2. The Cell Entry Mechanism of Encapsulated Viruses
Encapsulated viruses such as the SARS-CoV and SARS-CoV-2 viruses comprise of some general surface constituents. The surface envelope or capsule is presented as a lipid bilayer membrane that contains various envelope proteins (E), membrane proteins (M), and an outer layer that presents so-called spike (S) proteins [1]. M and S proteins are generally rich in sugar molecules that form a so-called glycan structure. N- or O-glycosylate moieties are commonly found in the viral S proteins and they can recognize some cell receptors to which the virion can bind [2,3]. These spike proteins facilitate virion entry into host cells. Encapsulated viruses such as the coronaviruses present approximately 200 of these spiky structures [4]. Spike proteins are comprised of glycoproteins, proteins that also contain polysaccharide or oligosaccharide moieties otherwise known as glycans [5,6,7].
The glycoproteins have a variety of functions that maintain the virion structure and properties such as water solubility, creation of diffusion barriers, and antiadhesive actions among others [6]. In addition to the intrinsic functions that glycoproteins afford to the maintenance of the virion structure, they also act as a structure that recognizes glycan-binding proteins presented on the membranes of potential host cells [1]. The viral glycans may be recognized by bacterial, fungal, and parasite-associated glycan-binding proteins. However, viruses are also recognized by host cells via the same mechanism. It is this form of intercellular recognition interactions that prove vital to effect the virus entry into host cells in which the virus could replicate [7].
A detailed description of the spike glycoproteins of SARS-CoV-2 reported that two binding subunits can be distinguished. These subunits become active when the two units are cleaved by host cell proteases on the host cell membrane. Subunit, S1 is responsible for binding to the host cell membrane and subunit, S2 is responsible for fusion of the virion and host cell membranes. The S1 unit is the factor that makes various coronaviruses specific toward a certain host [8]. Pulmonary angiotensin-converting-enzyme 2 (ACE-2) in humans exhibit the appropriate receptor, a specific sequence of amino acid residues [9], towards S1 and partly explains the effective spread of the coronaviruses via droplets in the atmosphere [10].
As part of the human host immune responses, the glycans of the coronavirus spike protein subunits are recognized by dendritic cells [11] in the blood which binds to the glycan and subsequently expresses CD4+ and CD8+ glycopeptides. These glycopeptides label the spike protein and this labeled protein is then presented to T-cells [12]. T-cells subsequently recognize the labels, phagocytose these antigen-marked viruses, and degrade them. It has been found that the glycan-binding proteins, also known as lectins [5], can impart broad-spectrum binding properties against HIV-1, SARS-CoV, and human cytomegalovirus. The lectin which is capable of showing broad interaction via oligomannosyl antigens is known as lectin GNA (Galanthus nivalis agglutinin). The N-oligomannosyl cores are embedded in N-glycans which are commonly expressed on the surface of numerous viral pathogens [13]. Once the lectin binds to the glycan, the virus structure may undergo conformational changes that result in the fusion of the virus and host to facilitate virus entry. S-proteins are specifically responsible for host cell entry by coronaviruses [14]. Figure 1 depicts a simplified entry mechanism of the viruses into host cells.