An experimental evaluation of drug-induced mutational meltdown as an antiviral treatment strategy

In this new paper in Evolution the authors study the evolutionary dynamics of influenza A virus under different concentrations of Favipiravir, which is a drug that leads to an increase in mutation rate across the genome. By tracking down real-time evolution of several populations they are able to evaluate the extinction dynamics and the potential adaptive response of the virus to different drug treatments.

With this setup the authors were able to show that:

1) Extinction occurs under high mutation rate – The virus populations under an increasing drug concentration show an increased mutation rate and number of mutations accumulated, resulting in rapid extinction and providing support for mutational meltdown as driving mechanism;

2) The virus populations may be able to adapt to intermediate drug conditions – Populations subjected to constant intermediate concentrations of Favipiravir showed indications of an adaptive viral response, suggesting that resistance may emerge under specific drug treatments;

3) Evolution of drug resistance can be explored by a combination of population genetic models and experimental evolution – The combination of population genetic models and experimental evolution is an excellent means to understand the evolutionary dynamics and genetics of virus resistance to drug treatments and to test the efficacy of new possible treatments.

 

 

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