page_title: Discovery and development of neuraminidase inhibitors
section_title: Viral neuraminidase
hierarchical_section_title: Discovery and development of neuraminidase inhibitors / Development / Binding site / Viral neuraminidase
caption_attribution_description: English: Neu5Ac
context_page_description: Neuraminidase inhibitors inhibit enzymatic activity of the enzyme neuraminidase. These type of inhibitors have been introduced as anti-influenza drugs as they prevent the virus from exiting infected cells and thus stop further spreading of the virus. Neuraminidase inhibitors for human neuraminidase have the potential to be useful drugs as the enzyme plays a role in several signaling pathways in cells and is implicated in diseases such as diabetes and cancer.
context_section_description: Influenza virus neuraminidase (vNEU) consists of 4 co-planar roughly spherical subunits predominantly made of β-sheets, characterized as a 6-fold β-propeller and a hydrophobic region embedded in the virus’ membrane. The active site is located near the middle of the pseudo-symmetric sphere. Influenza virus neuraminidase only cleaves terminal Neu5Ac residues. X-ray crystallography has shown a distorted half-chair arrangement of the Neu5Ac substrate in the active site. This distorted structure forms a sialosyl cation after the release of the aglycon and is then trapped in the active site by a nucleophilic attack of the tyrosine residue. The orientation of the substrate in the active site is facilitated mainly by three strain-preserved Arginine residues binding the C1 acid group with salt bridges. Furthermore, the active site consists of eight other highly conserved amino acid-residues that make direct contact to the substrate or its derivatives. Including a glutamic acid residue binding the C7 and C9 alcohol groups on the glycerol side-chain (at C6) with hydrogen bonds and several hydrophobic residues correlating with the methyl group on the C5 N-acetyl and the hydrophobic backbone of the glycerol.
caption: Carbon-mapped N-acetylneuraminic acid (Neu5Ac)
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