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J Mol Biol. 2016 Aug 11. pii: S0022-2836(16)30302-3. doi: 10.1016/j.jmb.2016.08.007. [Epub ahead of print]
Mapping the Resistance Potential of Influenza's H+ Channel Against an Antiviral Blocker.
Assa D1, Alhadeff R1, Krugliak M1, Arkin IT1.
Author information
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, that 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.
Copyright ? 2016. Published by Elsevier Ltd.
KEYWORDS:
Influenza; antiviral; channel blocker; drug resistance
PMID: 27524470 DOI: 10.1016/j.jmb.2016.08.007
[PubMed - as supplied by publisher]
Mapping the Resistance Potential of Influenza's H+ Channel Against an Antiviral Blocker.
Assa D1, Alhadeff R1, Krugliak M1, Arkin IT1.
Author information
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, that 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.
Copyright ? 2016. Published by Elsevier Ltd.
KEYWORDS:
Influenza; antiviral; channel blocker; drug resistance
PMID: 27524470 DOI: 10.1016/j.jmb.2016.08.007
[PubMed - as supplied by publisher]