Mary Hernando, University of Alberta

Mary Hernando1, Justine Beghin2, Kira Sviderskaia1, Mike Wong4, Sudip Subedi4, and Vanessa Meier-Stephenson1-3; 1 Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta; 2 Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta; 3 Li Ka Shing Institute of Virology, University of Alberta; 4 Advanced Cell Exploration Core, University of Alberta

Discovering & Evolving

Influenza viruses are an ongoing concern as seasonal epidemics strain the health care system. Additionally, the pandemic potential of these viruses necessitates dedicated research for novel methods to develop therapeutics. The Influenza virus encodes a conserved heterotrimeric viral RNA-dependent RNA polymerase (FluPol) that is essential to the proliferation of the virus. Replication and endonuclease activity are carried out by two different FluPol subunits. Here, the effects of ten DNA aptamers identified as strong binders via SELEX (Systematic Evolution of Ligands by EXponential enrichment) on the function of FluPol are examined; further, this demonstrates the applicability of SELEX for other important therapeutic targets. Aptamers are short oligonucleotides with distinct folds that may selectively bind to target binding sites. The effects of these individual aptamers on the endonuclease and replication functions of purified recombinant FluPol are measured using two fluorescent-based assays. Potential aptamer binding areas may be identified through comparing the effects of the aptamer on these FluPol functions. Aptamers with more selective disruption will be further characterized, with future work including structural insights (ex. cryo-EM) to identify novel binding sites that may be targeted for the development of pan-strain Influenza antivirals.