Neuraminidase inhibitors rewire neutrophil function in murine sepsis and COVID-19 patient cells.

ABSTRACT: Neutrophils overstimulation plays a crucial role in tissue damage during severe infections. Neuraminidase-mediated cleavage of surface sialic acid has been demonstrated to regulate leukocyte responses. Here, we report that antiviral neuraminidase inhibitors constrain host neuraminidase activity, surface sialic acid release, ROS production, and NETs released by microbial-activated human neutrophils. In vivo , treatment with Oseltamivir results in infection control and host survival in murine models of sepsis. Moreover, Oseltamivir or Zanamivir treatment of whole blood cells from severe COVID-19 patients reduces host NEU-mediated shedding of surface sialic acid and neutrophil overactivation. These findings suggest that neuraminidase inhibitors are host-directed interventions to dampen neutrophil dysfunction in severe infections.

SUBMITTER: Formiga RO 

PROVIDER: S-EPMC7668734 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature