title: Pharmacophore-Based Virtual Screening for Identification of Novel Neuraminidase Inhibitors and Verification of Inhibitory Activity by Molecular Docking.
abstract: 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.
authors.forename: Sidra
authors.initials: S
authors.lastname: Batool
authors.forename: Gohar
authors.initials: G
authors.lastname: Mushtaq
authors.forename: Warda
authors.initials: W
authors.lastname: Kamal
authors.affiliation: Metabolomics & Enzymology Unit, Fundamental and Applied Biology Group, King Fahd Medical Research Center, King Abdulaziz University, P. O. Box 80216, Jeddah 21589, Saudi Arabia. prof.makamal@lycos.com.
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Kamal
mesh_terms: D000146:Acids, Carbocyclic; D001665:Binding Sites; D003517:Cyclopentanes / Q000737:chemistry; D062126:Databases, Chemical; D065089:Glycoside Hydrolase Inhibitors / Q000737:chemistry*; D006146:Guanidines / Q000737:chemistry; D053124:Influenza A Virus, H5N1 Subtype / Q000201:enzymology; D008024:Ligands; D062105:Molecular Docking Simulation; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D053139:Oseltamivir / Q000737:chemistry; D011714:Pyrans; D012794:Sialic Acids; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D053243:Zanamivir / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: D000146:Acids, Carbocyclic; D003517:Cyclopentanes; D065089:Glycoside Hydrolase Inhibitors; D006146:Guanidines; D008024:Ligands; D011714:Pyrans; D012794:Sialic Acids; D014764:Viral Proteins; D053139:Oseltamivir; C546918:laninamivir; D009439:Neuraminidase; D053243:Zanamivir; C414210:peramivir