Neuraminidase activity provides a practical read-out for a high throughput influenza antiviral screening assay

Maryna C. Eichelberger, Arash Hassantoufighi, Meng Wu, Min Li

Research output: Contribution to journalArticle

Abstract

Background. The emergence of influenza strains that are resistant to commonly used antivirals has highlighted the need to develop new compounds that target viral gene products or host mechanisms that are essential for effective virus replication. Existing assays to identify potential antiviral compounds often use high throughput screening assays that target specific viral replication steps. To broaden the search for antivirals, cell-based replication assays can be performed, but these are often labor intensive and have limited throughput. Results. We have adapted a traditional virus neutralization assay to develop a practical, cell-based, high throughput screening assay. This assay uses viral neuraminidase (NA) as a read-out to quantify influenza replication, thereby offering an assay that is both rapid and sensitive. In addition to identification of inhibitors that target either viral or host factors, the assay allows simultaneous evaluation of drug toxicity. Antiviral activity was demonstrated for a number of known influenza inhibitors including amantadine that targets the M2 ion channel, zanamivir that targets NA, ribavirin that targets IMP dehydrogenase, and bis-indolyl maleimide that targets protein kinase A/C. Amantadine-resistant strains were identified by comparing IC 50with that of the wild-type virus. Conclusion. Antivirals with specificity for a broad range of targets are easily identified in an accelerated viral inhibition assay that uses NA as a read-out of replication. This assay is suitable for high throughput screening to identify potential antivirals or can be used to identify drug-resistant influenza strains.

Original languageEnglish (US)
Article number109
JournalVirology Journal
Volume5
DOIs
StatePublished - 2008

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Neuraminidase
Human Influenza
Antiviral Agents
High-Throughput Screening Assays
Amantadine
IMP Dehydrogenase
Zanamivir
Viruses
Ribavirin
Viral Proteins
Virus Replication
Cyclic AMP-Dependent Protein Kinases
Drug-Related Side Effects and Adverse Reactions
Ion Channels
Protein Kinase C
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Neuraminidase activity provides a practical read-out for a high throughput influenza antiviral screening assay. / Eichelberger, Maryna C.; Hassantoufighi, Arash; Wu, Meng; Li, Min.

In: Virology Journal, Vol. 5, 109, 2008.

Research output: Contribution to journalArticle

Eichelberger, Maryna C. ; Hassantoufighi, Arash ; Wu, Meng ; Li, Min. / Neuraminidase activity provides a practical read-out for a high throughput influenza antiviral screening assay. In: Virology Journal. 2008 ; Vol. 5.
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