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

ABSTRACT: Influenza NA (neuraminidase) 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 paper describes the use of structural information in the progressive design from a lead binding ion (a sulfate) to a potent submicromolor inhibitor (K(i) 0.13 microM). Structural information derived from the X-ray structure of an NA complexed with several sulfate ions, in combination with results derived from affinity labelling and molecular modelling studies, was used to guide design of potent sulfonic acid-based inhibitors. These inhibitors are structural fragments of the polysulfonate triazine dye Cibacron Blue 3GA and represent novel lead scaffolds for designing non-carbohydrate inhibitors for influenza neuraminidases.

SUBMITTER: Platis D

PROVIDER: S-EPMC1609911 | biostudies-literature | 2006 Oct

REPOSITORIES: biostudies-literature

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

Platis Dimitris D Smith Brian J BJ Huyton Trevor T Labrou Nikolaos E NE

The Biochemical journal 20061001 2

Influenza NA (neuraminidase) 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 paper describes the use of structural information in the progressive design from a lead binding ion (a sulfate) to a potent submicromolor inhibitor (K(i) 0.13 microM). Structural information derived from the X-ray structure of an NA complexed with seve ...[more]

PMID: 16776653

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