Oseltamivir and Zanamivir are two of the recently licensed neuraminidase inhibitors used
for the treatment of influenza. However, alternative antiviral agents are needed due to the development
of resistant mutations in Oseltamivir subtype H1N1 and H5N1 avian influenza A viruses, the latter being
a highly pathogenic avian virus that can be transferred to humans upon immediate contact with H5N1 infected poultry
or surface. Novel drug inhibiting group 1 neuraminidases may potentially be developed through addition of extra substituent
moieties to existing inhibitor skeletons. Another approach involves virtual screening of existing inhibitor skeletons
which we have reported using novel ligands of H5N1 via virtual screening approach. In this study, we have used 3D structure
of avian influenza virus H5N1 neuraminidase as target against a ligand dataset of four known neuraminidase inhibitors
for in silico analysis. Using the dataset of known four inhibitors, a pharmacophore model was developed using
ligand-based pharmacophore modeling strategy. This pharmacophore model was then used for virtual screening of natural
compounds library taken from Princeton database. New hits that shared features of our pharmacophore model and binding
interactions with receptor residues have been reported in this study. As more antiviral agents are required, the reported
hits in our study may play an important role as novel antiviral agents against influenza virus.
Keywords: Neuraminidase inhibitors, virtual screening, pharmacophore model, antiviral agents.
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