SARS -CoV-2 structure and virulence
The SARS-CoV-2 genome structure is about 29.9 kb in length and encodes four major structural proteins as well as several non-structural accessory proteins (Figure 1 ). The major proteins encoded are surface spike glycoprotein (S), the envelope glycoprotein protein (E), membrane glycoprotein (M), and nucleocapsid protein (N) (Figure 1 ) (Chan et al., 2020; Huang, Yang, Xu, Xu & Liu, 2020). Similar to SARS-CoV, the recent CoV-2 virus also enters the host cell by using the 150 kDa ‘S’ spike protein. One of the major mechanisms of virus entry known to date is that the virus uses the ‘S’ protein and the ACE-2 host receptor to facilitate its access into the host cell, where S is primed by the host cell serine protease, TMPRSS2 (Hoffmann et al., 2020; Walls, Park, Tortorici, Wall, McGuire & Veesler, 2020). Although ACE-2 is widely expressed in many organs and tissues, the respiratory tract remains the major port of entry. ACE-2 expression is known to be less in children in comparison to adults, and expression increases with smoking and chronic obstructive pulmonary disease (COPD) (Saheb Sharif-Askari et al., 2020; Sungnak, Huang, Becavin, Berg & Network, 2020). Infection is also reported in other tissues, including heart, liver, skin, kidney, intestinal tract, and adipose tissue (Al-Benna, 2020; Edler et al., 2020).
On the other hand, the heavily phosphorylated SARS-CoV-2 ‘N’ glycoprotein is associated with the viral genome and localizes to the ER-Golgi region, where it regulates viral replication (Fehr & Perlman, 2015). At the same time, other post-translational modifications are also identified (Fung & Liu, 2018). While the coronavirus ‘M’ protein is involved in determining the structure and shape of the virus, including stabilizing the N protein-RNA complex (Escors, Ortego, Laude & Enjuanes, 2001), the E structural protein helps in the production and maturation of the virus (Schoeman & Fielding, 2019). Their individual roles are reviewed in more detail elsewhere (Fung & Liu, 2018). Although these viruses also cause respiratory symptoms, the severity and the region of their manifestations are different. For example, MERS-CoV presents more gastrointestinal manifestation and kidney failure while SARS-CoV mainly manifests in the lower respiratory tract (LRT), possibly due to the difference in the host surface receptor affinity and distribution (Paules, Marston & Fauci, 2020). SARS-CoV entry is through the ACE-2 receptor, which is predominantly found in cells of the lower respiratory tract. On the other hand, MERS-CoV facilitates access through surface enzyme dipeptidyl peptidase 4 (DPP4), also known as CD26, which is widely expressed in the LRT, kidney, and gastrointestinal tract (GIT) (Park et al., 2019; Song, Gui, Wang & Xiang, 2018; Wan, Shang, Graham, Baric & Li, 2020). In comparison to these two viruses, the recent SARS-CoV-2 is highly infectious and aggressive, as evident from its exponential spread. SARS-CoV-2 is shown to have a higher affinity for the ACE-2 receptor than SARS-CoV (Song, Gui, Wang & Xiang, 2018). A wide distribution of this receptor across species depicts its transmission from animals to humans (Li, Qiao & Zhang, 2020).