This study reports a biotechnological approach for the large-scale production of sialylated multivalent solid lipid microparticles (SSLMs) that can saturate hemagglutinins and prevent virus binding to host cells. This global approach combines a microbiological step leading to the production of sialylated maltodextrin chains by a metabolic engineered Escherichia coli strain, with a new in vitro enzymatic glycosylation method onto a long-chain alkyl glucoside, and the formulation of the final SSLMs presenting multivalent sialic acid.
Our results indicate that SSLMs have significant inhibition property against A/H1N1 pdm09 influenza virus in HI and MN in vitro assays. These results pave the way for further evaluation of SSLMs against several influenza A and B strains, we are already implementing, in order to characterize their putative broad-spectrum antiviral activity in preclinical in vitro and in vivo models of infection.
These results are issued from a very fruitful collaboration between the laboratory VirPath, Virnext and the Cermav. This work was supported by ANR (Agence nationale de la recherche), IDEX Université Grenoble Alpes, Labex ARCANE, GlycoAlps, CarnotPolyNat, SATT Linksium, Université Claude Bernard Lyon 1 EZUS LYON INGENIERIE PROJETS and the Région Auvergne-Rhône-Alpes.