Abstract

Objective: To find the neuraminidase H1N1 inhibition potential of 4-hydroxypanduratin A and its derivatives along with associated binding mechanism through virtual screening and molecular docking. Methods: Initially, the structural templates for neuraminidase proteins were identified from structural database using homology search and performed homology and ab initio modeling to predict native 3D structure using Modeller 9.10 and I-TASSER server, respectively. The reliability of the three-dimensional models was validated using Ramachandran plot. The molecular docking was performed using Autodcok 4.2 and molecular interactions were analyzed through PyMol, Chimera and LigPlot. Results: The neuraminidase protein sequences of ADH29478, ADD85918, AEM62864 (2009) and AFO38701 (2011 ) from India were modeled and validated. 4-hydroxypanduratin A and its 88 derivatives were docked in to active binding pockets of neuraminidase. The guanidine group of residues Arg152 and Trp179 of ADH29478 (Chennai) and AFO38701 (Gwalior) neuraminidase models present in the hydrophilic domain (-OH and =O groups) was found to have molecular interactions with high binding affinities of -7.40 kcal/mol and -8.66 kcal/mol, respectively to 1-(2,4-dihydroxyphenyl)-3,3-diphenylpropan-1-one (CID: 19875815) than other FDA approved drugs such as oseltamivir, zana-mivir, and peramivir. Conclusions: 1-(2,4-dihydroxyphenyl)-3,3-diphenylpropan-1-one will be a breakthrough for further drug development against swine flu.

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