5.1. Evolutionary Origin and Classification of the CoV HE
Certain viruses use glycoproteins such as HA, HE, S and HEF for host receptor binding or destruction. Coronaviridae, Orthomyxoviridae, Paramyxoviridae and Adenoviridae utilize SAs as binding molecules for attachment and entry. However, only limited human pathogens recognize O-Ac SA.

5.1.1. Influenza Virus A and B Spike Proteins of HA and NA
Influenza A and B viruses bear two spikes of receptor-binding HA and NA [45].

5.1.2. Influenza C virus HA-HEF
HEF is indeed an ancient type of SA-O-acetylesterase. In contrast to A/B, the influenza C virus bears one spike with triple functions of HEF as a homotrimer [46]. Each HEF subunit bears two Neu5,9Ac2-binding sites and binds to the 9-O-acetyl group. In parallel, another modification of O-acetylation is found. Indeed, influenza C virus bears SA-O-acetylesterase [47], which converts 5-N-acetyl-9-O-NeuAc (Neu5,9Ac2) to 5-Neu5Ac. The 9-O-acetyl SA is a unique determinant for the influenza C virus receptor and Neu5,9Ac2 is crucial for receptor activity, but not Neu5Gc or Neu5Ac [48]. Neu5,9Ac2 is an essential determinant for influenza virus C type-specific host cell tropism. NAs cleave the α-ketosidic linkages to the D-Gal or GalNAc. SA-O-acetylesterases cleave different O-acetyl linkages (Figure 5). The OH-group of Tyr224 and the guanidino group of Arg236 interact with the CH3CO-carbonyl oxygen [49]. HEF SA-O-acetylesterase is found in several enveloped (+) ssRNA viruses of influenza C virus and also in certain CoVs and toroviruses [47]. The CoVs are different from the orthomyxoviruses, which hold a segmented (−) ssRNA genome and are instead evolutionary linked to the family Coronaviridae, order Nidovirales [45].

5.1.3. CoV SA-O-Acetylesterase HE
CoVs and toroviruses of the Coronaviridae family are specific for the O-Ac SA receptors. Their S and HE glycoproteins are similar to influenza C virus HEF. CoVs and all toroviruses bear HE gene form class I envelope membrane proteins of about 400 amino acid residues which bear 7 to 12 N-glycosylation sites [50]. HE multimer forms enter virions. Bovine CoV (BCoV) and HCoV-OC43, similar to influenza C virus, recognize Neu5,9Ac2 and bear SA-9-O-acetylesterase [8]. CoV HEs are all O-acetylesterases. The HE enzymes found in torovirus, CoV and influenza C virus are evolutionarily interspecies-mutated with about 30% homology by heterologous RNA recombination [51] and horizontal gene transfer. Therefore, viral HEs are diverse and widespread over evolution.