Deep mutational scanning of EV-D68 3D RNA-dependent RNA-polymerase

Authors

• BA Catching
• PT Dolan

Abstract

Enterovirus D68 (EV-D68) is a respiratory pathogen of clinical significance. Despite a decade of search for antivirals against EV-D68, there are not any compounds that have successfully passed clinical trials. The virus may also mutate to the antiviral’s effect and render the antiviral ineffective. Deep mutational scanning (DMS) offers a method for both examining which regions of important viral genes are genetically robust or brittle and which mutations may overcome antiviral selection. In this study, we applied DMS to the EV-D68 3D-RNA-dependent RNA-polymerase, which both serves as an important potential antiviral target and as the source of the high mutation rate. Ribavirin was also selected
against, which provides a list of potential fidelity-associated mutants, which may be useful for the design of antivirals that target replication speed and fidelity. We present here a thorough analysis of this selection method that reveals biophysical and phenotypic constraints.

Scientific Focus Area: Virology

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