1.4  Most coronaviruses have “receptor destroying activity”
While it is binding of viruses to sialic acid glycan that is of interest here, it should be kept in mind that it is often associated with a catalytic activity in which the sialic acid glycan is the substrate. In influenza these two aspects are particularly distinct by being on separate surface proteins, the hemagglutinin and neuraminidase respectively, but that separation is not true of all viruses. Not surprisingly, as noted above, most coronaviruses of the coronaviridae family also have capabilities to bind to sialic acid glycans, but they also have the ability to cleave the glycans, which is often described by authors as a “receptor destroying activity”. Like influenza C viruses, purified bovine coronavirus preparations have an esterase activity which inactivates O-acetylsialic acid-containing receptors on erythrocytes; diisopropyl fluorophosphate completely inhibited this receptor-destroying activity suggesting that the viral enzyme is in this case a serine esterase [8]. This is believed to facilitate the spread of virus infection by removing receptor determinants from the surface of infected cells (see discussion below) and prevent the formation of virus aggregates. Another coronavirus, porcine transmissible gastroenteritis virus (TGEV) recognizes N-glycolylneuraminic acid. Nor does it depend on the sialic acid binding activity for infection of cultured cells, but interaction with sialoglycoconjugates appears to help the virus to pass through the sialic acid-rich mucus layer in the epithelium of the small intestine. Hemagglutinin-esterases are a family of viral envelope glycoproteins that mediate reversible attachment to O-acetylated sialic acids. These too are said to be receptor-destroying, but the enzymic activity reaction is in this case not a cleavage in the sense used concerning neuraminidase, but rather a change in molecular recognition by removal from of the acetyl group from the C9 position of the above acetylated neuraminic acid residues. The other and probably major reason for researchers thinking of these actions as “receptor destroying” is because the picture is a little more complex than just allowing entry and exit from the host cell. Because many viruses attain host cell specificity by being selective for particular types of sialic acid, these may occur as decoys to the virus on off-target host cells and on free molecules in the extracellular environment. To prevent irreversible binding to these decoys, many viruses including many coronaviruses have receptor-destroying enzymes that are therefore interesting targets for antiviral intervention, exemplified by the influenza A virus neuraminidase [9].