GS4071 is a slow-binding inhibitor of influenza neuraminidase from both A and B strains

Biochem Biophys Res Commun. 1998 Mar 17;244(2):408-13. doi: 10.1006/bbrc.1998.8282.

Abstract

The kinetics of inhibition of purified influenza neuraminidases from A/Tokyo/3/67 and B/Memphis/3/89 influenza viruses by (3R,4R,5S)-4-acetamido-5-amino-3-(1-ethylpropoxy)-1-cyclohexene- 1-carboxylic acid (GS4071) were investigated. Progress curve experiments established that GS4071 is a time dependent inhibitor of both A and B strains of influenza neuraminidase. The apparent association and dissociation rate constants, as well as the overall Ki values, were only modestly different for the two neuraminidase strains. The time dependent inhibition phenomenon, often referred to as slow-binding inhibition, appears to be a consequence of the very slow rate of dissociation of the compound from influenza neuraminidase.

Publication types

  • Comparative Study

MeSH terms

  • Acetamides / metabolism
  • Acetamides / pharmacology*
  • Binding Sites
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Hydrogen Bonding
  • Influenza A virus / drug effects*
  • Influenza A virus / enzymology*
  • Influenza B virus / drug effects*
  • Influenza B virus / enzymology*
  • Kinetics
  • Neuraminidase / antagonists & inhibitors*
  • Neuraminidase / chemistry
  • Oseltamivir
  • Protein Conformation
  • Species Specificity
  • Water

Substances

  • Acetamides
  • Enzyme Inhibitors
  • Water
  • Oseltamivir
  • Neuraminidase