All clinicians should keep themselves updated about

recent developments including global spread of the

diseases.
• Non-essential international travel should be avoided at
this time.
• People should stop spreading myths and false
information about the disease and try to allay panic and
anxiety of the public.

Conclusions

This new virus outbreak has challenged the economic,

medical and public health infrastructure of China and to
some extent, of other countries especially, its neighbours.
Time alone will tell how the virus will impact our lives here
in India. More so, future outbreaks of viruses and
pathogens of zoonotic origin are likely to continue.
Therefore, apart from curbing this outbreak efforts should
be made to
considerable protection in mice against a MERS- CoV
lethal challenge. Such antibodies may play a crucial role in
enhancing protective humoral responses against the
emerging CoVs by aiming appropriate epitopes and
functions of the S protein. The cross-neutralization ability
of SARS-CoV RBD- specific neutralizing MAbs
considerably relies on the resemblance between their
RBDs; therefore, SARS-CoV RBD-specific antibodies
could cross- neutralized SL CoVs, i.e., bat-SL-CoV strain
WIVI (RBD with eight amino acid differences from SARS-
CoV) but not bat-SL-CoV strain SHC014 (24 amino acid
differences).

Appropriate RBD-specific MAbs can be recognized by a

relative analysis of RBD of SARS- CoV-2 to that of SARS-
CoV, and cross-neutralizing SARS-CoV RBD-specific
MAbs could be explored for their effectiveness against
COVID-19 and further need to be assessed clinically. The
U.S. biotechnology company Regeneron is attempting to
recognize potent and specific MAbs to combat COVID-19.
An ideal therapeutic option suggested for SARS-CoV-2
(COVID-19) is the combination therapy comprised of
MAbs and the drug remdesivir (COVID-19). The SARS-
CoV-specific human MAb CR3022 is found to bind with
SARS-CoV-2 RBD, indicating its potential as a therapeutic
agent
proteins without the presence of S protein would not
confer any noticeable protection, with the absence of
detectable serum SARS-CoV-neutralizing antibodies .
Antigenic determinant sites present over S and N
structural proteins of SARS-CoV-2 can be explored as
suitable vaccine candidates. In the Asian population, S, E,
M, and N proteins of SARS- CoV-2 are being targeted for
developing subunit vaccines against COVID-19.
The identification of the immunodominant region among
the subunits and domains of S protein is critical for
developing an effective vaccine against the coronavirus.
The C-terminal domain of the SI subunit is considered the
immunodominant region of the porcine delta coronavirus S
protein. Similarly, further investigations are needed to
determine the immunodominant regions of SARS- CoV-2
for facilitating vaccine development.

However, our previous attempts to develop a universal

vaccine that is effective for both SARS- CoV and MERS-
CoV based on T-cell epitope similarity pointed out the
possibility of cross- reactivity among coronaviruses. That
can be made possible by selected potential vaccine
targets that are common to both viruses. SARS-CoV-2 has
been reported to be closely related to SARS-CoV. Hence,
knowledge and understanding of other clinical trials in
different phases are still ongoing elsewhere.

Immunomodulatory agents. SARS-CoV-2 triggers a strong

immune response which may cause cytokine storm
syndrome. Thus, immunomodulatory agents that inhibit
the excessive inflammatory response may be a potential
adjunctive therapy for COVID-19. Dexamethasone is a
corticosteroid often used in a wide range of conditions to
relieve inflammation through its anti-inflammatory and
immunosuppressant effects. Recently, the RECOVERY
trial found dexamethasone reduced mortality by about one
third in hospitalized patients with COVID-19 who received
invasive mechanical ventilation and by one fifth in patients
receiving oxygen. By contrast, no benefit was found in
patients without respiratory support".

Tocilizumab and sarilumab, two types of interleukin-6 (IL-

6) receptor-specific antibodies previously used to treat
various types of arthritis, including rheumatoid arthritis,
and cytokine release syndrome, showed effectiveness in
the treatment of severe COVID-19 by attenuating the
cytokine storm in a small uncontrolled trial. Bevacizumab
is an anti-vascular endothelial growth factor (VEGF)
medication that could potentially reduce pulmonary
oedema in patients with severe COVID-19. Eculizumab is
a specific monoclonal antibody that inhibits the
proinflammatory complement protein C5. Preliminary
results showed that it induced a drop of inflammatory
markers and C-reactive protein levels, suggesting its
potential to be an option for the treatment of severe
COVID-19 (REF).

another study, the average reproductive number of

COVID-19 was found to be 3.28, which is significantly
higher than the initial WHO estimate of 1.4 to 2.5 . It is too
early to obtain the exact Ro value, since there is a
possibility of bias due to insufficient data. The higher Ro,
value is indicative of the more significant potential of
SARS-CoV-2 transmission in a susceptible population.
This is not the first time where the culinary practices of
China have been blamed for the origin of novel
coronavirus infection in humans. Previously, the animals
present in the live-animal market were identified to be the
intermediate hosts of the SARS outbreak in China .
Several wildlife species were found to harbor potentially
evolving coronavirus strains that can overcome the
species barrier. One of the main principles of Chinese
food culture is that live- slaughtered animals are
considered more nutritious.

After 4 months of struggle that lasted from December

2019 to March 2020, the COVID-19 situation now seems
under control in China. The wet animal markets have
reopened, and people have started buying bats, dogs,
cats, birds, scorpions, badgers, rabbits, pangolins (scaly
anteaters), minks, soup from palm civet, ostriches,
hamsters, snapping turtles, ducks, fish, Siamese
crocodiles, and other
been used based on the experience with SARS and
MERS. In a historical control study in patients with SARS,
patients treated with lopinavir- ritonavir with ribavirin had
better outcomes as compared to those given ribavirin
alone.
In the case series of 99 hospitalized patients with COVID-
19 infection from Wuhan, oxygen was given to 76%, non-
invasive ventilation in 13%, mechanical ventilation in 4%,
extracorporeal membrane oxygenation (ECMO) in 3%,
continuous renal replacement therapy (CRRT) in 9%,
antibiotics in 71%, antifungals in 15%, glucocorticoids in
19% and intravenous immunoglobulin therapy in 27%.
Antiviral therapy consisting of oseltamivir, ganciclovir and
lopinavir- ritonavir was given to 75% of the patients. The
duration of non-invasive ventilation was 4-22 d [median 9
d] had >95% homology with the bat coronavirus and >
70% similarity with the SARS-CoV. Environmental
samples from the Wuhan sea food market also tested
positive, signifying that the virus originated from there. The
number of cases started increasing exponentially, some of
which did not have exposure to the live animal market,
suggestive of the fact that human-to-human transmission
was occurring. The first fatal case was reported on 11th
Jan 2020. The massive migration of Chinese during the
Chinese New Year fueled the epidemic. Cases in other
provinces of China, other countries (Thailand, Japan and
South Korea in quick succession) were reported in people
who were returning from Wuhan. Transmission to
healthcare workers caring for patients was described on
20th Jan, 2020. By 23rd January, the 11 million population
of Wuhan was placed under lock down extended to other
cities of Hupe province. Cases of COVID-19 in countries
outside China were reported in those with no history of
travel to China suggesting that local human-to- human
transmission was occurring in these countries. Airports in
different countries including India put in screening
mechanisms to detect symptomatic people returning from
China and placed them in isolation and testing them for
COVID-19. Soon it was apparent that the infection could
be transmitted from asymptomatic people and also before
onset of symptoms. Therefore, countries including India
who evacuated their citizens from Wuhan through special
flights or had travelers returning from China, placed all
people symptomatic or otherwise in isolation for 14 d and
tested them for the virus.

Cases continued to increase exponentially and modelling

studies; fever, cough, and sputum. Hence, the client must
be on the look-out for the possible occurrence of atypical
clinical manifestations to avoid the possibility of missed
diagnosis. The early transmission ability of SARS-CoV-2
was found to be similar to or slightly higher than that of
SARS-CoV. reflecting that it could be controlled despite
moderate to high transmissibility .

Increasing reports of SARS-CoV-2 in sewage and

wastewater warrants the need for further investigation due
to the possibility of fecal-oral transmission. SARS-CoV-2
present in environmental compartments such as soil and
water will finally end up in the wastewater and sewage
sludge of treatment plants. Therefore, we have to
reevaluate the current wastewater and sewage sludge
treatment procedures and introduce advanced techniques
that are specific and effective against SARS-CoV-2. Since
there is active shedding of SARS-CoV-2 in the stool, the
prevalence of infections in a large population can be
studied using wastewater-based epidemiology. Recently,
reverse transcription- quantitative PCR (RT-qPCR) was
used to enumerate the copies of SARS-CoV-2 RNA
concentrated from wastewater collected from a
wastewater treatment plant. The calculated viral RNA copy
numbers determine the number of infected individuals.

CONVALESCENT PLASMA THERAPY

Guo Yanhong, an official with the National Health

Commission (NHC), stated that convalescent plasma
therapy is a significant method for treating severe COVID-
19 patients. Among the COVID-19 patients currently
receiving convalescent plasma therapy in the virus-hit
Wuhan, one has been discharged from hospital, as
reported by Chinese science authorities on Monday, 17th
February 2020 in Beijing. The first dose of convalescent
plasma from a COVID-19 patient was collected on 1st and
9th February 2020 from a severely ill patient who was
given treatment at a hospital in Jiangxia District in Wuhan.
The presence of the virus in patients is minimised by the
antibodies in the convalescent plasma. Guiqiang stated
that donating plasma may cause minimal harm to the
donor and that there is nothing to be worried about.
Plasma donors must be cured patients and discharged
from hospital. Only plasma is used, whereas red blood
cells (RBC), white blood cells (WBC) and blood platelets
are transfused back into the donor's body. Wang alleged
that donor's plasma will totally improve to its initial state
after one or 2 weeks from the day of plasma donation of
around 200 to 300 milliliters.

Epidemiology and Pathogenesis

All ages are susceptible. Infection is transmitted through

large droplets generated during coughing and sneezing by
symptomatic patients but can also occur from
asymptomatic people and before onset of symptoms.
Studies have shown higher viral loads in the nasal cavity
as compared to the throat with no difference in viral
burden between symptomatic and asymptomatic people.
Patients can be infectious for as long as the symptoms
last and even on clinical recovery. Some people may act
as super spreaders; a UK citizen who attended a
conference in Singapore infected 11 other people while
staying in a resort in the French Alps and upon return to
the UK. These infected droplets can spread 1-2 m and
deposit

Prevention

Since at this time there are no approved treatments for

this infection, prevention is crucial. Several properties of
this virus make prevention difficult namely, non- specific
features of the disease, the infectivity even before onset of
symptoms in the incubation period, transmission from
asymptomatic people, long incubation period, tropism for
mucosal surfaces such as the conjunctiva, prolonged
duration of the illness and transmission even after clinical
recovery.

Isolation of confirmed or suspected cases with mild illness

at home is recommended. The ventilation at home should
be good with sunlight to allow for destruction of virus.
Patients should be asked to wear a simple surgical mask
and practice cough hygiene.

absence of this protein is related to the altered virulence of

coronaviruses due to changes in morphology and tropism.
The E protein consists of three domains, namely, a short
hydrophilic amino terminal, a large hydrophobic
transmembrane domain, and an efficient C-terminal
domain. The SARS-CoV-2 E protein reveals a similar
amino acid constitution without any substitution.

N Protein

The N protein of coronavirus is multipurpose. Among

several functions, it plays a role in complex formation with
the viral genome, facilitates M protein interaction needed
during virion assembly, and enhances the transcription
efficiency of the virus. It contains three highly conserved
and distinct domains, namely, an NTD, an RNA-binding
domain or a linker region (LKR), and a CTD. The NTD
binds with the 3' end of the viral genome, perhaps via
electrostatic interactions, and is highly diverged both in
length and sequence. The charged LKR is serine and
arginine rich and is also known as the SR (serine and
arginine) domain. The LKR is capable of direct interaction
with in vitro RNA interaction and is responsible for cell
signaling. It also modulates the antiviral response of the
host by working as an antagonist for interferon prongs,
face mask, high flow nasal cannula (HFNC) or non-
invasive ventilation is indicated. Mechanical ventilation
and even extra corporeal membrane oxygen support may
be needed. Renal replacement therapy may be needed in
some. Antibiotics and antifungals are required if co-
infections are suspected or proven. The role of
corticosteroids is unproven; while current international
consensus and WHO advocate against their use, Chinese
guidelines do recommend short term therapy with low-to-
moderate dose corticosteroids in COVID-19 ARDS.
Detailed guidelines for critical care management for
COVID-19 have been published by the WHO. There is, as
of now, no approved treatment for COVID-19. Antiviral
drugs such as ribavirin, lopinavir-ritonavir have been used
based on the experience with SARS and MERS. In a
historical way, knowledge and understanding of S protein-
based vaccine development in SARS-CoV will help to
identify potential S protein vaccine candidates in SARS-
CoV-2. Therefore, vaccine strategies based on the whole
S protein, S protein subunits, or specific potential epitopes
of S protein appear to be the most promising vaccine
candidates against coronaviruses. The RBD of the S1
subunit of S protein has a superior capacity to induce
neutralizing antibodies. This property of the RBD can be
utilized for designing potential SARS-CoV vaccines either
by using RBD-containing recombinant proteins or
recombinant vectors that encode RBD. Hence, the
superior genetic similarity existing between SARS-CoV-2
and SARS- CoV can be utilized to repurpose vaccines that
have proven in vitro efficacy against SARS-CoV to be
utilized for SARS-CoV-2. The possibility of cross-
protection in COVID-19 was evaluated by comparing the S
protein sequences of SARS-CoV-2 with that of SARS-
CoV. The comparative analysis confirmed that the variable
residues were found concentrated on the S1 subunit of S
protein, an important vaccine target of the virus. Hence,
the possibility of SARS-CoV-specific neutralizing
antibodies providing cross-protection to COVID-19 might
be lower. Further genetic analysis is required including
IL2, IL7, IL10, GCSF, IP10, MCP1, MIP1A, and TNFa. The
median time from onset of symptoms to dyspnea was 5 d,
hospitalization 7 d and acute respiratory distress
syndrome (ARDS) 8 d. The need for intensive care
admission was in 25- 30% of affected patients in published
series. Complications witnessed included acute lung
injury, ARDS, shock and acute kidney injury. Recovery
started in the 2nd or 3rd wk. The median duration of
hospital stay in those who recovered was 10 d. Adverse
outcomes and death are more common in the elderly and
those with underlying co-morbidities (50-75% of fatal
cases). Fatality rate in hospitalized adult patients ranged
from 4 to 11%. The overall case fatality rate is estimated
to range between 2 and 3%.

Interestingly, disease in patients outside Hubei province

has been system.

Bovine coronaviruses (BoCoVs) are known to infect

several domestic and wild ruminants. BoCoV inflicts
neonatal calf diarrhea in adult cattle, leading to bloody
diarrhea (winter dysentery) and respiratory disease
complex (shipping fever) in cattle of all age groups.
BoCoV-like viruses have been noted in humans,
suggesting its zoonotic potential as well. Feline enteric
and feline infectious peritonitis (FIP) viruses are the two
major feline CoVs, where feline CoVs can affect the
gastrointestinal tract, abdominal cavity (peritonitis).
respiratory tract, and central nervous system. Canines are
also affected by CoVs that fall under different genera,
namely, canine enteric coronavirus in Alphacoronavirus
and canine respiratory coronavirus in Betacoronavirus,
affecting the enteric and respiratory tract, respectively.
IBV. under Gammacoronavirus, causes diseases of
respiratory, urinary, and reproductive systems, with
substantial economic losses in chickens. In small
laboratory animals, mouse hepatitis virus, rat
sialodacryoadenitis coronavirus, and guinea pig and rabbit
coronaviruses are the major CoVs associated with disease
manifestations like enteritis. hepatitis, and respiratory
infections.

Swine acute diarrhea syndrome coronavirus this emerging

virus will establish a niche in humans and coexist with us
for a long time. Before clinically approved vaccines are
widely available, there is no better way to protect us from
SARS-CoV-2 than personal preventive behaviors such as
social distancing and wearing masks, and public health
measures, including active testing, case tracing and
restrictions on social gatherings. Despite a flood of SARS-
CoV-2 research published every week, current knowledge
of this novel coronavirus is just the tip of the iceberg. The
animal origin and cross-species infection route of SARS-
CoV-2 are yet to be uncovered. The molecular
mechanisms of SARS-CoV-2 infection pathogenesis and
virus-host. The virus can remain viable on surfaces for
days in favourable atmospheric conditions but are
destroyed in less than a minute by common disinfectants
like sodium hypochlorite, hydrogen peroxide etc.
Infection is acquired either by inhalation of these droplets
or touching surfaces contaminated by them and then
touching the nose, mouth and eyes. The virus is also
present in the stool and contamination of the water supply
and subsequent transmission via aerosolization/feco oral
route is also hypothesized. As per current information,
transplacental transmission from pregnant women to their
fetus has not been described [14]. However, neonatal
disease due to post natal transmission is described. The
incubation period varies from 2 to 14 d [median 5 d].
Studies have identified angiotensin receptor.

Interestingly, disease in patients outside Hubei province

has been reported to be milder than those from Wuhan.
Similarly, the severity and case fatality rate in patients
outside China has been reported to be milder. This may
either be due to selection bias wherein the cases reporting
from Wuhan included only the severe cases or due to
predisposition of the Asian population to the virus due to
higher expression of ACE2 receptors on the respiratory
mucosa.

Disease in neonates, infants and children has been also

reported to be significantly milder than their adult
counterparts. In a series of 34 children admitted to a
hospital in Shenzhen, China between January 19th and
February 7th, there were 14 males and 20 females. The
median age was 8 y 11 mo and in 28 children the infection
was linked to a family member. Cases continued to
increase exponentially and modelling studies reported an
epidemic doubling time of 1.8 d. In fact on the 12th of
February, China changed its definition of confirmed cases
to include patients with negative/pending molecular tests
but with clinical, radiologic and epidemiologic features of
COVID-19 leading to an increase in cases by 15,000 in a
single day. As of 05/03/2020 96,000 cases worldwide
(80,000 in China) and 87 other countries and 1
international conveyance (696, in the cruise ship Diamond
Princess parked off the coast of Japan) have been
reported. It is important to note that while the number of
new cases has reduced in China lately, they have
increased exponentially in other countries including South
Korea, Italy and Iran. Of those infected, 20% are in critical
only a matter of time before another zoonotic coronavirus
results in an epidemic by jumping the so-called species
barrier.

The host spectrum of coronavirus increased when a novel

coronavirus, namely, SW1, was recognized in the liver
tissue of a captive beluga whale (Delphinapterus leucas).
In recent decades, several novel coronaviruses were
identified from different animal species. Bats can harbor
these viruses without manifesting any clinical disease but
are persistently infected. They are the only mammals with
the capacity for self-powered flight, which enables them to
migrate long distances, unlike land mammals. Bats are
distributed worldwide and also account for about a fifth of
all mammalian species. This makes them the ideal
reservoir host for many viral agents and also the source of
novel coronaviruses that have yet to be identified. It has
become a necessity to study the diversity of coronavirus in
the bat population to prevent future outbreaks that could
jeopardize livestock and public health. The repeated
outbreaks caused by bat-origin coronaviruses calls for the
development of efficient molecular surveillance strategies
for studying Betacoronavirus among animals, especially in
the Rhinolophus bat family. Chinese bats have high
commercial value.
However, in another case study, the authors raised
concerns over the efficacy of hydroxychloroquine-
azithromycin in the treatment of COVID-19 patients. since
no observable effect was seen when they were used. In
some cases, the treatment was discontinued due to the
prolongation of the QT interval. Hence, further randomized
clinical trials are required before concluding this matter.

Recently, another FDA-approved drug. ivermectin, was

reported to inhibit the in vitro replication of SARS-CoV-2.
The findings from this study indicate that a single
treatment of this drug was able to induce an -5,000-fold
reduction in the viral RNA at 48 h in cell culture. One of
the main disadvantages that limit the clinical utility of
ivermectin is its potential to cause cytotoxicity. However,
altering the vehicles used in the formulations, the
pharmacokinetic properties can be modified, thereby
having significant control over the systemic concentration
of ivermectin (338). Based on the pharmacokinetic
simulation, it was also found that ivermectin may have
limited therapeutic utility in managing COVID-19, since the
inhibitory concentration that has to be achieved for
effective anti-SARS-CoV-2 activity is far higher.
SARS or MERS-CoV outbreak. However, there has been
concern regarding the impact of SARS-CoV-2/COVID-19
on pregnancy. Researchers have mentioned the
probability of in utero transmission of novel SARS-CoV-2
from COVID- 19-infected mothers to their neonates in
China based upon the rise in IgM and IgG antibody levels
and cytokine values in the blood obtained from newborn
infants immediately postbirth; however, RT-PCR failed to
confirm the presence of SARS-CoV-2 genetic material in
the infants. Recent studies show that at least in some
cases, preterm delivery and its consequences are
associated with the virus. Nonetheless, some cases have
raised doubts for the likelihood of vertical transmission.

COVID-19 infection was associated with pneumonia, and

some developed acute respiratory distress syndrome
(ARDS). The blood biochemistry indexes, such as
albumin, lactate dehydrogenase, C- reactive protein,
lymphocytes (percent), and neutrophils (percent) give an
idea about the disease severity in COVID-19 infection.
During COVID-19, patients may present leukocytosis.
leukopenia with lymphopenia. hypoalbuminemia, and an
increase of lactate dehydrogenase, aspartate
transaminase, alanine aminotransferase, bilirubin, and,
especially, D-dimer was linked to a family member and 26
children had history of travel/residence to Hubei province
in China. All the patients were either asymptomatic (9%)
or had mild disease. No severe or critical cases were
seen. The most common symptoms were fever (50%) and
cough (38%). All patients recovered with symptomatic
therapy and there were no deaths. One case of severe
pneumonia and multiorgan dysfunction in a child has also
been reported. Similarly the neonatal cases that have
been reported have been mild.

Diagnosis

A suspect case is defined as one with fever, sore throat

and cough who has history of travel to China or other
areas of persistent local transmission or contact with
patients with similar travel history or those with confirmed
or even die, whereas most young people and children
have only mild diseases (non-pneumonia or mild
pneumonia) or are asymptomatic. Notably, the risk of
disease was not higher for pregnant women. However,
evidence of transplacental transmission of SARS-CoV-2
from an infected mother to a neonate was reported,
although it was an isolated case. On infection, the most
common symptoms are fever, fatigue and dry cough. Less
common symptoms include sputum production, headache,
haemoptysis, diarrhoea, anorexia, sore throat, chest pain,
chills and nausea and vomiting in studies of patients in
China. Self-reported olfac- tory and taste disorders were
also reported by patients in Italy. Most people showed
signs of diseases after an incubation period of 1-14 days
(most commonly around 5 days), and dyspnoea and
pneumonia developed within a median time of 8 days from
illness onset".
In a report of 72,314 cases in China, 81% of the cases
were classified as mild, 14% were severe cases that
required ventilation in an intensive care unit (ICU) and a
5% were critical (that is, the patients had respiratory
failure, septic shock and/or multiple organ dysfunction or
failure). On admission, ground-glass opacity was the most
common radiologic finding on chest computed tomography
(CT). Most patients also developed marked lymphopenia,
similar to what was observed in patients with SARS and
MERS, and non-survivors developed severer lymphopenia
over time. Compared with non-ICU patients, ICU patients
had higher levels of persistent local transmission or
contact with patients with similar travel history or those
with confirmed COVID-19 infection. However cases may
be asymptomatic or even without fever. A confirmed case
is a suspect case with a positive molecular test.

Specific diagnosis is by specific molecular tests on

respiratory samples (throat swab/ nasopharyngeal swab/
sputum/ endotracheal aspirates and bronchoalveolar
lavage). Virus may also be detected in the stool and in
severe cases, the blood. It must be remembered that the
multiplex PCR panels currently available do not include
the COVID-19. Commercial tests are also not available at
present. In a suspect case in India, the appropriate sample
has to be sent to designated reference labs in India or the
National Institute of Virology in Pune. As the epidemic
progresses, commercial tests in Yunnan. This novel bat
virus, denoted 'RmYN02, is 93.3% identical to SARS-CoV-
2 across the genome. In the long lab gene, it exhibits
97.2% identity to SARS-CoV-2, which is even higher than
for RaTG13 (REF). In addition to RaTG13 and RmYN02,
phylogenetic analysis shows that bat coronaviruses ZC45
and ZXC21 previously detected in Rhinolophus pusillus
bats from eastern China also fall into the SARS-CoV-2
lineage of the subgenus Sarbecovirus. The discovery of
diverse bat coronaviruses closely related to SARS-CoV-2
suggests that bats are possible reservoirs of SARS-CoV-2
(REF). Nevertheless, on the basis of current findings, the
divergence between SARS-CoV-2 and related bat
coronaviruses likely represents more than 20 years of
sequence evolution, suggesting that these bat
coronaviruses can be regarded only as the likely
evolutionary precursor of SARS-CoV-2 but not as the
direct progenitor of SARS-CoV-2 (REF).

Beyond bats, pangolins are another wildlife host probably

linked with SARS-CoV-2. Multiple SARS-CoV-2- related
viruses have been identified in tissues of Malayan
pangolins smuggled from Southeast Asia into southern
China from 2017 to 2019. These viruses from pangolins
independently seized by Guangxi and Guangdong
provincial customs belong to two distinct sub lineages.
The Guangdong strains, which were isolated or
sequenced by different research groups from smuggled
pangolins, have 99.8% sequence identity with each other.
They are very closely related to SARS-CoV-2, exhibiting
92.4% sequence similarity. Notably, the RBD of
Guangdong pangolin coronaviruses is highly similar to that
of SARS-CoV-2. The receptor-binding motif (RBM; which
is part of the RBD) of these viruses has only one amino
acid variation from SARS-CoV-2, and it is identical to that
of SARS-CoV-2 in all five critical
identified angiotensin receptor 2 (ACE₂ ) as the receptor
through which the virus enters the respiratory mucosa.

The basic case reproduction rate (BCR) is estimated to

range from 2 to 6.47 in various modelling studies. In
comparison, the BCR of SARS was 2 and 1.3 for
pandemic flu H1N1 2009.

Clinical Features

The clinical features of COVID-19 are varied, ranging from

asymptomatic state to acute respiratory distress syndrome
and multi organ dysfunction. The common clinical features
include fever (not in all), cough, sore throat, headache,
fatigue, headache, myalgia and breathlessness.
Conjunctivitis has also been described.
recovered patients and used for plasma transfusion twice
in a volume of 200 to 250 ml on the day of collection. At
present, treatment for sepsis and ARDS mainly involves
antimicrobial therapy, source control, and supportive care.
Hence, the use of therapeutic plasma exchange can be
considered an option in managing such severe conditions.
Further randomized trials can be designed to investigate
its efficacy.

Potential Therapeutic Agents

Potent therapeutics to combat SARS-CoV-2 infection

include virus binding molecules, molecules or inhibitors
targeting particular enzymes implicated in replication and
transcription process of the virus, helicase inhibitors, vital
viral proteases and proteins. protease inhibitors of host
cells, endocytosis inhibitors, short interfering RNA
(siRNA). neutralizing antibodies, MAbs against the host
receptor, MAbs interfering with the S1 RBD, antiviral
peptide aimed at S2, and natural drugs/medicines (7, 166,
186). The S protein acts as the critical target for
developing CoV antivirals, like inhibitors of S protein and S
cleavage, neutralizing antibodies, RBD-ACE2 blockers,
siRNAs, blockers of the fusion core, and proteases.

All of these therapeutic approaches have revealed

Origin and Spread of COVID-19
In December 2019, adults in Wuhan, capital city of Hubei
province and a major transportation hub of China started
presenting to local hospitals with severe pneumonia of
unknown cause. Many of the initial cases had a common
exposure to the Huanan wholesale seafood market that
also traded live animals. The surveillance system (put into
place after the SARS outbreak) was activated and
respiratory samples of patients were sent to reference labs
for etiologic investigations. On December 31st 2019,
China notified the outbreak to the World Health
Organization and on 1st January the Huanan sea food
market was closed. On 7th January the virus was
identified as a coronavirus that had >95% homology with
the bat infections clinically or through routine lab tests.
Therefore travel history becomes important. However, as
the epidemic spreads, the travel history will become
irrelevant.

Treatment

Treatment is essentially supportive and symptomatic.

The first step is to ensure adequate isolation (discussed

later) to prevent transmission to other contacts, patients
and healthcare workers. Mild illness should be managed
at home with counseling about danger signs. The usual
principles are maintaining hydration and nutrition and
controlling fever and cough. Routine use of antibiotics and
antivirals such as oseltamivir should be avoided in
confirmed cases. In hypoxic patients, provision of oxygen
through nasal prongs, face mask, high flow nasal with
COVID-19 showed typical features on initial CT, including
bilateral multilobar ground-glass opacities with a
peripheral or posterior distribution. Thus, it has been
suggested that CT scanning combined with repeated swab
tests should be used for individuals with high clinical
suspicion of COVID-19 but who test negative in initial
nucleic acid screening. Finally, SARS-CoV-2 serological
tests detecting antibodies to Nor S protein could
complement molecular diagnosis, particularly in late
phases after disease onset or for retro- spective studies
however, the extent and duration of immune responses
are still unclear, and available serological tests differ in
their sensitivity and specificity, all of which need to be
taken into account when one is deciding on serological
tests and interpreting their results or potentially in the
future test for T cell responses.

Therapeutics

To date, there are no generally proven effective therapies

for COVID-19 or antivirals against SARS-CoV-2, although
some treatments have shown some benefits in certain
subpopulations of patients or for certain end points (see
later). Researchers and manufacturers are conducting
large-scale clinical trials to evaluate various therapies for
COVID-19. As of 2 October 2020, there were about 405
therapeutic drugs in development for COVID-19, and
nearly 318 in human clinical trials (COVID-19 vaccine and
therapeutics tracker). In the following sections, we
summarize potential therapeutics against SARS-CoV-2 on
the basis of published clinical data and experience.
comorbidities), it may progress to pneumonia, acute
respiratory distress syndrome (ARDS) and multi organ
dysfunction. Many people are asymptomatic. The case
fatality rate is estimated to range from 2 to 3%. Diagnosis
is by demonstration of the

virus in respiratory secretions by special molecular tests.

Common laboratory findings include normal/ low white cell
counts with elevated C- reactive protein (CRP). The
computerized tomographic chest scan is usually abnormal
even in those with no symptoms or mild disease.

Treatment is essentially supportive; role of antiviral agents

is yet to be established. Prevention entails home isolation
of suspected cases and those with mild illnesses and strict
infection control measures at hospitals that include contact
and droplet precautions. The virus spreads faster than its
two ancestors the SARS-COV epidemic progresses,
commercial tests will become available.
Other laboratory investigations are usually non specific.
The white cell count is usually normal or low. There may
be lymphopenia; a lymphocyte count <1000 has been
associated with severe disease. The platelet count is
usually normal or mildly low. The CRP and ESR are
generally elevated but procalcitonin levels are usually
normal. A high procalcitonin level may indicate a bacterial
co-infection. The ALT/AST, prothrombin time, creatinine,
D-dimer, CPK and LDH may be elevated and high levels
are associated with severe disease.

The chest X-ray (CXR) usually shows bilateral infiltrates

but may be normal in early disease. The CT is more
sensitive and specific. CT imaging generally shows
infiltrates, ground glass opacities and sub segmental and
chest discomfort, and in severe cases dyspnea and
bilateral lung infiltration. Among the first 27 documented
hospitalized patients, most cases were epidemicologically
linked to Huanan Seafood Wholesale Market a wet market
located in downtown Wuhan, which sells not only seafood
but also live animals, including poultry and wildlife".
According to a retrospective study, the onset of the first
known case dates back to 8 December 2019 (REF). On 31
December, Wuhan Municipal Health Commission notified
the public of a pneumonia out- break of unidentified cause
and informed the World Health Organization (WHO).
By metagenomic RNA sequencing and virus isolation from
bronchoalveolar lavage fluid samples from patients with
severe pneumonia, independent teams of Chinese
scientists identified that the causative agent of this
emerging disease is a betacoronavirus that had never
been seen before. On 9 January 2020, the result of this
etiological identification was publicly announced. The first
genome sequence of the novel coronavirus was published
on the Virological website on 10 January, and more nearly
complete genome sequences determined by different
research institutes were them released via the GISAID
database on 12 January. Later, more patients with no
history of exposure to Huanan Seafood Wholesale Market
were identified. Several familial clusters of infection were
reported and nosocomial infection also occurred in health-
care facilities. All these cases provided clear evidence for
human-to-human transmission of the new virus-14 As the
outbreak coincided with the approach of the lunar New
Year, travel between cities before the festival facilitated
virus transmission in China. This novel coronavirus
pneumonia soon spread to other cities in Hube province
and to other parts of China. Within 1 month. such instance
was in 2002-2003 when a new coronavirus of the ẞ
genera and with origin in bats crossed over to humans via
the intermediary host of palm civet cats in the Guangdong
province of China. This virus, designated as severe acute
respiratory syndrome coronavirus affected 8422 people
mostly in China and Hong Kong and caused 916 deaths
(mortality rate 11%) before being contained. Almost a
decade later in 2012, the Middle East respiratory
syndrome coronavirus (MERS-CoV), also of bat origin,
emerged in Saudi Arabia with dromedary camels as the
intermediate host and affected 2494 people and caused
858 deaths (fatality rate 34%).

In the case series of children discussed earlier, all children

recovered with basic treatment and did not need intensive
care.

There is anecdotal experience with use of remdeswir, a

broad spectrum anti RNA drug developed for Ebola in
management of COVID-19. More evidence is needed
before these drugs are recommended. Other drugs
proposed for therapy are arbidol (an antiviral drug
available in Russia and China), intravenous
immunoglobulin, interferons, chloroquine and plasma of
patients recovered from COVID-19. Additionally,
recommendations about using traditional Chinese herbs
find place in the Chinese guidelines.

Prevention
exponentially in other countries including South Korea,
Italy and Iran. Of those infected, 20% are in critical
condition, 25% have recovered, and 3310 (3013 in China
and 297 in other countries) have died. India, which had
reported only 3 cases till 2/3/2020, has also seen a
sudden spurt in cases. By 5/3/2020, 29 cases had been
reported; mostly in Delhi, Jaipur and Agra in Italian tourists
and their contacts. One case was reported in an Indian
who traveled back from Vienna and exposed a large
number of school children in a birthday party at a city
hotel. Many of the contacts of these cases have been
quarantined.

These numbers are possibly an underestimate of the

infected and dead due to limitations of surveillance and
testing. Though the SARS-CoV-2 originated from bats, the
intermediary
lower respiratory tracts. Acute viral interstitial pneumonia
and humoral and cellular immune responses were
observed. Moreover, prolonged virus shedding peaked
early in the course of infection in asymptomatic macaques,
and old monkeys showed severer interstitial pneumonia
than young monkeys", which is similar to what is seen in
patients with COVID-19. In human ACE2-transgenic mice
infected with SARS-CoV-2, typical interstitial pneumonia
was present, and viral anti- gens were observed mainly in
the bronchial epithelial cells, macrophages and alveolar
epithelia. Some human ACE2-transgenic mice even died
after infection In wide-type mice, a SARS-CoV-2 mouse-
adapted strain with the N501Y alteration in the RBD of the
S protein was generated at passage 6. Interstitial
pneumonia and inflammatory responses were found in
both young and aged mice after infection with the mouse-
adapted strain. Golden hamsters also showed typical
symptoms after being infected with SARS-CoV-2 (REF). In
other animal models, including cats and ferrets, SARS-
CoV-2 could efficiently replicate in the upper respiratory
tract but did not induce severe clinical symptoms. As
trans- mission by direct contact and air was observed in
infected ferrets and hamsters, these animals could be
used to model different transmission modes of COVID-19
(REFS77-79). Animal models offer important information
for understanding the pathogenesis of SARS-CoV-2
infection and the transmission dynamics of SARS- CoV-2,
and are important to evaluate the efficacy of antiviral
therapeutics and vaccines.

Clinical and epidemiological features

It appears that all ages of the population are susceptible to

SARS-CoV-2 infection, and the median age of infection is
around 50 years. However, clinical manifestations differ
with age. In general, older men (>60 years old) with co-
morbidities are more likely to develop severe respiratory
disease that requires hospitalization
article gives a bird's eye view about this new virus. Since
knowledge about this virus is rapidly evolving, readers are
urged to update themselves regularly.

History

Coronaviruses are enveloped positive sense RNA viruses

ranging from 60 nm to 140 nm in diameter with spike like
projections on its surface giving it a crown like appearance
under the electron microscope; hence the name
coronavirus. Four corona viruses namely HKU1, NL63,
229E and OC43 have been in circulation in humans, and
generally cause mild respiratory disease.

There have been two events in the past two decades

wherein crossover of animal betacorona viruses to
humans has resulted in severe disease. The first such
instance was in 2002-2003.
(entertainment parks etc). China is also considering
introducing legislation to prohibit selling and trading of wild
animals.

The international response has been dramatic. Initially,

there were massive travel restrictions to China and people
returning from China/ evacuated from China are being
evaluated for clinical symptoms, isolated and tested for
COVID-19 for 2 weeks even if asymptomatic. However,
now with rapid world wide spread of the virus these travel
restrictions have extended to other countries. Whether
these efforts will lead to slowing of viral spread is not
known.

A candidate vaccine is under development.

Practice Points from an Indian Perspective

pandemic flu where patients were asked to resume

work/school once afebrile for 24 h or by day 7 of illness.
Negative molecular tests were not a prerequisite for
discharge.

At the community level, people should be asked to avoid

crowded areas and postpone non-essential travel to
places with ongoing transmission. They should be asked
to practice cough hygiene by coughing in sleeve/ tissue
rather than hands and practice hand hygiene frequently
every 15-20 min. Patients with respiratory symptoms
should be asked to use surgical masks. The use of mask
by healthy people in public places has not shown to
protect against respiratory viral infections and is currently
not recommended by WHO. However, in China, the public
has been asked to wear masks in public and especially in
crowded places and large scale gatherings are prohibited
(entertainment parks etc). China is also risk regions. It is
derived from a live attenuated strain of Mycobacterium
bovis. At present, three new clinical trials have been
registered to evaluate the protective role of BCG
vaccination against SARS- CoV-2. Recently, a cohort
study was conducted to evaluate the impact of childhood
BCG vaccination in COVID-19 PCR positivity rates.
However, childhood BCG vaccination was found to be
associated with a rate of COVID-19-positive test results
similar to that of the nonvaccinated group. Further studies
are required to analyze whether BCG vaccination in
childhood can induce protective effects against COVID-19
in adulthood. Population genetic studies conducted on 103
genomes identified that the SARS-CoV-2 virus has
evolved into two major types, L and S. Among the two
types, L type is expected to be the most prevalent (-70%),
followed by the S type (-30%). This finding has a
significant impact on our race to develop an ideal vaccine,
since the vaccine candidate has to target both strains to
be considered effective. At present, the genetic
differences between the L and S types are very small and
may not affect the immune response. However, we can
expect further genetic variations in the coming days that
could lead to the emergence of new strains. mask and
practice cough hygiene. Caregivers should be asked to
wear a surgical mask when in the same room as patient
and use hand hygiene every 15-20 min.

The greatest risk in COVID-19 is transmission to

healthcare workers. In the SARS outbreak of 2002, 21% of
those affected were healthcare workers. Till date, almost
1500 healthcare workers in China have been infected with
6 deaths. The doctor who first warned about the virus has
died too. It is important to protect healthcare workers to
ensure continuity of care and to prevent transmission of
infection to other patients. While COVID-19 transmits as a
droplet pathogen and is placed in Category B of infectious
agents (highly pathogenic H5N1 and SARS), by the China
National Health Commission, infection control measures
recommended are those for exponentially in other
countries including South Korea, Italy and Iran. Of those
infected, 20% are in critical condition, 25% have
recovered, and 3310 (3013 in China and 297 in other
countries) have died. India, which had reported only 3
cases till 2/3/2020, has also seen a sudden spurt in cases.
By 5/3/2020, 29 cases had been reported; mostly in Delhi,
Jaipur and Agra in Italian tourists and their contacts. One
case was reported in an Indian who traveled back from
Vienna and exposed a large number of school children in
a birthday party at a city hotel. Many of the contacts of
these cases have been quarantined.
These numbers are possibly an underestimate of the
infected and dead due to limitations of surveillance and
testing. Though the SARS-CoV-2 originated from bats, the
intermediary

Splits Tree phylogeny analysis.

In the unrooted phylogenetic tree of different

betacoronaviruses based on the S protein, virus
sequences from different subgenera grouped into
separate clusters. SARS-CoV-2 sequences from Wuhan
and other countries exhibited a close relationship and
appeared in a single cluster. The CoVs from the subgenus
Sarhecovirus appeared jointly in Splits Tree and divided
into three subclusters, namely, SARS-CoV-2, bat-SARS-
like- CoV (bat-SL-CoV), and SARS-CoV. In the case of
other subgenera, like Merhecovirus, all of the sequences
grouped in a single cluster, whereas in Embecovirus,
different species, comprised of canine respiratory CoVs,
bovine CoVs, equine CoVs, and human CoV strain
(OC43), grouped in a common cluster. Isolates in the
subgenera Nobecovorus and Hibecovirus were found to
be placed separately away from other reported SARS-
CoVs but shared a bat origin.

CURRENT WORLDWIDE SCENARIO OF SARS-CoV-2

This novel virus, SARS-CoV-2, comes under the
subgenus Sarbecovirus of the Orthocoronavirinae
subfamily and is entirely different from the viruses other
emerging viral diseases. Several therapeutic and
preventive strategies, including vaccines,
immunotherapeutics, and antiviral drugs, have been
exploited against the previous CoV outbreaks (SARS-CoV
and MERS-CoV). These valuable options have already
been evaluated for their potency, efficacy, and safety,
along with several other types of current research that will
fuel our search for ideal therapeutic agents against
COVID-19. The primary cause of the unavailability of
approved and commercial vaccines, drugs, and
therapeutics to counter the carlier SARS-CoV and MERS-
CoV seems to owe to the lesser attention of the
biomedicine and pharmaceutical companies, as these two
CoVs did not cause much havoc, global threat, and panic
like those posed by the SARS-CoV-2 pandemic.
Moreover, for such outbreak situations, the requirement
for vaccines and therapeutics/drugs exists only for a
limited period, until the outbreak is controlled. The
proportion of the human population infected with SARS-
CoV and MERS-CoV was also much lower across the
globe, failing to attract drug and vaccine manufacturers
and producers. Therefore, by the time an effective drug or
vaccine is designed against such disease outbreaks, the
virus would have been controlled by adopting appropriate
and strict
Practice Points from an Indian Perspective

At the time of writing this article, the risk of coronavirus in

India is extremely low. But that may change in the next
few weeks. Hence the following is recommended:

• Healthcare providers should take travel history of all

patients with respiratory symptoms, and any international
travel in the past 2 weeks as well as contact with sick
people who have travelled internationally.

• They should set up a system of triage of patients with

respiratory illness in the outpatient department and give
them a simple surgical mask to wear. They should use
surgical masks themselves.
themselves while examining such patients and practice
hand hygiene frequently.

. Suspected cases should be referred to government

designated centers for isolation and testing (in Mumbai, at
this time, it is Kasturba hospital). Commercial kits for
testing are not yet available in India.

• Patients admitted with severe

pneumonia and acute respiratory distress syndrome
should be evaluated for travel history and placed under
contact and droplet isolation. Regular decontamination of
surfaces should be done. They should be tested for
etiology using multiplex PCR panels if logistics permit and
if no pathogen is identified, refer the samples for testing
for SARS- CoV-2.
specimens, like bronchoalveolar lavage fluid. sputum,
nasal swabs, fibro bronchoscope brush biopsy specimens,
pharyngeal swabs, feces, and blood.

The presence of SARS-CoV-2 in fecal samples has posed

grave public health concerns. In addition to the direct
transmission mainly occurring via droplets of sneezing and
coughing, other routes, such as fecal excretion and
environmental and fomite contamination, are contributing
to SARS-CoV-2 transmission and spread. Fecal excretion
has also been documented for SARS-CoV and MERS-
CoV, along with the potential to stay viable in situations
aiding fecal-oral transmission. Thus, SARS-CoV-2 has
every possibility to be transmitted through this mode.
Fecal-oral transmission of SARS- CoV-2, particularly in
regions having low standards of hygiene and poor
sanitation, may have grave consequences with regard to
the high spread of this virus. Ethanol and disinfectants
containing chlorine or bleach are effective against
coronaviruses. Appropriate precautions need to be
followed strictly while handling the stools of patients
infected with SARS-CoV-2. Biowaste materials and
sewage from hospitals must be adequately disinfected,
treated, and disposed of properly. The significance of
frequent and good hand hygiene and the United States,
lorone dihydrochloride (tilorone), was previously found to
possess potent antiviral activity against MERS, Marburg,
Ebola, and Chikungunya viruses. Even though it had
broad-spectrum activity, it was neglected for an extended
period. Tilorone is another antiviral drug that might have
activity against SARS-CoV-2.

Remdesivir, a novel nucleotide analog prodrug, was

developed for treating Ebola virus disease (EVD), and it
was also found to inhibit the replication of SARS-CoV and
MERS-CoV in primary human airway epithelial cell culture
systems. Recently, in vitro study has proven that
remdesivir has better antiviral activity than lopinavir and
ritonavir. Further, in vivo studies conducted in mice also
identified that treatment with remdesivir improved
pulmonary function and reduced viral loads and lung
pathology both in prophylactic and therapeutic regimens
compared to lopinavir/ritonavir-IFN-7 treatment in MERS-
CoV infection. Remdesivir also inhibits a diverse range
zoonotic bat CoV, and prepandemic zoonotic CoV,
Remdesivir is also considered the only therapeutic drug
that significantly reduces pulmonary pathology. All these
findings indicate that remdesivir has to be further
evaluated for its respiratory infection (SARI) and
respiratory distress, shock or hypoxaemia. Patients with
SARI can be given conservative fluid therapy only when
there is no evidence of shock. Empiric antimicrobial
therapy must be started to manage SARI. For patients
with sepsis, antimicrobials must be administered within 1
hour of initial assessments. The WHO and CDC
recommend that glucocorticoids not be used in patients
with COVID-19 pneumonia except where there are other
indications (exacerbation of chronic obstructive pulmonary
disease)

Patients' clinical deterioration is closely observed with

SARI; however, rapidly progressive respiratory failure and
sepsis require immediate supportive care interventions
comprising quick use of neuromuscular blockade and
sedatives, hemodynamic management, nutritional support,
maintenance of blood glucose levels, prompt assessment
and treatment of nosocomial pneumonia, and prophylaxis
against deep venous thrombosis (DVT) and
gastrointestinal (GI) bleeding. Generally, such patients
give way to their primary illness to secondary
complications like sepsis or multiorgan system failure. To
assess the genetic variation of different SARS-
CoV-2 strains, the 2019 Novel Coronavirus Resource of
China National Center for Bioinformation aligned 77,801
genome sequences of SARS-CoV-2 detected glob- ally
and identified a total of 15,018 mutations, including 14,824
single-nucleotide polymorphisms (BIGD)". In the S protein,
four amino acid alterations, V483A, L4551, F456V and
G4765, are located near the binding interface in the RBD,
but their effects on binding to the host receptor are
unknown. The alteration D614G in the S1 subunit was
found far more frequently than other S variant sites, and it
is the marker of a major subclade of SARS-CoV-2 (clade
G). Since March 2020, SARS-CoV-2 variants with G614 in
the S protein have replaced the original D614 variants and
become the dominant form circulating globally. Compared
with the D614 variant, higher viral loads were found in
patients infected with the G614 variant, but clinical data
suggested no signif icant link between the D614G
alteration and disease severity. Pseudotyped viruses
carrying the S protein with G614 generated higher
infectious titres than viruses carrying the S protein with
D614, suggesting the altera- tion may have increased the
infectivity of SARS-CoV-2 (REF). However, the results of
in vitro experiments based on pseudovirus models may
not exactly reflect natural infection. This preliminary finding
should be validated by more studies using wild-type
SARS-CoV-2 variants to infect different target cells and
animal models. Whether this amino acid change enhanced
virus transmissibil- ity is also to be determined. Another
marker mutation for SARS-CoV-2 evolution is the single-
nucleotide the SARS-CoV. Environmental samples from
the Huanan sea food market also tested positive,
signifying that the virus originated from there. The number
of cases started increasing

exponentially, some of which did not have exposure to the

live animal market, suggestive of the fact that human-to-
human transmission was occurring. The first fatal case
was reported on 11th Jan 2020. The massive migration of
Chinese during the Chinese New Year fueled the
epidemic. Cases in other provinces of China, other
countries (Thailand, Japan and South Korea in quick
succession) were reported in people who were returning
from Wuhan. Transmission to healthcare workers caring
for patients was described on 20th Jan, 2020. By 23rd
January, the 11 million population of Wuhan was placed
under lock down with restrictions of entry and exit from the
region. Soon this lock down was glass opacities and sub
segmental consolidation. It is also abnormal in
asymptomatic patients/ patients with no clinical evidence
of lower respiratory tract involvement. In fact, abnormal CT
scans have been used to diagnose COVID-19 in suspect
cases with negative molecular diagnosis; many of these
patients had positive molecular tests on repeat testing.
Differential Diagnosis

The differential diagnosis includes all types of respiratory

viral infections [influenza, parainfluenza, respiratory
syncytial virus (RSV), adenovirus, human
metapneumovirus, non COVID- 19 coronavirus], atypical
organisms (mycoplasma, chlamydia) and bacterial
infections. It is not possible to differentiate COVID-19 from
these infections clinically or through routine variant group.
The receptor-binding gene region appears to be very
similar to that of the SARS- CoV and it is believed that the
same receptor would be used for cell entry.

Virion structure and its genome

Coronaviruses are structurally enveloped, belonging to the

positive-strand RNA viruses category that has the largest
known genomes of RNA. The structures of the coronavirus
are more spherical in shape, but their structure has the
potential to modify their morphology in response to
environmental conditions, being pleomorphic. The
capsular membrane which represents the outer envelope
usually has glycoprotein projection and covers the
nucleus, comprising a matrix protein containing a positive-
strand RNA. Since the structure possesses 5'-capped and
3'-polyadenylated ends, it remains identical to the cellular
mRNAs.18 The structure is comprised of hemagglutinin
esterase (HE) (present only in some beta-coronaviruses),
spike (S), small membrane (E), membrane (M) and
nucleocapsid (N). The envelope containing glycoprotein is
responsible for attachment to the host cell, which
possesses the primary anti-genic epitopes mainly those
consolidation. It is also abnormal in asymptomatic
patients/patients with no clinical evidence of lower
respiratory tract involvement. In fact, abnormal CT scans
have been used to diagnose COVID-19 in suspect cases
with negative molecular diagnosis; many of these patients
had positive molecular tests on repeat testing.

Differential Diagnosis

The differential diagnosis includes all types of respiratory

viral infections [influenza, parainfluenza, respiratory
syncytial virus (RSV), adenovirus, human
metapneumovirus, non COVID- 19 coronavirus], atypical
organisms (mycoplasma, chlamydia) and bacterial
infections. It is not possible to differentiate COVID-19 from
these infections clinically or through routine lab tests.
Therefore travel history becomes important. However, as
the epidemic spreads, the travel history
(using suitable animal models) should be conducted to
evaluate the risk of future epidemics. Presently. licensed
antiviral drugs or vaccines against SARS- CoV, MERS-
CoV, and SARS-CoV-2 are lacking. However, advances in
designing antiviral drugs and vaccines against several
other emerging diseases will help develop suitable
therapeutic agents against COVID-19 in a short time. Until
then, we must rely exclusively on various control and
prevention measures to prevent this new disease from
becoming a pandemic.
mice, and hDPP4-Tg mice (transgenic for expressing
hDPP4) for MERS-CoV infection. The CRISPR-Cas9
gene-editing tool has been used for inserting genomic
alterations in mice, making them susceptible to MERS-
CoV infection. Efforts are under way to recognize suitable
animal models for SARS-CoV2/COVID-19, identify the
receptor affinity of this virus, study pathology in
experimental animal models, and explore virus-specific
immune responses and protection studies, which together
would increase the pace of efforts being made for
developing potent vaccines and drugs to counter this
emerging virus. Cell lines, such as monkey epithelial cell
lines (LLC-MK2 and Vero-B4), goat lung cells, alpaca
kidney cells, dromedary umbilical cord cells, and
advanced ex vivo three-dimensional tracheobronchial
tissue, have been explored to study human CoVs (MERS-
CoV). Vero and Huh-7 cells (human liver cancer cells)
have been used for isolating SARS-CoV-2.

Recently, an experimental study with rhesus monkeys as

animal models revealed the absence of any viral loads in
nasopharyngeal and anal swabs, and no viral replication
was recorded in the primary tissues at a time interval of 5
days post-reinfection in reposed monkeys. The
subsequent

virological, radiological, and pathological developed for

rapid and colorimetric detection of this virus. RT-LAMP
serves as a simple, rapid, and sensitive diagnostic method
that does not require sophisticated equipment or skilled
personnel. An interactive web-based dashboard for
tracking SARS-CoV-2 in a real-time mode has been
designed. A smartphone-integrated home-based point- of-
care testing (POCT) tool, a paper-based POCT combined
with LAMP, is a useful point-of-care diagnostic. An Abbott
ID Now COVID-19 molecular POCT-based test, using
isothermal nucleic acid amplification technology, has been
designed as a point-of-care test for very rapid detection of
SARS-CoV-2 in just 5 min. A CRISPR-based SHERLOCK
(specific high-sensitivity enzymatic reporter unlocking)
diagnostic for rapid detection of SARS-CoV-2 without the
requirement of specialized instrumentation has been
reported to be very useful in the clinical diagnosis of
COVID-19. A CRISPR-Cas12-based lateral flow assay
also has been developed for rapid detection of SARS-
CoV-2. Artificial intelligence, by means of a three-
dimensional deep-learning model, has been developed for
sensitive and specific diagnosis of COVID-19 via CT
images.

Tracking and mapping of the rising incidence rates,

disease outbreaks, community spread,Laboratory testing
for coronavirus disease 2019 (COVID- 19) in suspected
human cases

The assessment of the patients with COVID-19 should be

based on the clinical features and also epidemiological
factors. The screening protocols must be prepared and
followed per the native context. Collecting and testing of
specimen samples from the suspected individual is
considered to be one of the main principles for controlling
and managing the outbreak of the disease in a country.
The suspected cases must be screened thoroughly in
order to detect the virus with the help of nucleic acid
amplification tests such as reverse transcription
polymerase chain reaction (RT- PCR). If a country or a
particular region does not have the facility to test the
specimens, the specimens of the suspected individual
should be sent to the nearest reference laboratories per
the list provided by WHO

It is also recommended that the suspected

patients be tested for the other respiratory

pathogens by performing the routine laboratory

investigation per the local guidelines, mainly to

differentiate from other viruses that include

influenza virus, parainfluenza virus, adenovirus,

respiratory syncytial virus, rhinovirus, human might be

lower. Further genetic analysis is required between SARS-
CoV-2 and different strains of SARS-CoV and SARS-like
(SL) CoVs to evaluate the possibility of repurposed
vaccines against COVID-19. This strategy will be helpful in
the scenario of an outbreak, since much time can be
saved, because preliminary evaluation, including in vitro
studies, already would be completed for such vaccine
candidates.

Multiepitope subunit vaccines can be considered a

promising preventive strategy against the ongoing COVID-
19 pandemic. In silico and advanced immunoinformatic
tools can be used to develop multiepitope subunit
vaccines. The vaccines that are engineered by this
technique can be further evaluated using docking studies
and, if found effective, then can be further evaluated in
animal models. Identifying epitopes that have the potential
to become a vaccine candidate is critical to developing an
effective vaccine against COVID-19. The
immunoinformatics approach has been used for
recognizing essential epitopes of cytotoxic T lymphocytes
and B cells from the surface glycoprotein of SARS-CoV-2.
Recently, a few epitopes have been recognized from the
SARS-CoV- 2 surface glycoprotein. The selected epitopes
explored targeting molecular dynamic simulations,
Inhibition of virus replication. Replication inhibitors include
remdesivir (GS-5734), favilavir (T-705), riba- virin,
lopinavir and ritonavir. Except for lopinavir and ritonavir,
which inhibit 3CLpro, the other three all target RdRp2.
Remdesivir has shown activity against SARS-CoV-2 in
vitro and in vivo128136. A clinical study revealed a lower
need for oxygen support in patients with COVID-19 (REF).
Preliminary results of the Adaptive COVID-19 Treatment
Trial (ACTT) clinical trial by the National Institute of Allergy
and Infectious Diseases (NIAID) reported that remdesivir
can shorten the recovery time in hospitalized adults with
COVID-19 by a couple days compared with placebo, but
the difference in mortality was not statistically significant.
The FDA has issued an emergency use authorization for
remdesivir for the treatment of hospitalized patients with
severe COVID-19. It is also the first approved option by
the European Union for treatment of adults and adoles
cents with pneumonia requiring supplemental oxygen.
Several international phase III clinical trials are continuing
to evaluate the safety and efficacy of remdesivir for

the treatment of COVID-19, Favilavir (T-705), which is an

antiviral drug developed in Japan to treat influenza, has
been approved in China, Russia and India for the
treatment of COVID-19. A clinical study in China showed
that favilavir significantly reduced the signs of improved
disease signs on chest imaging and shortened the time to
viral clearance". A preliminary report in Japan showed
rates of clinical improvement of 73.8% and 87.8% from the
start of favilavir therapy in patients with mild COVID-19 at
7 and 14 days, respectively, and 40.1% and 60.3% in
patients with severe COVID-19 at 7 and 14 days
respectively. However, this study did not include a control
arm, and most of the trials of favilavir were based on a
small sample size. For more reliable assessment of the
effectiveness of favilavir for treating COVID-19, large-
scale randomized controlled trials should be conducted.

There is an increase in the outbreak of this virus through

human-to-human

transmission, with the fact that it has become widespread

around the globe. This confirms the fact similar to the
previous epidemics, including SARS and MERS, that this
coronavirus exhibited potential human-to-human
transmission, as it was recently declared a pandemic by
WHO.26

Respiratory droplets are the major carrier for coronavirus

transmission. Such droplets can either stay in the nose or
mouth or enter the lungs via the inhaled air. Currently, it is
known that COVID-19's transmission from one person to
another also occurs through touching either an infected
surface or even an object. With the current scant
awareness of the transmission systems however, airborne
safety measures with a high-risk procedure have been
proposed in many countries. Transmission levels, or the
rates from one person to another, reported differ by both
location and interaction with involvement in infection
control. It is stated that even asymptomatic individuals or
those individuals in their incubation period can act as
carrier of SARS-CoV2.27, 28 With the data and evidence
provided by the CDC, the usual incubation period is
probably 3 to 7 days, sometimes being prolonged up to
even 2 weeks, and the typical symptom occurrence
virological, radiological, and

pathological

observations indicated that the monkeys with reexposure

had no recurrence of COVID-19, like the SARS-CoV-2-
infected monkeys without rechallenge. These findings
suggest that primary infection with SARS-CoV-2 could
protect from later exposures to the virus, which could help
in defining disease prognosis and crucial inferences for
designing and developing potent vaccines against COVID-
19.

PREVENTION, CONTROL, AND MANAGEMENT

In contrast to their response to the 2002 SARS outbreak,

China has shown immense political openness in reporting
the COVID-19 outbreak promptly. They have also
performed rapid sequencing of COVID-19 at multiple
levels and shared the findings globally within days of
identifying the novel virus. The move made by China
opened a new chapter in global health security and
diplomacy. Even though complete lockdown was declared
following the COVID-19 outbreak in Wuhan, the large-
scale movement of people has resulted in a radiating
spread of infections in the surrounding provinces as well
as to several other countries. Large-scale screening
programs might prevailing chronic medical conditions such
as lung disease, heart failure, cancer, cerebrovascular
disease, renal disease, diabetes, liver disease and
immunocompromising conditions and pregnancy are risk
factors for developing severe illness. Management
includes implementation of prevention and control
measures and supportive therapy to manage the
complications, together with advanced organ support.

Corticosteroids must be avoided unless specified for

chronic obstructive pulmonary disease exacerbation or
septic shock, as it is likely to prolong viral replication as
detected in MERS-CoV patients.

12 EARLY SUPPORTIVE THERAPY AND MONITORING

Management of patients with suspected or documented

COVID-19 consists of ensuring appropriate infection
control and supportive care. WHO and the CDC posted
clinical guidance for COVID-19

Immediate therapy of add-on oxygen must be started for

patients with severe acute respiratory infection (SARI) and
respiratory snakes, and various other wild animals (20, 30,
79, 93, 124, 125, 287). Coronavirus infection is linked to
different kinds of clinical manifestations, varying from
enteritis in cows and pigs, upper respiratory disease in
chickens, and fatal respiratory infections in humans.

Among the CoV genera, Alphacoronavirus and

Betacoronavirus infect mammals, while
Gammacoronavirus and Deltacoronavirus mainly infect
birds, fishes, and, sometimes, mammals. Several novel
coronaviruses that come under the genus
Deltacoronavirus have been discovered in the past from
birds, like Wigeon coronavirus HKU20, Bulbul coronavirus
HKU11, Munia coronavirus HKU13, white-eye coronavirus
HKU16, night-heron coronavirus HKU19, and common
moorhen coronavirus HKU21, as well as from pigs
(porcine coronavirus HKU15). Transmissible
gastroenteritis virus (TGEV), porcine epidemic diarrhea
virus (PEDV), and porcine hemagglutinating
encephalomyelitis virus (PHEV) are some of the
coronaviruses of swine. Among them, TGEV and PEDV
are responsible for causing severe gastroenteritis in young
piglets with noteworthy morbidity and mortality. Infection
with PHEV also causes enteric infection but can cause
encephalitis due to its ability to infect the nervous dogs
have now sincerimumy, wame the chicken, ducks, and
pigs are not at all susceptible to SARS- CoV-2.

Similarly, the National Veterinary Services Laboratories of

the USDA have reported COVID-19 in tigers and lions that
exhibited respiratory signs like dry cough and wheezing.
The zoo animals are suspected to have been infected by
an asymptomatic zookeeper. The total number of COVID-
19- positive cases in human beings is increasing at a high
rate, thereby creating ideal conditions for viral spillover to
other species, such as pigs. The evidence obtained from
SARS-CoV suggests that pigs can get infected with
SARS-CoV-2. However, experimental inoculation with
SARS-CoV-2 failed to infect pigs.

Further studies are required to identify the possible animal

reservoirs of SARS-CoV-2 and the seasonal variation in
the circulation of these viruses in the animal population.
Research collaboration between human and animal health
sectors is becoming a necessity to evaluate and identify
the possible risk factors of transmission between animals
and humans. Such cooperation will help to devise efficient
strategies for the management of emerging zoonotic
diseases. prevent further spread of disease at mass
gatherings, functions remain canceled in the affected
cities, and persons are asked to work from home. Hence,
it is a relief that the current outbreak of COVID-19 infection
can be brought under control with the adoption of strategic
preventive and control measures along with the early
isolation of subsequent cases in the coming days. Studies
also report that since air traffic between China and African
countries increased many times over in the decade after
the SARS outbreak. African countries need to be vigilant
to prevent the spread of novel coronavirus in Africa. Due
to fear of virus spread, Wuhan City was completely shut
down. The immediate control of the ongoing COVID-19
outbreaks appears a mammoth task, especially for
developing countries, due to their inability to allocate
quarantine stations that could screen infected individuals'
movements. Such underdeveloped countries should divert
their resources and energy to enforcing the primary level
of preventive measures, like controlling the entry of
individuals from China or countries where the disease has
flared up, isolating the infected individuals, and
quarantining individuals with suspected infection. Most of
the sub-Saharan African countries have a fragile health
system that can be prevent further spread of disease at
mass gatherings, functions remain canceled in the
affected cities, and persons are asked to work from home.
Hence, it is a relief that the current outbreak of COVID-19
infection can be brought under control with the adoption of
strategic preventive and control measures along with the
early isolation of subsequent cases in the coming days.
Studies also report that since air traffic between China and
African countries increased many times over in the decade
after the SARS outbreak. African countries need to be
vigilant to prevent the spread of novel coronavirus in
Africa. Due to fear of virus spread, Wuhan City was
completely shut down. The immediate control of the
ongoing COVID-19 outbreaks appears a mammoth task,
especially for developing countries, due to their inability to
allocate quarantine stations that could screen infected
individuals' movements. Such underdeveloped countries
should divert their resources and energy to enforcing the
primary level of preventive measures, like controlling the
entry of individuals from China or countries where the
disease has flared up, isolating the infected individuals,
and quarantining individuals with suspected infection.
There is a new public health crises threatening the world
with the emergence and spread of 2019 novel coronavirus
(2019-nCoV) or the severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2). The virus originated in bats
and was transmitted to humans through yet unknown
intermediary animals in Wuhan, Hubei province, China in
December 2019. There have been around 96,000 reported
cases of coronavirus disease 2019 (COVID-2019) and
3300 reported deaths to date (05/03/2020). The disease is
transmitted by inhalation or contact with infected droplets
and the incubation period ranges from 2 to 14 d. The
symptoms are usually fever, cough, sore throat,
breathlessness, fatigue, malaise among others. The
disease is mild in most people; in some (usually the
elderly and those with

comorbiditiae) specifically in the respiratory tract will help

to reduce virus-triggered immune pathologies in COVID-
19. The later stages of coronavirus- induced inflammatory
cascades are characterized by the release of
proinflammatory interleukin-1 (IL-1) family members, such
as IL-1 and IL-33. Hence, there exists a possibility that the
inflammation associated with coronavirus can be inhibited
by utilizing anti-inflammatory cytokines that belong to the
IL-1 family. It has also been suggested that the actin
protein is the host factor that is involved in cell entry and
pathogenesis of SARS-CoV-2. Hence, those drugs that
modulate the biological activity of this protein, like
ibuprofen, might have some therapeutic application in
managing the discase. The plasma angiotensin 2 level
was found to be markedly elevated in COVID-19 infection
and was correlated with viral load and lung injury. Hence,
drugs that block angiotensin receptors may have potential
for treating COVID-19 infection. A scientist from Germany,
named Rolf Hilgenfeld, has been working on the
identification of drugs for the treatment of coronaviral
infection since the time of the first SARS outbreak.

The SARS-CoV $2 subunit has a significant function in

mediating virus fusion that provides entry into the host cell.
Heptad repeat 1 (HRI) and heptad out on the isolated virus
confirmed that there is a potential risk for the reemergence
of SARS-CoV infection from the viruses that are currently
circulating in the bat population.

CLINICAL PATHOLOGY OF SARS-CoV-2 (COVID-19)

The disease caused by SARS-CoV-2 is also named

severe specific contagious pneumonia (SSCP), Wuhan
pneumonia, and, recently, COVID- 19 (110). Compared to
SARS-CoV, SARS-CoV-2 has less severe pathogenesis
but has superior transmission capability, as evidenced by
the rapidly increasing number of COVID-19 cases (111).
The incubation period of SARS-CoV-2 in familial clusters
was found to be 3 to 6 days. The mean incubation period
of COVID-19 was found to be 6.4. days, ranging from 2.1
to 11.1 days. Among an early affected group of 425
patients, 59 years was the median age, of which more
males were affected. Similar to SARS and MERS, the
severity of this nCoV is high in age groups above 50
years. Symptoms of COVID-19 include fever, cough.
myalgia or fatigue, and, less commonly, headache,
hemoptysis, and diarrhea. Compared to the SARS-CoV-2-
infected patients in Wuhan during traditional Chinese
medicine (TCM). Therefore, the handling of bats for
trading purposes poses a considerable risk of transmitting
zoonotic Cov epidemics.

Due to the possible role played by farm and wild animals

in SARS-CoV-2 infection, the WHO, in their novel
coronavirus (COVID-19) situation report, recommended
the avoidance of unprotected contact with both farm and
wild animals. The live- animal markets, like the one in
Guangdong, China. provides a setting for animal
coronaviruses to amplify and to be transmitted to new
hosts, like humans. Such markets can be considered a
critical place for the origin of novel zoonotic discases and
have enormous public health significance in the event of
an outbreak. Bats are the reservoirs for several viruses;
hence, the role of bats in the present outbreak cannot be
ruled out. In a qualitative study conducted for evaluating
the zoonotic risk factors among rural communities of
southern China, the frequent human-animal interactions
along with the low levels of environmental biosecurity were
identified as significant risks for the emergence of zoonotic
disease in local communities.

The comprehensive sequence analysis of the Initially, the

epicenter of the SARS-CoV-2 pandemic was China, which
reported a significant number of deaths associated with
COVID-19, with 84,458 laboratory-confirmed cases and
4,644 deaths as of 13 May 2020. As of 13 May 2020.
SARS-CoV-2 confirmed cases have been reported in
more than 210 countries apart from China(WHO Situation
Report 114). COVID-19 has been reported on all
continents except Antarctica. For many weeks, Italy was
the focus of concerns regarding the large number of
cases, with 221,216 cases and 30,911 deaths, but now,
the United States is the country with the largest number of
cases, 1,322,054, and 79,634 deaths. Now, the United
Kingdom has even more cases (226,4671) and deaths
(32,692) than Italy. A John Hopkins University web
platform has provided daily updates on the basic
epidemiology of the COVID-19 outbreak viruses in nasal
washes, saliva, urine and faeces for up to 8 days after
infection, and a few naive ferrets with only indirect contact
were positive for viral RNA, suggest- ing airborne
transmission". In addition, transmission of the virus
through the ocular surface and prolonged presence of
SARS-CoV-2 viral RNA in faucal samples were also
documented. Coronaviruses can persist on inanimate
surfaces for days, which could also be the case for SARS-
CoV-2 and could pose a prolonged risk of infection".
These findings explain the rapid geographic spread of
COVID-19, and public health interventions to reduce
transmission will provide benefit to mitigate the epidemic,
as has proved successful in China and several other
countries, such as South Korea

Diagnosis

Early diagnosis is crucial for controlling the spread of

COVID-19. Molecular detection of SARS-CoV-2 nucleic
acid is the gold standard. Many viral nucleic acid detec-
tion kits targeting ORF1b (including RdRp), N, E or S
genes are commercially available. The detection time
ranges from several minutes to hours depending on the
technology,10,10-. The molecular detection can be
affected by many factors. Although SARS-CoV-2 has been
detected from a variety of respiratory sources, including
throat swabs, posterior oropharyngeal saliva,
nasopharyngeal swabs, sputum and bronchial fluid. the
viral load is higher in lower respiratory tract sam ples. In
addition, viral nucleic acid was also found in samples from
the intestinal tract or blood even when respiratory samples
were negative. Lastly, viral load may already drop from its
peak level on disease onset. Accordingly, false negatives
can be common when oral swabs and used, and so
multiple detection methods should be adopted to confirm a
COVID-19 diagnosis. Other detection methods were there-
fore used to overcome this problem. Chest CT was used
to quickly identify a patient when the capacity of molecular
detection was overloaded in Wuhan. Patients transmission
risk. Considering the zoonotic links associated with SARS-
CoV-2, the One Health approach may play a vital role in
the prevention and control measures being followed to
restrain this pandemic virus. The substantial importation of
COVID-19 presymptomatic cases from Wuhan has
resulted in independent, self- sustaining outbreaks across
major cities both within the country and across the globe.
The majority of Chinese cities are now facing localized
outbreaks of COVID-19. Hence, deploying efficient public
health interventions might help to cut the spread of this
virus globally.

The occurrence of COVID-19 infection on several cruise

ships gave us a preliminary idea regarding the
transmission pattern of the disease. Cruise ships act as a
closed environment and provide an ideal setting for the
occurrence of respiratory disease outbreaks. Such a
situation poses a significant threat to travelers, since
people from different countries are on board, which favors
the introduction of the pathogen. Although nearly 30 cruise
ships from different countries have been found harboring
COVID-19 infection, the major cruise ships that were
involved in the COVID-19 outbreaks are the Diamond
Princess, Grand Princess, Celebrity Apex, and Ruby
Princess. The in asymptomatic patients. These
abnormalities progress from the initial focal unilateral to
diffuse bilateral ground-glass opacities and will further
progress to or coexist with lung consolidation changes
within 1 to 3 weeks. The role played by radiologists in the
current scenario is very important. Radiologists can help in
the early diagnosis of lung abnormalities associated with
COVID-19 pneumonia. They can also help in the
evaluation of disease severity, identifying its progression
to acute respiratory distress syndrome and the presence
of secondary bacterial infections. Even though chest CT is
considered an essential diagnostic tool for COVID-19, the
extensive use of CT for screening purposes in the
suspected individuals might be associated with a
disproportionate risk-benefit ratio due to increased
radiation exposure as well as increased risk of cross-
infection. Hence, the use of CT for early diagnosis of
SARS-CoV-2 infection in high-risk groups should be done
with great caution.
More recently, other advanced diagnostics have been
designed and developed for the detection of SARS-CoV-2
(345, 347, 350-352). A reverse amplification (RT-LAMP),
namely, iLACO, has been developed for rapid and
colorimetric detection of this

transcriptional loop-mediated isothermal adaptive

evolution, close monitoring of the viral mutations that
occur during subsequent human-to- human transmission
is warranted.

M Protein

The M protein is the most abundant viral protein present in

the virion particle, giving a definite shape to the viral
envelope. It binds to the nucleocapsid and acts as a
central organizer of coronavirus assembly. Coronavirus M
proteins are highly diverse in amino acid contents but
maintain overall structural similarity within different
general. The M protein has three transmembrane
domains, flanked by a short amino terminus outside the
virion and a long carboxy terminus inside the virion.
Overall, the viral scaffold is maintained by M-M interaction.
Of note, the M protein of SARS-CoV-2 does not have an
amino acid substitution compared to that of SARS-CoV.

E. Protein
The coronavirus E protein is the most enigmatic and
smallest of the major structural proteins. It plays a
multifunctional role in the pathogenesis. assembly, and
release of the virus. It is a small integral membrane
polypeptide that acts as a viroporin (ion channel). The
inactivation or polymorphism at nucleotide position 28,144,
which results in amino acid substitution of Ser for Lys at
residue 84 of the ORFS protein. Those variants with this
mutation make up a single subclade labelled as 'clade S
Currently, however, the available sequence data are not
sufficient to interpret the early global transmission his- tory
of the virus, and travel patterns, founder effects and public
health measures also strongly influence the spread of
particular lineages, irrespective of potential biological
differences between different virus variants.

Animal host and spillover

Bats are important natural hosts of alphacoronaviruses

and betacoronaviruses. The closest relative to SARS-
CoV-2 known to date is a bat coronavirus detected in
Rhinolophus affinis from Yunnan province, China, named
'RaTG13, whose full-length genome sequence is 96.2%
identical to that of SARS-CoV-2 (REF). This bat virus
shares more than 90% sequence identity with SARS-CoV-
2 in all ORFs throughout the genome, including the highly
variable S and ORF8 REF. Phylogenetic analysis confirms
that SARS-CoV-2 closely clusters with RaTG13. The high
genetic similarity between SARS-CoV-2 and RaTG13
supports the hypothesis that SARS-CoV-2 likely originated
from bats. Another related coronavirus has been reported
more recently in a Rhinolophus malayanus bat sampled in
Yunnan This novel hat virus denoted 'RmYN02'N Protein

The N protein of coronavirus is multipurpose. Among

several functions, it plays a role in complex formation with
the viral genome, facilitates M protein interaction needed
during virion assembly, and enhances the transcription
efficiency of the virus. It contains three highly conserved
and distinct domains, namely, an NTD, an RNA-binding
domain or a linker region (LKR), and a CTD. The NTD
binds with the 3' end of the viral genome. perhaps via
electrostatic interactions, and is highly diverged both in
length and sequence. The charged LKR is serine and
arginine rich and is also known as the SR (serine and
arginine) domain. The LKR is capable of direct interaction
with in vitro RNA interaction and is responsible for cell
signaling. It also modulates the antiviral response of the
host by working as an antagonist for interferon (IFN) and
RNA interference. Compared to that of SARS-CoV, the N
protein of SARS-CoV-2 possess five amino acid
mutations, where two are in the intrinsically dispersed
region (IDR; positions 25 and 26), one each in the NTD
(position 103), LKR (position 217), and CTD (position 334)
(16).

nsps and Accessory Proteins vitro antiviral potential of

FAD-approved drugs, V., ribavirin, penciclovir,
nitazoxanide, nafamostat, and chloroquine, tested in
comparison to remdesivir and favipiravir (broad-spectrum
antiviral drugs) revealed remdesivir and chloroquine to be
highly effective against SARS-CoV-2 infection in vitro.
Ribavirin. penciclovir. and favipiravir might not possess
noteworthy in vivo antiviral actions for SARS-CoV-2, since
higher concentrations of these nucleoside analogs are
needed in vitro to lessen the viral infection. Both
remdesivir and chloroquine are being used in humans to
treat other diseases, and such safer drugs can be
explored for assessing their effectiveness in COVID-19
patients.

Several therapeutic agents, such

as and lopinavir/ritonavir, chloroquine.

hydroxychloroquine, have been proposed for the clinical
management of COVID-19 (299). A molecular docking
study, conducted in the RNA- dependent RNA polymerase
(RdRp) of SARS-CoV-2 using different commercially
available antipolymerase drugs, identified that drugs such
as ribavirin, remdesivir, galidesivir, tenofovir, and
sofosbuvir bind RdRp tightly, indicating their vast potential
to be used against COVID-19. A broad-spectrum antiviral
drug that was developed in the United States, tilorone
dihydrochloride (tilorone),nsps and Accessory Proteins

Besides the important structural proteins, the SARS-CoV-

2 genome contains 15 nsps, nspl to nsp10 and nsp12 to
nsp16, and 8 accessory proteins (3a. 3b, p6. 7a. 7b, 8b,
9b, and ORF14). All these proteins play a specific role in
viral replication. Unlike the accessory proteins of SARS-
CoV. SARS-CoV-2 does not contain 8a protein and has a
longer 8b and shorter 3b protein. The nsp7, nsp13,
envelope, matrix, and p6 and 8b accessory proteins have
not been detected with any amino acid substitutions
compared to the sequences of other coronaviruses.

SARS-COV-2

understanding of the lung inflammation associated with

this infection.
SARS is a viral respiratory disease caused by a formerly
unrecognized animal CoV that originated from the wet
markets in southern China after adapting to the human
host, thereby enabling transmission between humans. The
SARS outbreak reported in 2002 to 2003 had 8,098
confirmed cases with 774 total deaths (9.6%). The
outbreak severely affected the Asia Pacific region,
especially mainland China. Even though the case fatality
rate (CFR) of SARS-CoV-2 (COVID-19) is lower than that
of SARS-COV, there exists a severe concern linked to this
outbreak due to its epidemiological similarity to influenza
viruses. This can fail the public health system, resulting in
a pandemic.

MERS is another respiratory disease that was first

reported in Saudi Arabia during the year 2012. The
disease was found to have a CFR of around 35%. The
analysis of available data sets suggests that the
incubation period of SARS-CoV-2, SARS-CoV, and
MERS-CoV is in almost the same range. The longest
predicted incubation time of SARS-CoV-2 is 14 days.
Hence, suspected individuals are isolated for 14 days to
avoid the risk of further spread. Even though a high
similarity has been reported
respiratory syncytial virus, rhinovirus, human
metapneumovirus and SARS coronavirus. It is advisable
to distinguish COVID-19 from other pneumonias such as
mycoplasma pneumonia, chlamydia pneumonia and
bacterial pneumonia,Several published pieces of literature
based on the novel coronavirus reported in China declared
that stool and blood samples can also collected from the
suspected persons in order to detect the virus. However,
respiratory samples show better viability in identifying the
virus, in comparison with the other specimens.

Nucleic acid amplification tests (NAAT) for COVID-19 virus

The gold standard method of confirming the suspected

cases of COVID-19 is carried out by detecting the unique
sequences of virus RNA through reverse transcription
polymerase chain reaction (RT-PCR) along with nucleic
acid sequencing if needed. The various genes of virus
identified so far include N, E, S (N: nucleocapsid protein,
E: envelope protein gene, 5: spike protein gene) and
RdRP genes (RNA- dependent RNA polymerase gene),
All of these therapeutic approaches have revealed both in
vitro and in vivo anti-CoV potential. Although in vitro
research carried out with these therapeutics showed
efficacy, most need appropriate support from randomized
animal or human trials. Therefore, they might be of limited
applicability and require trials against SARS-CoV-2 to gain
practical usefulness. The binding of SARS-CoV-2 with
ACE2 leads to the exacerbation of pneumonia as a
consequence of the imbalance in the renin- angiotensin
system (RAS). The virus-induced pulmonary inflammatory
responses may be reduced by the administration of ACE
inhibitors (ACEI) and angiotensin type-1 receptor (ATIR).

Several investigations have suggested the use of small-

molecule inhibitors for the potential control of SARS-CoV
infections. Drugs of the FDA-approved compound library
were screened to identify four small-molecule inhibitors of
MERS-CoV (chlorpromazine, chloroquine, loperamide,
and lopinavir) that inhibited viral replication. These
compounds also hinder SARS-CoV and human CoVs.
Therapeutic strategies involving the use of specific
antibodies or compounds that neutralize cytokines and
their receptors will help to restrain the host inflammatory
responses. Such drugs acting specifically in the
respiratory tract will help to severe illness, to minimise the
risk of exposure to COVID-19 during outbreaks.

VACCINES

The strange coronavirus outbreak in the Chinese city of

Wuhan, now termed COVID-19, and its rapid
transmission, threatens people around the world. Because
of its pandemic nature, the National Institutes of Health
(NIH) and pharmaceutical companies are involved in the
development of COVID-19 vaccines. Xu Nanping, China's
vice-minister of science and technology, announced that
the first vaccine is expected to be ready for clinical trials in
China at the end of April 2020.There is no approved
vaccine and treatment for COVID-19 infections.

Vaccine development is sponsored and supported by the

Biomedical Advanced Research and Development
Authority (BARDA), a component of the Office of the
Assistant Secretary for Preparedness and Response
(ASPR). Sanofi will use its egg-free, recombinant DNA
technology to produce an exact genetic match to proteins
of the virus, major problem associated with this diagnostic
kit is that it works only when the test subject has an active
infection, limiting its use to the earlier stages of infection.
Several laboratories around the world are currently
developing antibody-based diagnostic tests against SARS-
CoV-2.

Chest CT is an ideal diagnostic tool for identifying viral

pneumonia. The sensitivity of chest CT is far superior to
that of X-ray screening. The chest CT findings associated
with COVID-19- infected patients include characteristic
patchy infiltration that later progresses to ground-glass
opacities. Early manifestations of COVID-19 pneumonia
might not be evident in X-ray chest radiography. In such
situations, a chest CT examination can be performed, as it
is considered highly specific for COVID-19 pneumonia.
Those patients having COVID-19 pneumonia will exhibit
the typical ground-glass opacity in their chest CT images.
The patients infected with COVID-19 had elevated plasma
angiotensin 2 levels. The level of angiotensin 2 was found
to be linearly associated with viral load and lung injury,
indicating its potential as a diagnostic biomarker. The
chest CT imaging abnormalities associated with COVID-
19 pneumonia have also been observed even in
asymptomatic patients. These abnormalities of plasma
cytokines, which suggests an immunopathological process
caused by a cytokine storm. In this cohort of patient,
around 2.3% people died within a median time of 16 days
from disease onset. Men older than 68 years had a higher
risk of respiratory failure, acute cardiac injury and heart
failure that led to death, regardless of a history of
cardiovascular disease". Most patients recovered enough
to be released from hospital in 2 weeks.

Early transmission of SARS-CoV-2 in Wuhan in December

2019 was initially linked to the Huanan Seafood Wholesale
Market, and it was suggested as the source of the
outbreak. However, community transmission might have
happened before that". Later, ongoing human-to-human
transmission propagated the outbreak. It is generally
accepted that SARS-CoV-2 is more transmissible than
SARS-CoV and MERS-CoV; however, determination of an
accurate reproduction number (RO) for COVID-19 is not
possible yet, as many asymptomatic infections cannot be
accurately accounted for at this stage. An estimated RO of
2.5 (ranging from 1.8 to 3.6) has been proposed for
SARS-CoV-2 recently, compared with 2.0-3.0 for SARS-
CoV. Notably, most of the SARS-CoV-2 human-to-human
transmission early in China occurred in family clusters,
and in other countries large outbreaks also happened in
other set- tings, such as migrant worker communities,
slaughter- houses and meat packing plants, indicating the
necessity of isolating infected people 1251. Nosocomial
transmission was not the main source of transmission in
China because of the implementation of infection control
measures in clinical settings. By contrast, a high risk of
nosocomial transmission was reported in some other
position origin of SARS-COV-Z: Made at disease
transmission are not yet identified. Analysis of the initial
cluster of infections suggests that the infected individuals
had a common exposure point, a seafood market in
Wuhan, Hubei Province, China. The restaurants of this
market are well-known for providing different types of wild
animals for human consumption. The Huanan South
China Seafood Market also sells live animals, such as
poultry, bats, snakes, and marmots. This might be the
point where zoonotic (animal-to- human) transmission
occurred. Although SARS-CoV-2 is alleged to have
originated from an animal host (zoonotic origin) with
further human-to- human transmission, the likelihood of
foodborne transmission should be ruled out with further
investigations, since it is a latent possibility. Additionally,
other potential and expected routes would be associated
with transmission, as in other respiratory viruses, by direct
contact, such as shaking contaminated hands, or by direct
contact with contaminated surfaces. Still, whether blood
transfusion and organ transplantation, as well as
transplacental and perinatal routes, are possible routes for
SARS-CoV-2 transmission needs to be determined. and
other SARS-CoVs. Using sequences of five conserved
replicative domains in pplab (3C-like protease (3CL pro),
nidovirus RNA-dependent RNA polymerase (RdRp)-
associated nucleotidyltransferase (NIRAN), RdRp, zinc-
binding domain (ZBD) and HEL1), the Coronaviridae
Study Group of the International Committee on Taxonomy
of Viruses estimated the pairwise patristic distances
between SARS-CoV-2 and known coronaviruses, and
assigned SARS-CoV-2 to the existing species SARS-CoV.
Although phyloge- netically related, SARS-CoV-2 is
distinct from all other coronaviruses from bats and
pangolins in this species.

The SARS-CoV-2 S protein has a full size of 1,273 amino

acids, longer than that of SARS-CoV (1,255 amino acids)
and known bat SARS-CoVs (1,245-1,269 amino acids). It
is distinct from the S proteins of most members in the
subgenus Sarbecovirus, sharing amino acid sequence
similarities of 76.7- 77.0% with SARS-CoVs from civets
and humans, the initial stages of the outbreak, only mild
symptoms were noticed in those patients that are infected
by human-to-human transmission.

The initial trends suggested that the mortality associated

with COVID-19 was less than that of previous outbreaks of
SARS. The updates obtained from countries like China,
Japan, Thailand. and South Korea indicated that the
COVID-19 patients had relatively mild manifestations
compared to those with SARS and MERS. Regardless of
the coronavirus type, immune cells, like mast cells, that
are present in the submucosa of the respiratory tract and
nasal cavity are considered the primary barrier against this
virus. Advanced in-depth analysis of the genome has
identified 380 amino acid substitutions between the amino
acid sequences of SARS-CoV-2 and the SARS/SARS-like
coronaviruses. These differences in the amino acid
sequences might have contributed to the difference in the
pathogenic divergence of SARS-CoV-2. Further research
is required to evaluate the possible differences in tropism,
pathogenesis, and transmission of this novel agent
associated with this change in the amino acid sequence.
With the current outbreak of COVID-19, there is an
expectancy of a significant increase in the number of
published studies about this emerging coronavirus, as
occurred primary anti-genic epitopes mainly those
recognised by neutralising antibodies. The spike S-protein
being in a spike form is subjected to a structural
rearrangement process so that fusing the outer membrane
of the virus with the host- cell membrane becomes
easier,19,20 Recent SARS-CoV work has also shown that
the membrane exopeptidase ACE enzyme (angiotensin-
converting enzyme) functions as a COVID-19 receptor to
enter the human cell.

That remdesivir has to be further evaluated for its efficacy

in the treatment of COVID-19 infection in humans. The
broad-spectrum activity exhibited by remdesivir will help
control the spread of disease in the event of a new
coronavirus outbreak.

Chloroquine is an antimalarial drug known to possess

antiviral activity due to its ability to block virus-cell fusion
by raising the endosomal pH necessary for fusion. It also
interferes with virus- receptor binding by interfering with
the terminal glycosylation of SARS-CoV cellular receptors,
such as ACE2. In a recent multicenter clinical trial that was
conducted in China, chloroquine phosphate was found to
exhibit both efficacy and safety in the therapeutic
management of SARS-CoV-2-associated pneumonia. This
drug is already included in the treatment guidelines issued
by the National Health Commission of the People's
Republic of China. The preliminary clinical trials using
hydroxychloroquine, another aminoquinoline drug. gave
promising results. The COVID-19 patients received 600
mg of hydroxychloroquine daily along with azithromycin as
a single-arm protocol. This protocol was found to be
associated with a noteworthy reduction in viral load.
Finally, it resulted in a complete cure; however, the study
comprised a small population and, hence, the and ritonavir
had little therapeutic benefit in patients with COVID-19, but
appeared more effective when used in combination with
other drugs, including ribavirin and interferon beta-lb. The
Randomized Evaluation of COVID-19 Therapy
(RECOVERY) trial, a national clinical trial programme in
the UK, has stopped treatment with lopinavir and ritonavir
as no significant beneficial effect was observed in a
randomized trial established in March 2020 with a total of
1,596 patients. Nevertheless, having proven uses against
other viral pathogens can be employed for SARS-CoV-2-
infected patients. These possess benefits of easy
accessibility and recognized pharmacokinetic and
pharmacodynamic activities, stability, doses, and side
effects. Repurposed drugs have been studied for treating
CoV infections, like lopinavir/ritonavir, and interferon-1ẞ
revealed in vitro anti-MERS-CoV action. The in vivo
experiment carried out in the nonhuman primate model of
common marmosets treated with lopinavir/ritonavir and
interferon beta showed superior protective results in
treated animals than in the untreated ones. A combination
of these drugs is being evaluated to treat MERS in
humans (MIRACLE trial). These two protease inhibitors
(lopinavir and ritonavir), in combination with ribavirin, gave
encouraging clinical outcomes in SARS patients,
suggesting their therapeutic values. However, in the
current scenario, due to the lack of specific therapeutic
agents against SARS- CoV-2, hospitalized patients
confirmed for the disease are given supportive care, like
oxygen and fluid therapy, along with antibiotic therapy for
managing secondary bacterial infections. Patients with
novel coronavirus or COVID-19 pneumonia who are
mechanically ventilated often require sedatives,
analgesics, and even muscle Based on molecular
characterization, SARS- CoV-2 is considered a new
Betacoronavirus belonging to the subgenus Sarbecovirus.
A few other critical zoonotic viruses (MERS-related CoV
and SARS-related CoV) belong to the same genus.
However, SARS-CoV-2 was identified as a distinct virus
based on the percent identity with other Betacoronavirus;
conserved open reading frame la/b (ORF1a/b) is below
90% identity. An overall 80% nucleotide identity was
observed between SARS-CoV-2 and the original SARS-
CoV, along with 89% identity with ZC45 and ZXC21
SARS- related CoVs of bats. In addition, 82% identity has
been observed between SARS-CoV-2 and human SARS-
CoV Tor2 and human SARS-CoV BJ01 2003. A sequence
identity of only 51.8% was observed between MERS-
related CoV and the recently emerged SARS-CoV-2.
Phylogenetic analysis of the structural genes also
revealed that SARS-CoV-2 is closer to bat SARS-related
CoV. Therefore, SARS-CoV-2 might have originated from
bats, while other amplifier hosts might have played a role
in disease transmission to humans. Of note, the other two
zoonotic CoVs (MERS-related CoV and SARS-related
CoV) also originated from bats.