Mapping the Resistance Potential of Influenza's H+ Channel against an Antiviral Blocker

Dror Assa, Raphael Alhadeff, Miriam Krugliak, Isaiah T. Arkin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

The development of drug resistance has long plagued our efforts to curtail viral infections in general and influenza in particular. The problem is particularly challenging since the exact mode of resistance may be difficult to predict, without waiting for untreatable strains to evolve. Herein, a different approach is taken. Using a novel genetic screen, we map the resistance options of influenza's M2 channel against its aminoadamantane antiviral inhibitors. In the process, we could identify clinically known resistant mutations in a completely unbiased manner. Additionally, novel mutations were obtained, which, while known to exist in circulating viruses, were not previously classified as drug resistant. Finally, we demonstrated the approach against an anti-influenza drug that has not seen clinical use, identifying several resistance mutations in the process. In conclusion, we present and employ a method to predict the resistance options of influenza's M2 channel to antiviral agents ahead of clinical use and without medical hazard.

Original languageAmerican English
Pages (from-to)4209-4217
Number of pages9
JournalJournal of Molecular Biology
Volume428
Issue number20
DOIs
StatePublished - 9 Oct 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Ltd

Keywords

  • antiviral
  • channel blocker
  • drug resistance
  • influenza

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