Fig. 2: Ancestral relationships, functional domains and receptor specificity of viral envelope RBPs and RDEs involved in virus motility.

a The distribution of the indicated lectin, enzyme and fusion functions over different proteins is schematically depicted for each of the major virus groups that are discussed. HA, HEs and HEF share a common ancestry with an unknown “HEF-like” precursor (red letter) while the origin of other proteins (e.g. NA and HN) cannot be resolved on basis of primary sequence conservation. HEF, HA and isavirus HE¹¹⁶ form homotrimers, while corona- and torovirus HE are dimers⁴⁵. Remnant domains that are still recognizable but have lost function are marked by dashed-line/red letter. Note that the esterase function has been lost in HA while keeping a weak lectin function at what is called a vestigial esterase site (VES). The preferred receptor usage is indicated^116,117, but exceptions can occur. For instance, some murine CoVs display specificity for 4-O-acetylated Sia¹¹⁸. Created in BioRender. Liu, M. (2025) https://BioRender.com/kxmkvsn. b Relevant examples of structural modifications of Sias are shown. The Neu5Gc modification may abolish HA binding but does not occur in humans. O-acetylation also occurs on N- and O-glycans.