1. Introduction
In late December 2019, a viral outbreak of unknown etiology in Wuhan,
China was reported in which several patients were admitted to hospitals
with a diagnoses of pneumonia and respiratory distress (Bogoch et al.,
2020). This “viral pneumonia” was found to be linked to the Huanan
Seafood Market in Wuhan, China (Huang et al., 2020). This emerging novel
coronavirus (nCoV), was named SARS-CoV-2, and on February 11, 2020 the
WHO named the disease associated with SARS-CoV-2 Corona virus disease 19
(COVID-19) (Q. Li et al., 2020; Rothan & Byrareddy, 2020). Similar to
previously detected HCoVs, such as SARS-CoV and MERS-CoV, this virus is
known to infect people and spread rapidly from person-to-person through
droplets (Lewis, 2020). The COVID-19 outbreak was recognized as a
pandemic on March 11, 2020 (Cucinotta & Vanelli, 2020). As of May 29,
2020, the virus has surpassed 5,888,498 infections and 363,210 deaths
worldwide. At the same time, in the United States of America there are
1,743,235 confirmed cases and 102,516 deaths.
(https://coronavirus.jhu.edu/us-map)
CoVs are enveloped and positive-stranded RNA viruses that have large
viral genomes ranging from 26- 32 kb in length (Denison, Graham,
Donaldson, Eckerle, & Baric, 2011). Common HCoVs such as 229E and NL63
belong to alpha coronavirus genus, while comparatively OC43 and HKU1
belong to the genus betacoronavirus, which can cause mild and
self-limiting respiratory tract infections (Corman, Muth, Niemeyer, &
Drosten, 2018). In the last two decades, the pandemics associated with
SARS-CoV and MERS-CoV, betacoronaviruses, cause Severe Acute Respiratory
Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) respectively
(11,12). The antigenicity of the virus depends on the enveloped spike
protein, which is the major determinant of attachment and entry of the
virus into host cells (Sui et al., 2004). The viruses belonging to the
family Coronaviridae have a wide variety of hosts including: birds,
pigs, cats, dogs, bats, pangolins, and humans (Woo et al., 2012). These
beta coronaviruses have resulted in symptoms of varying severity ranging
from comparative symptoms of common cold affecting the upper respiratory
tract (URT), to more severe symptoms of bronchitis, pneumonia, and
associated fatalities affecting the lower respiratory tract (LRT)
(Peiris et al., 2003; Raj, Osterhaus, Fouchier, & Haagmans, 2014). The
outbreak of SARS pandemic in 2002 resulted in a 9.6 % fatality rate
from 8096 cases and almost 774 fatalities worldwide. (”World Health
Organization . Geneva (Switzerland): World Health Organization; 2003.
Summary of probable SARS cases with onset of illness from 1 November
2002 to 31 July 2003 ”). MERS which emerged in 2012 and observed for new
cases until October 2018, had 2229 confirmed cases and 791 deaths for a
higher rate of fatality near 35.5% (”World Health Organization . Geneva
(Switzerland): World Health Organization; 2019. MERS situation update,
December 2019,”). These viruses are known for being cross-species
(zoonotic) and human-to-human communicable from where transmission can
be coupled with severe pathological effects (Corman et al., 2018).
SARS-CoV and MERS-CoV use Angiotensin-Converting Enzyme 2 (ACE2) (W. Li
et al., 2003) and Dipeptidyl peptidase 4 (DPP-4) (Raj et al., 2013) as
receptors to enter host cells, respectively.
SARS-CoV-2 belongs to the same clade of beta coronaviruses as SARS-CoV
and MERS-CoV, with more than 80% and 50% sequence similarity,
respectively (Cui, Li, & Shi, 2019). The genome of SARS-CoV-2, which
was isolated from a cluster of patients with pneumonia in Wuhan, had
more than 90% nucleotide identity with the bat CoV, RaTG13 (Zhou et
al., 2020). The exact route of animal-to-human transmission of
SARS-CoV-2 is still unclear but genomic data suggest their evolution is
from bats to humans (Zhou et al., 2020) (Figure 1 ). Recent
study suggested that 99% sequence similarity of SARS-CoV-2 structural
proteins with coronavirus isolated from pangolins suggesting pangolins
as intermediate hosts (Xiao et al., 2020) (Figure 1 ). Another
study suggested that snakes could be an intermediate host for SARS-CoV-2
based on codon usage (Ji, Wang, Zhao, Zai, & Li, 2020) (Figure
1 ). In contrast, the bamboo rat has also been proposed to be the
intermediate host (Nanshan, 2020) (Figure 1 ). Despite active
investigation, the definitive animal reservoir responsible for
cross-species transmission of SARS-CoV-2 from animals to humans remains
elusive (Bassetti, Vena, & Giacobbe, 2020). Like SARS and MERS,
clinical symptoms of COVID-19 range from acute to severe. Characteristic
mild symptoms include fever, sore throat with a dry cough, respiratory
stress, and myalgia (Huang et al., 2020). In severe conditions,
bilateral lung ground-glass opacity is observed under chest-computed
tomography. (Acharya, Kevadiya, Gendelman, & Byrareddy, 2020; H. Shi et
al., 2020). Neurological manifestations like dizziness, headache,
ataxia, seizure with taste, smell and visual impairment were reported
(Mao et al., 2020) Histopathological reports showed diffuse alveolar
damage and pulmonary edema, indicating acute respiratory distress
syndrome (Rothan & Byrareddy, 2020; Xu et al., 2020), which was also
seen in SARS-CoV infection (Nicholls et al., 2003).
SARS-CoV-2 uses ACE2 as a receptor for binding and entering host cells,
which is facilitated by the host protease Transmembrane Serine Protease
2 (TMPRSS2) (Hoffmann et al., 2020). ACE2 is expressed in airway
epithelial cells, lung parenchyma, and vascular endothelial cells in the
kidney and small intestine (Hamming et al., 2004). Therapeutic
interventions for COVID-19 such as vaccines, antivirals, antibodies, etc
are an active area of investigation (Mukherjee, 2020) and several are
already in clinical trials (Scavone et al., 2020). In-vitro cell models
and organoids are also helpful to understand the virus entry, life cycle
and testing the efficacy of therapeutics (Takayama, 2020) but they are
unable to exhibit the exact pathological changes and lesions that are
specific to particular organs. Therefore, suitable biological relevant
animal models are necessary for testing the safety and efficacy of the
vaccines, antivirals and other potential therapeutics that are currently
in the pipeline.