Sialylation of host proteins as targetable risk factor for COVID‐19 susceptibility and spreading: A hypothesis

Bongiovanni, Antonella; Cusimano, Antonella; Annunziata, Ida; d’Azzo, Alessandra

Individuals infected with the severe acute respiratory syndrome (SARS)‐related coronavirus 2 (SARS‐CoV‐2) develop a critical and even fatal disease, called Coronavirus disease‐19 (COVID‐19), that eventually evolves into acute respiratory distress syndrome. The gravity of the SARS‐CoV‐2 pandemic, the escalating number of confirmed cases around the world, the many unknowns related to the virus mode of action, and the heterogenous outcome of COVID‐19 disease in the population ask for the rapid development of alternative approaches, including repurposing of existing drugs, that may dampen virus infectivity. SARS‐CoV‐2 infects human cells through interaction with sialylated receptors at the surface of epithelial cells, such as angiotensin‐converting enzyme 2 (ACE2). Glycan composition on virus entry receptors has been shown to influence the rate of infection of SARS‐CoV‐2 and spreading of virions has recently been linked to altered lysosomal exocytosis. These processes could concurrently involve the lysosomal system and its glycosidases. We hypothesize that modulating the activity of one of them, the lysosomal sialidase NEU1, could impinge on both the sialylation status of ACE2 and other host receptors as well as the extent of lysosomal exocytosis. Thus NEU1‐controlled pathways may represent therapeutic targets, which could impact on SARS‐CoV‐2 susceptibility, infectivity, and spread.