y neutralization and inform therapeutic strategies to inhibit viral infection. Graphical Abstract Highlights • Site-specific N-linked microheterogeneity is defined at 22 sites of SARS-CoV-2 Spike • Six sites of N-linked microheterogeneity of human ACE2 receptor are described • Molecular dynamics simulations of Spike and ACE2 show essential roles for glycosylation • We uncover roles for variants in prote