1ivc
|
STRUCTURES OF AROMATIC INHIBITORS OF INFLUENZA VIRUS NEURAMINIDASE
OverviewOverview
Neuraminidase (NA), a surface glycoprotein of influenza virus, is a, potential target for design of antiinfluenza agents. The crystal structure, of influenza virus neuraminidase showed that in the active site 11, residues are universally conserved among all strains known so far. Several, potent inhibitors based on the carbohydrate compound, 2-deoxy-2,3-didehydro-D-N-acetylneuraminic acid (DANA) have been shown to, bind to the conserved active site and to reduce virus infection in animals, when administered by nasal spray. Inhibitors of this type are, however, rapidly excreted from physiological systems and may not be effective in, order to provide long-time protection. A new class of specific NA, inhibitors, which are benzoic acid derivatives, has been designed on the, basis of the three-dimensional structure of the NA-DANA complex and, modeling of derivatives of 4-(acetylamino)benzoic acid in the NA active, site. Intermediates were synthesized and were shown to moderately inhibit, the NA activity and to bind to the NA active site as predicted. These, rudimentary inhibitors, 4-(acetylamino)-3-hydroxy-5-nitrobenzoic acid, 4-(acetylamino)-3-hydroxy-5-aminobenzoic acid, and, 4-(acetylamino)-3-aminobenzoic acid, and their X-ray structures in, complexes with N2 (A/Tokyo/3/67) and B/Lee/40 neuraminidases have been, analyzed. The coordinates of such inhibitors complexed with NA were used, as the starting model for further design of more potent benzoic acid, inhibitors. Because the active site residues of NA are invariant, the, designed aromatic inhibitors have the potential to become an antiviral, drug against all strains of influenza virus.
About this StructureAbout this Structure
1IVC is a Single protein structure of sequence from [1] with CA and ST2 as ligands. Active as Exo-alpha-sialidase, with EC number 3.2.1.18 Full crystallographic information is available from OCA.
ReferenceReference
Structures of aromatic inhibitors of influenza virus neuraminidase., Jedrzejas MJ, Singh S, Brouillette WJ, Laver WG, Air GM, Luo M, Biochemistry. 1995 Mar 14;34(10):3144-51. PMID:7880809
Page seeded by OCA on Tue Nov 20 17:41:56 2007