Virology:
The virus was identified by Wu et al.(11) and named it WH-Human 1 , and
by Zhou et al., simultaneously, who named it 2019-nCoV (12). Later on,
the virus name was changed to “SARS-CoV-2” by the Coronavirus Study
Group (CSG) of International Committee on Taxonomy of Viruses (ICTV),
since it was found to be the sister virus of severe acute respiratory
syndrome coronavirus (SARS-CoV)(13). Based on this, the WHO officially
announced the virus name as SARS-CoV-2 and the infection as Covid-19 by
February 11, 2020 (14).
Coronaviruses belong to the
family Coronaviridae (subfamily Coronavirinae ) and are
capable of infecting various wild animals as well as humans where they
can cause diseases ranging from mild flu to severe respiratory
infections and sometimes fatal complications (13). Among the 6 CoVs
which are pathogenic to humans, 4 of them have led to mild respiratory
infections, however, the other 2 viruses; SARS and the Middle East
respiratory syndrome (MERS) were responsible for epidemics of severe
respiratory infections in 2003 and 2012 respectively(15). SARS and MERS
have a lower infectivity rate but a higher lethality than SARS-CoV-2
which showed tremendously higher infectivity with apparently lower
lethality rate(16).
SARS-CoV-2 is the 7th identified Corona virus and the 3rd zoonotic virus
of CoVs that has been transmitted from animals to humans after SARS and
MERS (17),(18). In fact, the Chinese horseshoe bats have been proposed
to serve as the primary source for SARS-CoV-2. It was reported that
SARS-CoV-2 genome has shown around 80% similarity with SARS (19) and
nearly all its encoded proteins are homologous with those of SARS(8).
Corona viruses are enveloped single stranded positive sense RNA viruses;
their RNA is approximately 30 Kbp. They have a spheroidal shape, their
diameter is 80–120 nm and their envelope holds the structural proteins;
spike (S), membrane (M), and envelope (E), and they include the
nucleocapsid (N) inside the virion which covers the RNA(20).
S is a glycoprotein that projects from the viral membrane, giving it the
crown shape and hence the corona virus name, it also helps in the
attachment of the virus to different surfaces leading to its high
stability and infectivity. Glycoprotein S is composed of 2 subunits: S1
which contains the receptor binding domain (RBD) and also has epitopes
that could be recognized by T and B lymphocytes and induce the
production of neutralizing antibodies; and S2 which induces the fusion
of the virion with the host cell membrane (16).
The surface angiotensin-converting enzyme 2 (ACE2), which is expressed
on type-I and -II alveolar cells of the lungs is the main receptor that
allows the entrance of SARS-CoV-2 into human host cells. Noteworthy, the
expression of ACE2 receptors is not only restricted to the lung cells
but their expression on small intestine enterocytes, kidney proximal
tubules cells, endothelial cells of arteries and veins, and the arterial
smooth muscle was also demonstrated which may explain the extrapulmonary
spread of SARS-CoV-2(21). Furthermore, homology modeling showed great
degree of structural resemblance between the receptor-binding domains of
SARS and SARS-CoV-2(22). However, the degree of affinity of the 2
viruses to their receptors may vary which may be the cause of the higher
infectivity and virulence of SARS-CoV-2 in comparison to SARS (23).
Binding between RBD of the virus and its receptor initiates
conformational changes of S protein which causes cleavage of S1 and S2
which is a fundamental step that enables S2 to induce the fusion of the
virus envelope with the cell membrane followed by the internalization of
the viral RNA into the cytoplasm of the host cells by endocytosis(20),
(24). Next, the viral RNA acts as a template for the translation of the
polyproteins pp1a and pp1b which are then cleaved into 5– 16
non-structural proteins (nsp2-nsp9), which in turn induce reorganization
of the membranes to form the vesicles where viral replication and
transcription complexes are formed then the assembly of the virions
starts and the mature virions are released from the cells by the
secretory pathway to infect the neighboring cells (20).
In addition, it was found that entry of the virus in helped by the
cellular host type 2 transmembrane serine protease (TMPRSS2) which is
expressed on many cell types and has a role in priming the S protein
leading to its cleavage at the S1/S2 site to enable fusion of the viral
envelope with the host cell membrane. Thus, TMPRSS2 could be a possible
biological target in therapies and vaccines strategies and the entry of
SARS-CoV-2 into the host cells could be prevented by TMPRSS2 inhibitor
(camostat mesylate). In fact, TMPRS2 inhibitor (camostat mesylate) is
already in use in Japan for treatment of pancreatitis which proposes its
possible benefit in treating Covid-19 cases(23).