Is that Possible to Design the Versatile Inhibitors for H1N1, H5N1, H5N2, and H5N7?

In this study, a QSAR model of neuraminidase (NA) type 1 (N1) was elevated. This map contained two hydrogen bond acceptor features, one hydrogen bond donor features, and one positive ionizable feature. In the second step, we created the interaction maps in the active sites on the neuraminidase type2, and type7 (N2 and N7) protein structures. The structure-based pharmacophore map was showed the features on every amino acid in the active site on the protein structure. The third step was pharmacophore comparison, root-mean-squared error (RMSE) was reported for the matching pharmacophore features. The result showed that the maps of N1, N2, and N7 had subtle differences in distances of each features. We created the combined map for N1, N2, and N7 to resolving the difference in the three NA types. The combined map was employed to NCI database screening, then, the potent versatile inhibitors were elevated in the results.

[1]  David J. Stevens,et al.  The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design , 2006, Nature.

[2]  Y. Kaneda,et al.  Development of a transferrin receptor-targeting HVJ-E vector. , 2007, Biochemical and biophysical research communications.

[3]  Stefano Costanzi,et al.  A virtual screen for diverse ligands: discovery of selective G protein-coupled receptor antagonists. , 2008, Journal of the American Chemical Society.

[4]  Osman Güner,et al.  Pharmacophore modeling and three dimensional database searching for drug design using catalyst: recent advances. , 2004, Current medicinal chemistry.

[5]  X. Y. Zhang,et al.  QSAR study of neuraminidase inhibitors based on heuristic method and radial basis function network. , 2008, European journal of medicinal chemistry.

[6]  Robyn Ayscue,et al.  Use of simple docking methods to screen a virtual library for heteroactivators of cytochrome P450 2C9. , 2007, Journal of medicinal chemistry.

[7]  V. D. da Silva,et al.  Use of virtual screening, flexible docking, and molecular interaction fields to design novel HMG-CoA reductase inhibitors for the treatment of hypercholesterolemia. , 2008, The journal of physical chemistry. A.

[8]  I. Bersuker,et al.  Improved Electron‐Conformational Method of Pharmacophore Identification and Bioactivity Prediction. Application to Angiotensin Converting Enzyme Inhibitors. , 2001 .

[9]  Alan J. Hay,et al.  Crystal structures of oseltamivir-resistant influenza virus neuraminidase mutants , 2008, Nature.

[10]  Isaac B. Bersuker,et al.  Improved Electron-Conformational Method of Pharmacophore Identification and Bioactivity Prediction. Application to Angiotensin Converting Enzyme Inhibitors , 2000, Journal of chemical information and computer sciences.

[11]  Y. Ikehara,et al.  Involvement of a host erythrocyte sialic acid content in Babesia bovis infection. , 2007, The Journal of veterinary medical science.

[12]  Alexander D. MacKerell,et al.  CHARMM force field parameters for simulation of reactive intermediates in native and thio‐substituted ribozymes , 2007, J. Comput. Chem..

[13]  L. Raymond,et al.  Treatment of post-influenza pneumonia in health care workers. , 2007, Journal of occupational and environmental medicine.

[14]  G. Vistoli,et al.  Fragmental Modeling of Human Glutamate Transporter EAAT1 and Analysis of its Binding Modes by Docking and Pharmacophore Mapping , 2008, ChemMedChem.

[15]  A. Saha,et al.  Pharmacophore mapping of arylbenzothiophene derivatives for MCF cell inhibition using classical and 3D space modeling approaches. , 2008, Journal of molecular graphics & modelling.

[16]  Jianguo Wu,et al.  Origin of highly pathogenic H5N1 avian influenza virus in China and genetic characterization of donor and recipient viruses. , 2007, The Journal of general virology.

[17]  Y. Kurogi,et al.  Discovery of novel mesangial cell proliferation inhibitors using a three-dimensional database searching method. , 2001, Journal of medicinal chemistry.

[18]  M. Moradi,et al.  Preparation of Neuraminidase-Specific Antiserum from the H9N2 Subtype of Avian Influenza Virus , 2007 .

[19]  Gerald H Lushington,et al.  A docking score function for estimating ligand-protein interactions: application to acetylcholinesterase inhibition. , 2004, Journal of medicinal chemistry.

[20]  Finn Drabløs,et al.  Protein Alpha Shape (PAS) Dock: A new gaussian-based score function suitable for docking in homology modelled protein structures , 2006, J. Comput. Aided Mol. Des..

[21]  I. Barr,et al.  Neuraminidase inhibitor drug susceptibility differs between influenza N1 and N2 neuraminidase following mutagenesis of two conserved residues. , 2007, Antiviral research.