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).