Neuraminidase inhibitors rewire neutrophil function in vivo in murine sepsis and ex vivo in COVID-19.
Rodrigo de Oliveira FormigaFlávia C AmaralCamila F SouzaDaniel A G B MendesCarlos Wagner S WanderleyCristina B LorenziniAdara A Dos SantosJuliana AntôniaLucas F FariaCaio C NataleNicholas M PaulaPriscila C S SilvaFernanda Rodrigues FonsecaLuan AiresNicoli HeckMárick R StarickShana Priscila Coutinho BarrosoAlexandre MorrotJohan Van WeyenberghRegina SordiFrederico Alisson-SilvaDaniel Santos MansurFernando de Queiroz CunhaEdroaldo Lummertz da RochaVéronique Witko-SarsatPierre Regis BurgelClémance MartinRosemeri Maurici da SilvaAndré BáficaMatthew Scott MacauleyFernando SpillerPublished in: bioRxiv : the preprint server for biology (2021)
In a severe systemic inflammatory response, such as sepsis and COVID-19, neutrophils play a central role in organ damage. Thus, finding new ways to inhibit the exacerbated response of these cells is greatly needed. Here, we demonstrate that in vitro treatment of whole blood with the viral neuraminidase inhibitors Oseltamivir or Zanamivir, inhibits the activity of human neuraminidases as well as the exacerbated response of neutrophils. In experimental models of severe sepsis, oseltamivir decreased neutrophil activation and increased the survival rate of mice. Moreover, Oseltamivir or Zanamivir ex vivo treatment of whole blood cells from severe COVID-19 patients rewire neutrophil function.