Antiviral Methods and Protocols pp 383-406

Part of the Methods in Molecular Biology book series (MIMB, volume 1030)

Methods to Determine Mechanism of Action of Anti-influenza Inhibitors

  • Angela Luttick
  • Stephanie Hamilton
  • Simon P. Tucker
Protocol

Abstract

Mechanism of action studies can be used to demonstrate an inhibitor’s ability to specifically inhibit viral replication via a virus-specific or host cell target. A well-characterized mechanism of action is useful in evaluating potential off-target toxicities (e.g., a viral polymerase inhibitor may be assessed for inhibition of host polymerase) and in designing studies to monitor the development of resistance. Several methods can be used to elucidate the mechanism of action of an anti-influenza inhibitor. The first group of methods establishes that the activity of an inhibitor occurs at concentrations that do not cause cytotoxicity, investigates the selective inhibition of influenza, and indicates that inhibition is virus specific in nature. The second group of methods establishes the site of action, typically a target protein, and includes genotypic and phenotypic analysis of variants selected under inhibitor pressure. Finally, methods for measuring virion associated activities and their inhibition are described.

Key words

Antiviral Cytotherapeutic index Influenza virus Mechanism of action Multiplicity of infection Neuraminidase inhibition Polymerase Selection of resistant variants Time of addition 

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Copyright information

© Springer Science+Business Media, LLC 2013

Authors and Affiliations

  • Angela Luttick
    • 1
  • Stephanie Hamilton
    • 1
  • Simon P. Tucker
    • 1
  1. 1.Biota Pharmaceuticals, Inc.Notting HillAustralia

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