terminal disease. It is associated with Neuraminidase (NA), Hemoagglutinin (HA), and Matrix (M2) protein .3D structure of the one protein neuraminidase was generated using Homology modeling. Active compound of medicinal natural compound – EPICATECHIN GALLATE, MARCHANTIN, XYLOPINE were selected as these three natural compound of chemical structure of the active component of these natural compound were drawn docked with Epicatechin gallate, Marchantin , Xylopine Active component combinations. Known inhibitor taken from the literature docked, and docked at the binding site. Obtain molecule Epicatechin gallate, Xylopine, Marchantin have been given score of -174.3 kcal/mol, -148.5 kcal/mol, -131.4 kcal/mol. This is greater than known inhibitor. Zanamivir and Oseltamivir have been given score of -155.9 kcal/mol, and -132.7 kcal/mol molecules were employed for similarity search from zinc database. To the candidate molecules with drug likeness property can be considered for the test in vitro. And finally it can act as lead compound for the future development and optimization.