Structure-guided design of a novel class of benzyl-sulfonate inhibitors for influenza virus neuraminidase

Dimitris Platis , Brian J Smith , Trevor Huyton , Nikolaos E Labrou (1)

1 Agricultural Biotechnology

Influenza neuraminidase (NA) is an antiviral target of high pharmaceutical interest because of its essential role in cleaving sialic acid residues from cell surface glycoproteins and facilitating release of virions from infected cells. The present work describes the use of structural information in the progressive design from a lead binding ion, a sulphate, to a potent submicromolor inhibitor (K i} 0.13 {mu}M). Structural information derived from the X-ray structure of a NA complexed with several sulphate ions, in combination with data derived by affinity labelling and molecular modelling studies, was used to guide design of potent sulphonic acid-based inhibitors. These inhibitors are structural fragments of polysulphonate triazine dye Cibacron Blue 3GA (CB3GA), and represent novel lead scaffolds for designing non-carbohydrate inhibitors for influenza neuraminidases.

Mots clés: Life Sciences

Dimitris Platis, Brian J Smith, Trevor Huyton, Nikolaos E Labrou. Structure-guided design of a novel class of benzyl-sulfonate inhibitors for influenza virus neuraminidase. Biochemical Journal, 2006, 399 (2), pp.215-223. ⟨10.1042/BJ20060447⟩. ⟨hal-00478565⟩