Bryson Hammer, University of Alberta

Egor P Tchesnokov (1), Dana Kocincova (1), Oluwafemi Adu (1), Matthias Götte(1) - (1) Department of Medical Microbiology and Immunology, College of Medicine and Dentistry, University of Alberta

Fighting & Responding

Influenza viruses pose a significant burden on human life and remain a persistent threat to public health globally. In outbreak situations, antivirals can be used to treat and to prevent severe disease. However, the intrinsic genetic variability of influenza viruses can reduce the efficacy of vaccines and antiviral drugs. It is therefore important to assess drug susceptibility across subtypes and strains. Here, we focus on influenza A neuraminidase (NA) as a target for the approved antiviral drugs oseltamivir, zanamivir, and peramivir. NA is the primary glycoprotein responsible for release from infected cells, and these compounds inhibit this process through active site binding. We directly compare the efficacy of NA inhibitors in biochemical assays against purified, recombinant NA. The relevant influenza strains include influenza A H5N1 and H5N5 from recently infected individuals in British Columbia (BC) and Washington, respectively. We developed a method that allows accurate comparison of NA activities from prototypic and emerging viruses with and without known resistance conferring mutations, e.g. H275Y. We demonstrate that NA from highly pathogenic avian influenza A (H5N1, clade 2.3.4.4b, BC/Canada) is efficiently inhibited with all three approved antiviral drugs. However, measurements of half maximal inhibitory concentrations (IC50s) reveal important differences within and across subtypes. The results of this study provide a rapid tool for the evaluation of drug efficacies against emerging influenza viruses that require attention.