Subtle Influence of ACE2 Glycan Processing on SARS-CoV-2 Recognition

The severity of SARS-CoV-2 infection is highly variable and yet the molecular basis for this effect remains elusive. One potential contribution are differences in glycosylation target human cells, particularly as has capacity to bind sialic acid which a common, variable, terminal modification glycans. viral spike glycoprotein (S) cellular receptor, angiotensin-converting enzyme 2 (ACE2) both densely glycosylated. We therefore sought investigate whether state ACE2 impacts interaction with spike. generated panel engineered glycoforms were analyzed by mass spectrometry reveal site-specific glycan modifications. then probed impact on S binding revealed subtle sensitivity hypersialylated or oligomannose-type glycans slightly impeding interaction. In contrast, deglycosylation did not influence binding. Overall, does significantly suggest that any role pathobiology will lie beyond its immediate receptor virus