1.2  Binding sialic acid glycans - a traditional picture from the influenza virus
The particular virus function that is considered in the present paper is non-covalent binding to the sialic acid glycans, i.e. oligosaccharides or polysaccharides that contain sialic acid residues. They are sometimes called sialylated glycans. Interest in this binding arose as follows. It seems unlikely (although of course possible) that functions important for many different kinds of virus are of little importance to others, especially if they have a common lifestyle such as infection of the respiratory system or alimentary tract, typically reflected by common symptoms. If such functions are absent, it begs the question of how the virus copes. Though glycan binding of SARS-CoV and SARS-CoV-2 seems absent, diminished, or relatively neglected in the literature (see Section 1.5), many coronaviruses such as human coronavirus OC43 and bovine coronavirus appear to recognize sialic acid as a receptor. However, most biology students are more familiar with the hemagglutinin and neuraminidase of influenza, the H and N in, for example H1N1 (the numbers such as 1 being based on immunological typing of these proteins), that bind to glycans, (sugar chains, oligosaccharides or polysaccharides) at cell surfaces notably those chemically bound to membrane proteins, hence called glycoproteins, of host cells. The surfaces of many animal and all vertebrate cells are dressed with a dense and complex array of glycans primarily containing sialic acids, attached to proteins and lipids at the cell surface. Such glycans also occur to a lesser extent in other organisms, ranging from fungi to yeasts and bacteria, and they are present at the surface of many viruses derived from animal hosts. Glycans can contain several kinds of sugar, including notably sialic acid, glucose, mannose, fucose, N-Acetylglucosamine, and N-Acetylgalactosamine. The standard emotive picture is that the influenza hemagglutinin binds the cell surface glycan molecules to first locate the lung cell surface, and that the neuraminidase has a later role, to enable many thousands (perhaps hundreds of thousands of) “baby viruses”, i.e. the newly formed virions, to cut their way out the protective layer of glycans when emerging from the cell. More correctly stated, when the replicated viruses bud from the host cells, they remain attached to the host-cell surface by binding between hemagglutinin and the “tips” of the glycan chains, and the neuraminidase is used to sever that link by breaking certain links between the component sugar residues (see below). Recent work has supported this long standing picture for influenza viruses, but also answers affirmatively to the question that must have arisen in many student's minds, i.e. that the neuraminidase must also be important for the virus to cut its way into the cell in the first place [7]. Any such description of entry does not, however, quite fit in with the above “more correctly stated” model for final release of the virion progeny, because it is not obvious why the incoming infecting virus should bind to the cell surface and then be made to disengage. Nonetheless, many viruses appear to need and do have an enzyme to achieve similar results, even if that enzyme is not of neuraminidase type and dissociates the virus from the cell in other ways: e.g. see Ref. [8] and discussion below. It does seem reasonable that all such similar results must provide assistance in the mobility of virus particles through the respiratory tract mucus, but a fuller picture should perhaps include the notion of “decoy” glycan molecules [9] as discussed below.