title: Inhibition of viral group-1 and group-2 neuraminidases by oseltamivir: A comparative structural analysis by the ScrewFit algorithm.
abstract: The viral surface glycoprotein neuraminidase (NA) allows the influenza virus penetration and the egress of virions. NAs are classified as A, B, and C. Type-A NAs from influenza virus are subdivided into two phylogenetically distinct families, group-1 and group-2. NA inhibition by oseltamivir represents a therapeutic approach against the avian influenza virus H5N1. Here, structural bases for oseltamivir recognition by group-1 NA1, NA8 and group-2 NA9 are highlighted by the ScrewFit algorithm for quantitative structure comparison. Oseltamivir binding to NA1 and NA8 affects the geometry of Glu119 and of regions Arg130-Ser160, Val240-Gly260, and Asp330-Glu382, leading to multiple NA conformations. Additionally, although NA1 and NA9 share almost the same oseltamivir-bound final conformation, they show some relevant differences as suggested by the ScrewFit algorithm. These results indicate that the design of new NA inhibitors should take into account these family-specific effects induced on the whole structure of NAs.
authors.affiliation: Centre de Biophysique Moléculaire, CNRS UPR, Orléans, France. paolo.calligari@ens.fr
authors.forename: Paolo A
authors.initials: PA
authors.lastname: Calligari
authors.forename: Gerald R
authors.initials: GR
authors.lastname: Kneller
authors.forename: Andrea
authors.initials: A
authors.lastname: Giansanti
authors.forename: Paolo
authors.initials: P
authors.lastname: Ascenzi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Porrello
authors.forename: Alessio
authors.initials: A
authors.lastname: Bocedi
mesh_terms: D000465:Algorithms; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D009980:Influenza A virus / Q000201:enzymology*; D008958:Models, Molecular; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D053139:Oseltamivir / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation
chemical_list: D004791:Enzyme Inhibitors; D010455:Peptides; D053139:Oseltamivir; D009439:Neuraminidase