A screening assay for neuraminidase inhibitors using neuraminidases N1 and N3 from a baculovirus expression system

J Enzyme Inhib Med Chem. 2012 Feb;27(1):5-11. doi: 10.3109/14756366.2011.568415. Epub 2011 Jul 8.

Abstract

Context: Development of inexpensive and safe enzymatic assays to screen for putative neuraminidase inhibitors.

Objective: Validate the use of recombinant neuraminidase expressed in baculovirus located on the viral surface capsule to develop a neuraminidase inhibitor screening assay.

Materials and methods: Recombinant baculovirus particles displaying neuraminidase N1 and N3 were used as enzyme sources. The assay set-up required the use of 2'-(4-methylumbelliferyl)-α-D-acetyl neuraminic acid as substrate and oseltamivir carboxylate as benchmark inhibitor.

Results: The assay was set up in a standard 96-well plate. The within- and between-assay coefficients of variation were, on average, less than 10%. The 50% inhibitory concentration values of the inhibitor were in good agreement with those determined by independent kinetic experiments.

Discussion and conclusions: The assay showed satisfactory within- and between-assay repeatability. The obtained results suggest that recombinant baculovirus expressing neuraminidase located on the virus membrane capsule can be used to set up affordable and reliable neuraminidase inhibitors screening assays.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Baculoviridae / genetics*
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Influenza A Virus, H7N1 Subtype / enzymology*
  • Influenza A Virus, H7N1 Subtype / genetics
  • Influenza A Virus, H7N3 Subtype / enzymology*
  • Influenza A Virus, H7N3 Subtype / genetics
  • Kinetics
  • Neuraminidase / antagonists & inhibitors*
  • Neuraminidase / metabolism
  • Oseltamivir / analogs & derivatives*
  • Oseltamivir / chemistry
  • Oseltamivir / pharmacology
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Oseltamivir
  • Neuraminidase
  • oseltamivir carboxylate