Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Nov;70(11):2470-2484.
doi: 10.1111/evo.13041. Epub 2016 Sep 13.

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

Claudia Bank  1   2   3 , Nicholas Renzette  4 , Ping Liu  5 , Sebastian Matuszewski  1   2 , Hyunjin Shim  1   2 , Matthieu Foll  1   2   6 , Daniel N A Bolon  7 , Konstantin B Zeldovich  8 , Timothy F Kowalik  4 , Robert W Finberg  5 , Jennifer P Wang  9 , Jeffrey D Jensen  10   11   12
Affiliations

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

Claudia Bank et al. Evolution. 2016 Nov.

Abstract

The rapid evolution of drug resistance remains a critical public health concern. The treatment of influenza A virus (IAV) has proven particularly challenging, due to the ability of the virus to develop resistance against current antivirals and vaccines. Here, we evaluate a novel antiviral drug therapy, favipiravir, for which the mechanism of action in IAV involves an interaction with the viral RNA-dependent RNA polymerase resulting in an effective increase in the viral mutation rate. We used an experimental evolution framework, combined with novel population genetic method development for inference from time-sampled data, to evaluate the effectiveness of favipiravir against IAV. Evaluating whole genome polymorphism data across 15 time points under multiple drug concentrations and in controls, we present the first evidence for the ability of IAV populations to effectively adapt to low concentrations of favipiravir. In contrast, under high concentrations, we observe population extinction, indicative of mutational meltdown. We discuss the observed dynamics with respect to the evolutionary forces at play and emphasize the utility of evolutionary theory to inform drug development.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types