title: Identification of potential inhibitors of H5N1 influenza A virus neuraminidase by ligand-based virtual screening approach.
abstract: The neuraminidase (NA) of the influenza virus is the target of antiviral drug, oseltamivir. Recently, cases were reported that influenza virus becoming resistant to oseltamivir, necessitating the development of new long-acting antiviral compounds. In this report, a novel class of lead molecule with potential NA inhibitory activity was identified using a combination of virtual screening (VS), molecular docking, and molecular dynamic approach. The PubChem database was used to perform the VS analysis by employing oseltamivir as query. Subsequently, the data reduction was carried out by employing molecular docking study. Furthermore, the screened lead molecules were analyzed with respect to the Lipinski rule of five, drug-likeness, toxicity profiles, and other physico-chemical properties of drugs by suitable software program. Final screening was carried out by normal mode analysis and molecular dynamic simulation approach. The result indicates that CID 25145634, deuterium-enriched oseltamivir, become a promising lead compound and be effective in treating oseltamivir sensitive as well as resistant influenza virus strains.
authors.affiliation: Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India.
authors.forename: V
authors.initials: V
authors.lastname: Karthick
authors.forename: K
authors.initials: K
authors.lastname: Ramanathan
authors.forename: V
authors.initials: V
authors.lastname: Shanthi
authors.forename: R
authors.initials: R
authors.lastname: Rajasekaran
mesh_terms: D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D001682:Biological Availability; D055598:Chemical Phenomena; D062313:Databases, Pharmaceutical; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects* / Q000201:enzymology*; D008024:Ligands; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D014584:User-Computer Interface
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D008024:Ligands; D009439:Neuraminidase