Passaging of an influenza A(H1N1)pdm09 virus in a difluoro sialic acid inhibitor selects for a novel, but unfit I106M neuraminidase mutant
Jennifer L McKimm-Breschkin, Susan Barrett, Charley McKenzie-Kludas, Julie McAuley, Victor A Streltsov, Stephen G Withers
Antiviral Research | ELSEVIER | Published : 2019
An influenza A(H1N1)pdm09 and an influenza B virus were passaged in 3-fluoro(eq)-4-guanidino difluoro sialic acid (3Feq4Gu DFSA), an inhibitor of the influenza neuraminidase (NA) to determine whether resistant variants could be selected. 3Feq4Gu DFSA is a mechanism-based inhibitor, forming a covalent link to Y406 in the NA active site. Given its similarity to the natural substrate, sialic acid, we predicted resistant variants would be difficult to select. Yields of both viruses decreased with passaging, so that after 12 passages both viruses were only growing to low titers. Drug concentrations were decreased for another three passages. There was no difference in NA sensitivity in the MUNANA ..View full abstract
We thank Dr Richard Liggins and his colleagues at the Centre for Drug Research and Development (CDRD) for valuable discussions. We thank the Canadian Institutes for Health Research, Genome BC and CDRD for financial assistance.