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 [3]. Moreover, a four-residue motif in the RBM

of SARS-CoV-2 (amino acids 482-485:G-V-E-G) results in a more compact conformation of its

hACE2-binding ridge than in SARS-CoV and enables better contact with the N-terminal helix of

hACE2 (REFS). All the patients were either asymptomatic (9%) or had mild disease. Tackling this

epidemic is a long-term job which requires efforts of every individual, and international

collaborations by scientists, authorities and the public a polybasic cleavage site (RRAR), which

enables effective cleavage by furin and other proteases". 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" (FIG. Acute viral interstitial pneumonia and humoral and cellular immune

responses were observed. 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. CDC (Table 1) (258, 259) consolidation. The six functional open

reading frames (ORFs) are arranged in order from 5' to 3': replicase (ORFla/ORF1b), spike (S),

envelope (E), membrane (M) and nucleocapsid (N). All patients recovered with symptomatic

therapy and there were no deaths. Advanced in-depth analysis of the genome has identified 380

amino acid substitutions between the amino acid sequences of SARS-CoVv-2 and the

SARS/SARS-like coronaviruses. Immediately after the confirmation of viral etiology, the Chinese

virologists rapidly released the genomic sequence of SARS-CoV-2, which played a crucial role in
controlling the spread of this newly emerged novel coronavirus to other parts of the world (69).

4).

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 outbreak260. 4).

Currently, however, the available sequence data are not sufficient to interpret the early global

transmision history ofthe 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. Since March, while COVID-19 in China has become effectively

controlled, the case numbers in Europe, the USA and other regions have jumped sharply. The city

of Wuhan was shut down on 23 January, and all travel and transportation connecting the city was

blocked. In the following couple of weeks, all outdoor activities and gatherings were restricted,

and public facilities were dosed in most cities as well as in countryside". So far, no evidence has

shown that pangolins were directly involved in the emergence of SARSCoV-2. The SARS- CoV,

Transmission of SARS-CoV occurred mainly after illness onset and peaked following disease

severity, However, the SARS-CoV-2 viral load in upper respiratory tract samples was already

highest during the first week of symptoms, and thus the risk of pharyngeal virus shedding was very

high at the beginning of infection%. Except for lopinavir and ritonavir, which inhibit 3CLpro, the

other three all target RdRp2515 (FIG. 2). 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. By 23rd

January, the 11 million population of Wuhan was placed under lock down with restrictions of entry

and exit from the region. The neutralizing epitopes of these monoclonal antibodies also offer

important information for vaccine design. The outbreak of COVID-19 in China reached an
epidemic peak in February. (3a). Hence, deploying efficient public health interventions might help

to cut the spread of this virus globally.

ANIMAL HOST AND SPILLOVER

Bats are important natural hosts of alpha coronaviruses and beta coronaviruses. (5). A lying-down

conformation of the SARS-CoV-2 S protein may not be in favour of receptor binding but is helpful

for immune evasion". The possible origin of SARS-CoV-2 and the first mode of polymorphism at

nucleotide position 28,144, which results in amino acid substitution of Ser for Lys at residue 84 of

the ORF8 protein. The possibility of eross protection in CoVID-19 was comparing the S protein

sequences of SARS-CoV-2 evaluated by with that of SARS-CoV. Food and Drug

Administration (FDA) had granted 22 in vitro diagnostics Emergency Use Authorizations (EUAs),

including for the RT-

PCR diagnostic panel for the universal detection of SARS-like beta coronaviruses and specific

detection of SARS-CoV2, developed by the U.S. Many people are asymptomatic. 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 "). Cytokine storm syndrome causes acute respiratory distress

syndrome and respiratory failure, which is considered the main cause of death in patients with

COVID-19 (REFS0). and deaths. By contrast, a high risk of nosocomial transmission was reported

in some other. The pathogenesis of SARS-CoV-2 infection in humans manifests itself as mild

symptoms to severe respiratory failure. Regardless of the coronavirus type, immune cells, like

mast cels, that are present in the submucosa of the respiratory tract and nasal cavity are considered
the primary barrier against this virus (92). Virus may also be detected in the stool and in severe

cases, the blood. 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 (REF35). Beyond bats, pangolins

are another wildlife host probably linked with SARS-CoV-2. Biochemical data confirmed that the

structural features of the SARS-CoV-2 RBD has strengthened its hACE2 binding affinity

compared with that of SARS-CoV50,52.53. Similarly to other coronaviruses, SARS-CoV-2 needs

proteolytic processing of the S protein to activate the endocytic route. The USA is the country with

the largest number of cases so far. Although genetic evidence suggests that SARS-CoV-2 is a

natural virus that likely originated in animals, there is no conclusion yet about when and where the

virus first entered humans. 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 place, but the difference in mortality was not statistically significant, The FDA has

issued an emergency use authorization for rem desivir for the treatment of hospitalized patients

with severe COVID-19. 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). On 30 January, the WHO declared the novel
coronavirus outbreak a public health emergency of inter- national concern". It must be remembered

that the multiplex PCR panels currently available do not include the COVID-19. Intensive studies

on these virological profiles of SARS-CoV-2 will provide the basis for the development of

preventive and therapeutic strategies against COVID-19. 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. Replication inhibitors include remdesivir (GS-5734), favilavir (T-705), ribavirin,

lopinavir and ritonavir. The majority of Chinese cities are now facing localized outbreaks of

COVID-19 (231). 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 lower respiratory tracts. Moreover, continued genomic monitoring of SARS-

CoV-2 in new cases is needed worldwide, as it is important to promptly identify any mutation that

may result in phenotypic changes of the virus. In another study, the average reproductive number

of major problem associated with this diagnostic kit is that it works only when the test subject has

an active infection, limiting its associated earlier stages of infection. Commercial tests are also not

available at present. 3a). Convalescent plasma treatment is another potential adjunctive therapy for

COVID-19. 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 OVID-19. The recent increase in the

number of confirmed critically ill patients with COVID-19 has already surpassed the intensive

care supplies, limiting intensive care services to only a small portion of critically ill patients (67).

Before choosing the ideal therapeutic agent for the management of COVID-19, randomized

clinical control studies should be performed with a sufficient study population.

VACCINES

Vaccination is the most effective method for a long-term strategy for prevention and control of

COVID-19 in the future. 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. Canines

are also affected by CoVs that fall under different genera, namely, canine enteric coronavirus in

Alpha coronavirus and in Beta coronavirus, affecting the enteric and canine respiratory and

respiratory tract, respectively (129, 130). High mortality occurred especially when health-care

resources were overwhelmed. Multiple organ failure has also been reported in some COVID-19

cases 1365. Histopathological changes in patients with COVID-19 occur mainly in the lungs. 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 S1

subunit ofa corona-virus is further divided into two functional domains, an N-terminal domain and

a C-terminal domain. Structural and biochemical analyses identified a 211 amino acid region

(amino acids 319-529) at the S1 C-terminal domain of SARS-CoV-2 as the RBD, which has a key

role in virus entry and is the target of neutralizing antibodiess051 (FIG. The virus strains carried

by these two intermediate hosts were almost genetically identical to the corresponding viruses in

humans (more than 99% genome sequence identity)'.Despise an RBD that is virtually identical to

that of SARS-CoV-2, the pangolin coronaviruses known to date have no more than 92% genome

identity with SARS-CoV-2 (REF). 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 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 (121). Up to 30 March 2020, the U.S.

Later, ongoing human-to-human transmission propagated the outbreak". Most of the proteins

encoded by SARS-CoV-2 have a similar with COVID-19 showed typical features on initial CT,

including bilateral multilobar ground-glass opacities with a peripheral or posterior distribution1,

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"1, 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

retrospective studies16,120121, 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). (3d). A structural study suggested that the furin-

cleavage site can reduce the stability of SARS-CoV 2 S protein and facilitate the conformational

adaption that is required for the binding of the RBD to its receptor". These differences in the amino

acid sequences might have contributed to the difference in the pathogenic divergence of SARS-

CoV-2 (16). 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. The IFR was found to be in the range of 0.3% to 0.6%, which is comparable to that of a

previous Asian influenza pandemic (1957 to 1958) (73, 277). Notably, the reanalysis of the

COVID -19 pandemic curve from the initial cluster of cases pointed to considerable human-to-

human transmission. In comparison with the Guangdong strains, pangolin coronaviruses reported

from Guangxi are less similar to SARS-CoV-2, with 85.5% genome sequence identity", The

repeated occurrence of SARS-CoV-2-related coronavirus infections in pangolins from different

smuggling events suggests that these animals are possible hosts of the viruses. This property of the

RBD can be utilized for designing potential SARSCoV RBD-containing vaccines either by using

recombinant proteins or recombinant vectors that encode RBD (175). Compared to emerging

viruses like Ebola virus, avian H7N9, SARS-CoV, and MERS-CoV, SARS-CoV-2 has relatively

lower pathogenicity and moderate transmissibility (15). The risk of death among individuals

infected with COVID-19 was caleulated using the infection fatality risk (IFR). Researchers and

manufacturers are conducting large-scale clinical trials to evaluate various therapies for COVID-

19. They are very closely related to SARS-CoV-2, exhibiting 92.4% sequence similarity. Finally,

COVID-19 is challenging all human beings. Common laboratory findings include normal/low

white cell counts with elevated C reactive protein (CRP). Most of these SARS-CoV-2 non-

structural proteins have greater than 85% amino acid sequence identity with SARS-CoV25. The

phylogenetic analysis for the whole genome shows that SARS-CoV-2 is clustered with SARS-

CoV and SARS-related coronaviruses (SARSr-CoVs) found in bats, placing it in the subgenus

Sarbecovirus of the genus Beta coronavirus. The receptor-binding gene region (173, 174). On

binding to epithelial cells in the respiratory tract, SARS-CoV-2 starts replicating and migrating

down to the airways and enters alveolar epithelial cells in the lungs. The comparative analysis

confirmed that the variable residues were found concentrated on the SI subunit of S protein, an
important vaccine target of the virus (150). Recent studies reported specific monoclonal antibodies

neutralizing SARS-CoV-2 infection.

INHIBITION OF VIRUS

REPLICATION:

The massive migration of Chinese during the Chinese New Year fuelled 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. It has been shown that host proteases

participate in the cleavage of the S protein and activate the entry of SARS-CoV-2, including

transmembrane protease serine protease 2 (TMPRSS2), cathepsin L and furint"5455.

Environmental samples from the Huanan sea food market also tested positive, signifying that the

virus originated from there [7]. The virus spreads faster than its twn ancestors the SARS-CoV

residues for receptor binding (FIG). However, this individual early report cannot give a solid

answer to the origin of SARS-CoV-2 and contamination, and thus a false positive result cannot be

excluded. More so, future outbreaks of viruses and pathogens of zoonotic origin are likely to

continue. Therefore, apart from curbing this outbreak. Bovine coronaviruses (BoCoVs) are known

to infect several domestic and wild ruminants (126). The first fatal case was reported on 11th Jan

2020. Several laboratories around the world are currently developing antibody-based diagnostic

tests against SARS-CoV-2 (157). Chest CT is an ideal diagnostic tool for identifying viral

pneumonia. 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 require

sedatives, analgesics, and even muscle relaxation drugs to prevent ventilator-related lung injury

incoordination (122). The discovery of diverse bat coronaviruses closely related to SARS-CoV-2
suggests that bats are possible reservoirs of SARS-CoV-2 (RE.*"). Within this clade, SARS-CoV-

2 is grouped in a distinct lineage together with four horseshoe bat coronavirus isolates (RaTG13,

RmYN02,ZC45 and ZXC21) as well as novel coronaviruses recently identified in pangolins,

which group parallel to SARS-CoV in vitro and in vivo5- 135, Compared with convalescent

plasma, which has limited availability and cannot be amplified, monoclonal antibodies can be

developed in larger quantities to meet clinical requirements. As the epidemic progresses,

commercial tests comorbidities), it may progress to pneumonia, acute respiratory distress

syndrome (ARDS) and multi organ dysfunction. The vaccine has proved to be safe and induced

considerable humoral and cellular immune response in most recipients after a single

immunization', Another vectored vaccine, ChAdOxl, and other SARSr-CoVs (FIG). At present,

nucleic acid detection techniques, like RT-PCR, are considered an effective method for confirming

the diagnosis in clinical cases of COVID-19 (148). Those variants with this mutation make up a

single subclade labelled as clade S'3,34. The most common symptoms were fever (50%) and cough

(38%). Histopathology analyses showed bilateral diffused alveolar damage, hyaline membrane

formation, desquamation of pneumocytes and fibrin deposits in lungs of patients with severe

COVID-19. This might also have contributed to the increased case fatality rate observed in the

COVID-19 outbreak.

VIROLOGY:

Coronaviruses, a family of viruses within the nidoviruses superfamily, are further classified

according to their genera, alpha-, beta-, gamma- and delta coronaviruses (a, B, y- and 8-). Among

those, alpha and beta species are capable of contaminating only mammals, whereas the other two

genera can infect birds and could also infect mammals.15, 14 Two of these genera belong to human
coronaviruses (HCOVs): a coronaviruses, which comprise human coronavirus 229E (hcov229E)

and human coronavirus NL63 (hcovNL63), and B coronaviruses, which are human coronavirus

HKU1, human coronavirus OC43, MERS-COVV (known as Middle East respiratory syndrome

coronavirus) and SARSCov (referred to as severe acute respiratory syndrome coronavirus).

The severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is now named novel COVID-19

(coronavirus disease 2019). 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 (10, 133).

It was postulated that undocumented infections might account for 79% of documented cases owing

to the high transmissibility of the virus during mild disease or the asymptomatic period. 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 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 [8]. However, unlike bats, which carry coronaviruses healthily, the infected pangolins

showed clinical signs and histopathological changes, including interstitial pneumonia and

inflammatory cell infiltration in diverse organs". According to the COVID-19 dashboard of the

Center for System Science and Engineering at Johns Hopkins University, as of l11 August 2020,

was linked to a family member and 26 children had history of travel/residence to Hubei province

in China. In the following sections, we summarize potential therapeutics against SARS-CoV-2 on

the basis of published clinical data and experience. Using sequences of five conserved replicative

domains in pplab (3C-ike protease3CLpro), 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 too the existing species SARSr-CoV", Although phylogenetically 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 SARSr-CoVs (1,245-1,269 amino acids). Remdesivir has shown

activity against SARS-CoV-2 in vitro and in vivo2136, A clinical study revealed a lower need for

oxygen support in patients with COVID-19 (REF 137). Therefore travel history becomes

important. However, as the epidemic spreads, the travel history the initial stages of the outbreak,

only mild symptoms were noticed in those patients that are infected by human-to-human

transmission (14). The initial trends suggested that the mortality associated with COVID-19 was

less than that of previous outbreaks of SARS (101). The avail- able data are insufficient to interpret

pangolins as the intermediate host of SARSCoV-2. It is not possible to differentiate COVID-19

from these infections clinically or through routine lab tests. To address this highly controversial

issue, further retrospective investigations involving a larger number of banked samples from

patients, animals and environments need to be conducted worldwide with well-validated assays.

GENOMICS, PHYLOGENY AND TAXONOMY:

As a novel betacoronavirus, SARS-CoV-2 shares 79% genome sequence identity with SARS-

CoV and 50% with MERSCoV4, Its genome organization is shared with other betacoronaviruses.

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. 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 (126). A patient with COVID-19 spreads

viruses in liquid droplets during speech. On 11 February, the International Committee on

Taxonomy of Viruses named the novel coronavirus 'SARS-CoV-2, and the WHO named the

disease 'COVID-19 (REF"). In human ACE2-transgenic mice infected with SARS-CoV-2,

typical interstitial pneumonia was present, and viral antigens were observed mainly in the

bronchial epithelial cells, macrophages and alveolar epithelia. In China, vapor inhalation of

interferon-a is included in the COVID-19 treatment guideline’s, Clinical trials are ongoing across

the world to evaluate the efficacy of different therapies involving interferons, either alone or in

combination with other agents.

IMMUNOGLOBULIN

THERAPY:

An ideal therapeutic option suggested need to be. The U.S. for SARS-CoV-2 (COVID-19) is the

combination therapy comprised of MAbs and the drug remdesivir (COVID-19) (201). 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, length to the corresponding proteins

in SARS-CoV.

Of the four structural genes, SARS-CoV-2 shares more than 90% amino acid identity with SARS-

CoV except for the S gene, which diverges24, The replicase gene covers two thirds of the 5

genome, and encodes a large polyprotein (pplab),which is proteolytically cleaved into 16 non-

structural proteins that are involved in transcription and virus replication. Many different vaccine
platforms against SARS-CoV-2 are in development, the strategies of which include recombinant

vectors, DNA, mRNA in lipid nanoparticles, inactivated viruses, live attenuated viruses and

protein subunits-lo. The chest CT findings associated with COVID-19 infected patients include

characteristic patchy infiltration that later progresses to ground-glass capacities (158). The in vitro

antiviral potential of FAD-approved drugs, viz., All clinicians should keep themselves updated

about recent developments including global spread of the disease. 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.

ANTIVIRAL DRUGS:

Several classes of routinely used antiviral drugs, like oscltamivir (neuraminidase inhibitor),

acyclovir, ganciclovir, and ribavirin, do not have any effect on COVID-19 and, hence, are not

recommended (187). Oseltamivir, a neuraminidase inhibitor, has been explored in Chinese

hospitals for treating suspected COVID-19 cases, although proven efficacy against SARS-CoV-2

is still lacking for this drug (7). Hence, 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. It is opined that the exposure history of SARS-CoV-2 at the Wuhan seafood market

originated from human-to-human transmission rather than animal-to-human transmission (74);

however, in light of the zoonotic spillover in cOVID-19, is too early to fully endorse this idea (1).

Further genetic analysis is required.

VACCINES:
Vaccination is the most effective method for a long-term strategy for prevention and control of

COVID-19 in the future. 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. Canines

are also affected by CoVs that fall under different genera, namely, canine enteric coronavirus in

Alphacoronavirus coronavirus in Betacoronavirus, affecting the enteric and canine respiratory and

respiratory tract, respectively (129, 130). High mortality occurred especially when health-care

resources were overwhelmed. Multiple organ failure has also been reported in some COVID-19

cases 1365. Histopathological changes in patients with COVID-19 occur mainly in the lungs. 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 S1

subunit ofa corona-virus is further divided into two functional domains, an N-terminal domain and

a Cterminal domain. Structural and biochemical analyses identified a 211 amino acid region

(amino acids 319-529) at the S1 C-terminal domain of SARS-CoV-2 as the RBD, which has a key

role in virus entry and is the target of neutralizing antibodiess051 (FIG. The virus strains carried

by these two intermediate hosts were almost genetically identical to the corresponding viruses in

humans (more than 99% genome sequence identity)'.Despise an RBD that is virtually identical to

that of SARS-CoV-2, the pangolin coronaviruses known to date have no more than 92% genome

identity with SARS-CoV-2 (REF). 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 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 (121). Up to 30 March 2020, the U.S.

Later, ongoing human-to-human transmission propagated the outbreak". Most of the proteins

encoded by SARS-CoV-2 have a similar with COVID-19 showed typical features on initial CT,

including bilateral multilobar ground-glass opacities with a peripheral or posterior distribution1,

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"1, 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

retrospective studies16,120121, 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-CoV2, although some

treatments have shown some benefits in certain subpopulations of patients or for certain end points

(see later). (3d). A structural study suggested that the furin-cdeavage site can reduce the stability

of SARSCoV 2 S protein and facilitate the conformational adaption that is required for the binding

of the RBD to its receptor". These differences in the amino acid sequences might have contributed

to the difference in the pathogenic divergence of SARS-CoV-2 (16). 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. The IFR was found to be in the range of

0.3% to 0.6%, which is comparable to that of a previous Asian influenza pandemic (1957 to 1958)

(73, 277). Notably, the reanalysis of the COVID -19 pandemic curve from the initial cluster of

cases pointed to considerable human-to-human transmission. In comparison with the Guangdong

strains, pangolin coronaviruses reported from Guangxi are less similar to SARS-CoV-2, with

85.5% genome sequence identity", The repeated occurrence of SARS-CoV-2-related coronavirus

infections in pangolins from different smuggling events suggests that these animals are possible

hosts of the viruses. This property of the RBD can be utilized for designing potential SARS-CoV

RBD-containing vaccines either by using recombinant proteins or recombinant vectors that encode

RBD (175). Compared to emerging viruses like Ebola virus, avian H7N9, SARS-CoV, and MERS-

CoV, SARS-CoV2 has relatively lower pathogenicity and moderate transmissibility (15). The risk

of death among individuals infected with COVID-19 was caleulated using the infection fatality

risk (IFR). Researchers and manufacturers are conducting large-scale clinical trials to evaluate

various therapies for COVID-19. They are very closely related to SARS-CoV-2, exhibiting 92.4%

sequence similarity. Finally, COVID-19 is challenging all human beings. Common laboratory

findings include normal/low white cell counts with elevated C reactive protein (CRP). Most of

these SARS-CoV-2 nonstructural proteins have greater than 85% amino acid sequence identity

with SARS-CoV25. The phylogenetic analysis for the whole genome shows that SARS-CoV-2 is

clustered with SARS-CoV and SARS-related coronaviruses (SARSr CoVs) found in bats, placing

it in the subgenus Sarbecovirus of the genus Betacoronavirus. The receptor-binding gene region

(173, 174). On binding to epithelial cells in the respiratory tract, SARS-CoV-2 starts replicating

and migrating down to the airways and enters alveolar epithelial cells in the lungs. The comparative

analysis confirmed that the variable residues were found concentrated on the SI subunit of S

protein, an important vaccine target of the virus (150). Recent studies reported specific monoclonal

antibodies neutralizing SARS-CoV-2 infection Inhibition of virus replication. The massive

migration of Chinese during the Chinese New Year fuelled 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. It has been shown that host proteases participate in the

cdeavage of the S protein and activate the entry of SARS-CoV-2, including transmembrane

protease serine protease 2 (TMPRSS2), cathepsin L and furint"5455. Environmental samples from

the Huanan sea food market also tested positive, signifying that the virus originated from there [7].

The virus spreads faster than its twn ancestors the SARS-CoV residues for receptor binding (FIG).

However, this individual early report cannot give a solid answer to the origin of SARS-CoV-2 and

contamination, and thus a false positive result cannot be excluded. More so, future outbreaks of

viruses and pathogens of zoonotic origin are likely to continue. Therefore, apart from curbing this

outbreak. Bovine coronaviruses (BoCoVs) are known to infect several domestic and wild

ruminants (126). The first fatal case was reported on 11th Jan 2020. Several laboratories around

the world are currently developing antibody-based diagnostic tests against SARS-CoV-2 (157).

Chest CT is an ideal diagnostic tool for identifying viral pneumonia. 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 require sedatives, analgesics, and even muscle

relaxation drugs to prevent ventilator-related lung injury incoordination (122). The discovery of

diverse bat coronaviruses closely related to SARS-CoV-2 suggests that bats are possible reservoirs

of SARS-CoV-2 (RE.*"). Within this clade, SARS-CoV-2 is grouped in a distinct lineage together

with four horseshoe bat coronavirus isolates (RaTG13, RmYN02,ZC45 and ZXC21) as well as

novel coronaviruses recently identified in pangolins, which group parallel to SARS-CoV in vitro

and in vivo5- 135, Compared with convalescent plasma, which has limited availability and cannot

be amplified, monoclonal antibodies can be developed in larger quantities to meet clinical

requirements. As the epidemic progresses, commercial tests comorbidities), it may progress to

pneumonia, acute respiratory distress syndrome (ARDS) and multi organ dysfunction. The vaccine
has proved to be safe and induced considerable humoral and cellular immune response in most

recipients after a single immunization', Another vectored vaccine, ChAdOxl, and other SARSr-

CoVs (FIG). At present, nucleic acid detection techniques, like RT-PCR, are considered an

effective method for confirming the diagnosis in clinical cases of COVID-19 (148). Those variants

with this mutation make up a single subclade labelled as clade S'3,34. The most common

symptoms were fever (50%) and cough (38%). Histopathology analyses showed bilateral diffused

alveolar damage, hyaline membrane formation, desquamation of pneumocytes and fibrin deposits

in lungs of patients with severe COVID-19. This might also have contributed to the increased case

fatality rate observed in the COVID-19 outbreak.

VIEWPOINT ON SARS-CoV2 TRANSMISSION, SPREAD, AND EMERGENCE:

The novel coronavirus was identified within 1 month (28 days) of the outbreak. One case of severe

pneumonia and multi organ dysfunction in a child has also been reported [19]. 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 ). 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). The SARS-

CoV-specifie human MAb CR3022 is found to bind with SARS-CoV-2 RBD, indicating its

potential as a therapeutic agent. From experience With several outbreaks associated with known

emerging viruses, higher pathogenicity of a virus is often associated with lower transmissibility.
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. Whether the higher transmissibility of SARS-CoV-2 compared with SARS-CoV is a

gain of function associated with acquisition of the furin-like cleavage site is yet to be demonstrated.

An additional distinction is the accessory gene orf8 of SARSCoV-2, which encodes a novel protein

showing only 40% amino acid identity to ORF8 of SARS-CoV. Unlike in SARS-

CoV, this new ORF8 protein does not contain a motif that triggers intracellular stress pathways,

Notably, a SARSCoV-2 variant with a 382-nucleotide deletion covering the whole of ORF8 has

been discovered in a number of patients in Singapore, which resembles the 29- or 415-nucleotide

deletions in the ORF8 region observed in human SARS-CoV variants from the late phase of the

2002-2003 outbreak", Such ORF8 deletion may be indicative of human adaptation after cross-

species transmission from an animal host in Yunnan. In addition, seven putative ORFs encoding

accessory proteins are interspersed between the structural genes. As of 2 October 2020, -174

vaccine candidates for COVID-19 had been reported and 51 were in human clinical trials (CoVID-

19 vaccine and therapeutics tracker). Hence, they provide the possibility for the treatment and

prevention of COVID-19. However, smaller and much more numerous particles known as aerosol

particles can also be visualized, which could linger in the air for a long time and then penetrate

deep into the lungs when inhaled by someone else-, Airborne transmission was also observed in

the ferret experiments mentioned above. It is difficult to evaluate the therapeutie potential of a

drug or a combination of drugs for managing a disease based on such a limited sample size. Golden

hamsters also showed typical symptoms after being infected with SARS-CoV-2 (REF7). 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 years13608081, However, clinical manifestations differ with age.

Swine acute diarrhea syndrome coronavirus it had spread massively to all 34 provinces of China.

SARS-CoV-2 pseudovirus entry assays revealed that TMPRSS2 and cathepsin L have cumulative

effects with furin on activating virus entrys3, Analysis of the cryo-electron microscopy structure

of SARS-CoV-2 S protein revealed that its RBD is mostly in the lying-down state, whereas the

SARS-CoV S protein assumes equally standing-up and lying-down conformational states

051.5859. Since knowledge about this virus is rapidly evolving, readers are urged to update

themselves regularly.

DIAGNOSIS OF SARS-CoV-2 (COVID-19):

RNA tests can confirm the diagnosis of SARS- CoV-2 (COVID-19) cases with real-time RT-PCR

or next-generation sequencing (148, 149, 245, 246). 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 (317-319). 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. However, community

transmission might have happened before that". IBV, under Gammacoronavirus, causes diseases

of respiratory, urinary, and reproductive systems, with substantial economic losses in chickens
(131, 132). 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 [22].

DIFFERENTIAL DIAGNOSIS[21]:

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.

The sensitivity of chest CT is far superior to that of Xray screening. 4). 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 interactions remain largely unclear. Soon this lock down was of

plasma cytokines, which suggests an immunopathological process caused by a cytokine

storm"86857, In this cohort of patient, around 2.3% people died within a median time of 16 days

from disease onset 86, 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*(FIG. 36). The high genetic similarity between SARS-CoV-2 and RaTG13 supports the

hypothesis that SARSCoV-2 likely originated from bats5. In general, older men (>60 years old)

with co-morbidities are more likely to develop severe respiratory disease that requires

hospitalization differs from that in SARS-CoV in the five residues critical for ACE2 binding,

namely Y455L, L486F, N493Q. D494S and T501NS" (FIG). As some of the first reported cases

in Wuhan had no epidemiological link to the seafood market, it has been suggested that the market

may not be the initial source of human infection with SARS-CoV-2. One study from France
detected SARS-CoV-2 by PCR in a stored sample from a patient who had pneumonia at the end

of 2019, suggesting SARS-CoV-2 might have spread there much earlier than the generally known

starting time of the outbreak in France. Most patients recovered enough to be released from

hospital in 2 weeks(FIG). The result obtained from a associated with human-machine clinical study

of four patients infected with COVID-19 claimed that combination therapy using

lopinavir/itonavir, arbidol, and Shufeng Jiedu capsules (traditional Chinese medicine) was found

to be effective in managing COVID-19 pneumonia (193). Following the initial infection, human-

to-human transmission has been observed with a preliminary reproduction number (Ro) estimate

of 1.4 to 2.5 (70, 75), and recently it is estimated to be 2.24 to 3.58 (76). Hence, the possibility of

SARS-CoV-specific neutralizing antibodies providing cross-protection to COVID-19 might be

lower. Patients of older age (>60 years) and with serious pre-existing diseases have a greater risk

of developing acute respiratory distress syndrome and death-6 (FIG). Less common symptoms

include sputum production, headache, haemoptysis, diarrhoea, anorexia, sore throat, chest pain,

chills and nausea and vomiting in studies of patients in Chinal3,60,80,31, Self-reported olfactory

and taste disorders were also reported by patients in Italys. Early manifestations of COVID-19

pneumonia might not be evident in X-ray chest radiography. Genome sequencing and phylogenetic

research revealed that the COVID-19-causing coronavirus is a beta-coronavirus that belongs to the

same subtypes as SARS virus, but still exists in a variant group. Owing to these measures, the daily

number of new cases in China started to decrease steadily", However, despite the declining trend

in China, the international spread of COVID-19 accelerated from late February. Such an S1-$2

cleavage site is not observed in all related viruses belonging to the subgenus Sarbecovirus, except

for a similar three amino acid insertion (PAA) in RmYN02, a bat derived coronavirus newly

reported from Rhinolophus malayanus in China (FIG). 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. 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, article

gives a bird's eye view about this new virus. Although the insertion in RmYN02 does not

functionally represent a polybasic cleavage site, it provides support for the notion that this

characteristic, initially considered unique to SARS-COV-2, has been acquired naturally2".

Immunohistochemistry assays detected SARS-CoV-2 antigen in the upper airway, bronchiolar

epithelium and submucosal gland epithelium, as well as in type I and type II pneumocytes, alveolar

macrophages and hyaline membranes in the lungs. Animal models used for studying SARS-CoV-

2 infection pathogenesis include non-human primates rhesus macaques, cynomolgus monkeys,

marmosets and African green monkeys, mice wild-type mice with mouse-adapted virus and human

ACE2-transgenic or human ACE2-knock- in mice), ferrets and golden hamsters.ab7, In non-

human primate animal models, most species display clinical features similar to those of patients

with COVID-19, including virus shedding, virus replication and host responses to SARS-CoV-2

infection, For example, in the rhesus macaque model, high viral loads were detected in the upper

and 216 countries and regions from all six continents had reported more than 20 million cases of

COVID-19, and more than 733,000 patients had died. Exudative inflammation was also shown in

some cases. The number of confirmed cases suddenly increased, with thousands of new cases

diagnosed daily during late January'". Interferons induce the expression of diverse interferon-

stimulated genes, which can interfere with every step of virus replication. SARS-CoV-2-infected

ferrets shed of persistent local transmission or contact with patients with similar travel history or

those with confirmed COVID-19 infection. The chest CT imaging abnormalities associated with

COVID-19 pneumonia have also been observed even in asymptomatic patients.

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. Such a situation poses a disease

outbreaks. Significant threat to travelers, since people from different countries are on board, which

favors the introduction of the pathogen (320). Time alone will tell how the virus will impact our

lives here in India (2). Another related coronavirus has been reported more recently in a

Rhinolophus malayanus bat sampled in Yiunnan Thic novel hat virnc denoted 'RmYN02 system

(30). Similarly the neonatal cases that have been reported have been mild [20].

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 considerable protection in mice against a MERS-CoV lethal

challenge. Interstitial pneumonia and inflammatory responses were found in both young and aged

mice after infection with the mouse-adapted strain. To control CoVID19, China implemented

unprecedentedly strict public health measures. The RBD of the S1 subunit of S protein has a

superior capacity to induce neutralizing antibodies. The rapid replication of SARS-CoV-2 in the

lungs may trigger a strong immune response. It is also abnormal in asymptomatic patients/ patients

with no clinical evidence of lower respiratory tract involvement. 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 settings, such as migrant worker communities, slaughter-

houses and meat packing plants, indicating the necessity of isolating infected people. Nosocomial
transmission was not the main source of transmission in China because of the implementation of

infection control measures in clinical settings. Single-cell RNA sequencing data showed that

TMPRSS2 is highly expressed in several tissues and body sites and is co-expressed with ACE2 in

nasal epithelial cells, lungs and bronchial branches, which explains some of the tissue tropism of

SARS-CoV-2(REFSS63). It is also the first approved option by the European Union for treatment

of adults and adolescents with pneumonia requiring supplemental oxygen. Several international

phase IlI 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. 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) (200). 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

assessed clinically. Biotechnology company Regeneron is attempting to recognize potent and

specific MAbs to combat COVID-19. 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

symptoms8, 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

(REFS7-7). The first such instance was in 2002-2003 when a or even die, whereas most young

people and children have only mild diseases (non pneumonia or mild pneumonia) or are

asymptomatic"81.3, Notably, the risk of disease was not higher for pregnant women. However

cases may be asymptomatic or even without fever. Notably, the RBD of Guangdong pangolin

coronaviruses is highly similar to that of SARS-CoV-2. Preliminary findings have suggested

improved clinical status after the treatment 5,154, The FDA has provided guidance for the use of

COVID-19 convalescent plasma under an emergency investigational new drug application.

According to the National Health Commission of China, the total number of cases continued to

rise sharply in early February at an average rate of more than 3,000 newly confirmed cases per

day. 2). 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 (4). 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). Feline enteric and feline infectious peritonitis (FIP) viruses are the two major

feline CoVs (128), where feline CoVs can affect the gastrointestinal tract, abdominal cavity

(peritonitis), respiratory tract, and central nervous system (128). A randomizod double-blinded

phase II trial of an adenovirus type vectored vaccine expressing the SARS-CoV-2 S protein,

developed by CanSino Biologicals and the Academy of Military Medical Sciences of China, was

conducted in 603 adult volunteers in Wuhan. For example, a cohort study in London revea 44%

of the frontline health-care workers from a hosp were infected with SARS-CoV-2 (REF*). The

high transmissibility of SARS-CoV-2 may be attributed to the unique virological features of

SARS-CoV-2. Efforts should be made to transmission risk (228). Owing to these residue changes,
interaction of SARS-CoV-2 with its receptor stabilizes the two virus-binding hotspots on the

surface of hACE2 REFS) (FIG. The RBM mediates con tact with the ACE2 receptor (amino acids

437-507 of SARSCoV-2 S protein), and this region in SARS-CoV-2 differs from that in SARS-

CoV in the five residues critical. The interferon response is one of the major innate immunity

defences against virus invasion. No severe or critical cases were seen. 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. It is generally accepted that

SARS-CoV-2 is more transmissible than SARS-CoV and MERS-CoV; however, determination

of an accurate reproduction number (R0) for COVID-19 is not possible yet, as many asymptomatic

infections cannot be accurately accounted for at this stage". Phylogenetic analysis confirms that

SARS-CoV-2 closely clusters with RaTG13 (FIG. This novel bat virus, denoted "RmYNO2, is

93.396 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). Transmission to healthcare

workers caring for patients was described on 20th Jan, 2020. Several companies across the world

are currently focusing on developing and marketing SARS-CoV-2-specific nucleic acid detection

kits. Multiple laboratories are also developing their own in-house RT-PCR. One of them is the

SARS-CoV-2 nucleic acid detection kit produced by Shuoshi Biotechnology (double fluorescence

PCR method) (150). Large clusters of infection have been reported from an increasing number of

countries The high transmission efficiency of SARS-CoV-2 and the abundance of international

travel enabled rapid worldwide spread of COVID-19. The COVID-19 outbreak has also been

associated with severe economic impacts globally due to the sudden interruption of global trade

and supply chains that forced multinational companies to make decisions that led to significant

economic losses (66). On 11 March 2020, the WHO officially characterized the global COVID-
19 out break as a pandemic". Another serological study detected SARS-CoV-2 neutralizing

antibodies in cat serum samples collected in Wuhan after the COVID-19 outbreak, providing

evidence for SARS-CoV-2 infection in cat populations in Wuhan, although the potential of

SARSCoV-2 transmission from cats to humans is currently uncertain.

RECEPTOR USE AND PATHOGENESIS

SARS-CoV-2 uses the same receptor as SARS-CoV, angiotensin-converting enzyme 2 (ACE2) -

", Besides human ACE2 (hACE2), SARS-CoV-2 also recognizes ACE2 from pig, ferret, rhesus

monkey, civet, cat, pangolin, rabbit and dog (434.59), The broad receptor usage of SARS-CoV-2

implies that it may have a wide host range, and the varied efficiency ofACE2 usage in different

animals may indicate their different susceptibilities to SARS-CoV-2 infection. BoCoV-like viruses

have been noted in humans, suggesting its zoonotic potential as well (127). Many of these vaccine

candidates are in phase II testing, and some have already advanced to phase III trials. However,

this treatment may have adverse effects by causing antibody-mediated enhancement of infection,

transfusion-associated acute lung injury and allergic transfusion reactions.

Monoclonal antibody therapy is an effective immuno-therapy for the treatment of some viral

infections in select patients. However, the high cost and limited capacity of manufacturing, as well

as the problem of bioavailability, may restrict the wide application of monoclonal antibody

therapy.
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 neighbors. 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. In such

situations, a chest CT examination can be performed, as it is considered highly specific for

COVID-19 pneumonia (118). Those patients having COVID-19 pneumonia will exhibit the typical

ground-glass opacity in their chest CT images (154). 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.

Previous studies identified type I interferons as a promising therapeutic candidate for SARS" In

vitro data showed SARS-CoV-2 is even more sensitive to type I interferons than SARS-CoV,

suggesting the potential effectiveness of type I interferons in the early treatment of COVID-19

(REF 5). This is impressively fast compared to the time taken to identify SARS- CoV reported in

Foshan, Guangdong Province, China (125 days) (68). 36,c). These abnormalities suggest that

pangolins are unlikely to be the reservoir of these coronaviruses but more likely acquired the

viruses after spillover from the natural hosts.

An intermediate host usually plays an important role in the outbreak of bat-derived emerging

coronaviruses; for example, palm civets for SARS-CoV and dromedary camels for MERS-CoV.
 BUSINESS LETTER FORMAT

Company, Inc.

123 Alphabet Drive

Los Angeles, Calidormia 90002

15 October 2016
Mr. John Doe

Customer Service Representative

Widgets Galore, Inc.

987 wWidget Street

Mami, Florida 33111

Dear Mr.Doe:

I am writing you concerning a recent purchase of widgets. Approximately two weeks ago, on

October 1, I ordered a total of 50 widgets for Company, Inc via the Widgets Galore client

webpage. I received an email notitfication two days later confirming the receipt of payment and

the shipment of the widgets. According to your website, shipments should reach their destination

within 3-5 business days of being sent, but I have yet to receive the widgets. Do you have any

information on what may have happened to delay the shipment or where the shipment is

currently?

I have worked with Widgets Galore, Inc. in the past and have the greatest confidence in your

products and customer service. We need the shipment of widgets soon, however, and I hoped you

might be able to provide me with an idea of when I can expect them. Thank you in advance for

any help you might be able to offer.

Sincerely,

Sam Brown

Vice President of Company, Inc.

55-555-555

sbrown@comparyinc.com

BUSSINESS LETTER MATCHING

1.Date A) 100 Broadway Lane, New Parkland, CA, 91010

Cell: (555) 987-1234 example-

email@example.com

2. Body: detail

B) March 16, 2018

3. Salutation

C) R.Roland

ABC industries

123 Warehouse Lane

New Parkland, CA 91010

4. Signature

D) Dear Mr. Raland,

5. Your address

E) Flease accept my letter of

resignation from my warehouse associate position

with ABC

Industries. My final day an the job will be

April 28th, 2015. I will be moving on to a

warehouse supervisor position with another

firm in order to advance in my career.

6. Body: Main ldea

F) I truly have had a positive

experience in my time here at ABC. The work environment

is extremely positive, and I can always count on my co-

workers for support. Thank you so much for the chance to

gain information about the manufacturing industry

and warehouse efficiency. 7. Recipient's address

8. Closing G)I want you to be assured that i will continue to give 100% on the job from now until

my last day
 Feel free to let me know how I can make the

transition process a smooth one. I’m happy to

help in any way I can. You can reach me at

9. Body: Restate main idea; call to action (555) 987-1234 if you need anything

further.

H) Sincerely.

I) Jerome Watson
[Sender's Name]

[Sender's Company Name]

[Sender's Street Address]

[Sender's City, State/Province, & Zip/Postal Code]

[Sender's phone number and or email address]

[Date]

[Recipient's Name]
[Recipient's Company Name]

[Recipient's Street Address]

[Recipient's City, State/Province, & Zip/Postal Code]

[Recipient's phone number and or email address]

[Subject]

[Dear Name],

[Introduction-this is where you explain the purpose of the letter, why you are writing it, what you

hope to achieve from, and any other important information you want to get out upfront.]

[Middle Section-this is where you elaborate and provide more detail about what you outlined in

the first paragraph. There may be several more paragraphs like this depending on how long the

letter needs to be]

[Conclusion-this is the place where you wrap up and summarize things. There may be a call to

action or next steps included in this paragraph]

[Sincerely],

[Signature]
[Name of Sender]

COMPANY NAME

Recipient Name

Street Address

City, ST ZIP Code

Date

Dear Recipient Name,

To get started right away, just select any placeholder text (such as this) and start typing to replace

it with your own. Select the contact information in the footer to add your contact information.

Think a document that looks this good has to be difficult to format? Think again! To easily apply

any text formatting you see in this document, on the Home tab of the ribbon, check out Styles.

Sincerely,
Your Name

Street Address PHONE Enter Phone

YOUR LOGO HERE
Address 2, FAX Enter Fax

City, ST, ZIP CODE EMAIL Enter EMAIL

County

WEBSITE Enter Website

FORMAL BUSINESS LETTER

[{Address Sender}]
Date: June 30, 2021

[{Name Recipient}]

[{Address Recipient}]

Subject: [{subject}]

Dear Mr/Mrs [{Name}],

Working with you, company for the past two years has been an excellent experience.

Unfortunately, we have to inform you that our Company has no longer in need of your services.

This is because our management has decided to move our marketing strategies in the different

direction and consequently to involve new partners in our business. Since the consulting services

you have provided for our company are not complementary with current marketing strategy, we

have to cancel our contract with you.

We take this opportunity to thank you for the wonderful work you have done for us so far.

Nevertheless, we hold high hopes to remain on good terms with you and your company, and if we

require services similar to what you have provided for us in the past, we would certainly like to

consider you again.

Your sincerely,

[{Signature}]

[{Formal Name}] [{Title}]

[{Organization}]

CONGRATULATION ON YOUR SUCCESS

33. Fifth Avenue,

4th cross road

Mumbai -89

Maharashtra

Date: 18th June 2020

Dear Preeti
How are you? How are your family members? How is the weather there? Hope you are doing well.

l am also fine here.

I heard the news of you holding 1st rank in the class. I feel really happy and proud of you.I would

like to congratulate you for the same. I know you must have done a lot of hardwork for it and

finally you have achieved what you wanted.

I am hoping that you achieve all the success in future. Keep it up. Also, will try to meet you in

person and congratulate you. If we meet ever will surely celebrate for your success. Till then take

care of yourself and your family.

Take care.

With Love.

Pooja

Business Letter Format

 Company Letterhead

Company Name

610 Fountain Ave

Burlington, NI 08016

Today's Date

Burlington Township Student

Street Address

City, State Zip

Dear Student,

Use this sample letter as a template to help you complete your activities throughout this course. I

have purposely set up the spacing and content to make it easier for you to delete existing test and

replace it with the content that you need to use. Please be sure to use all the taoh provided to you

so that you are more efficient with your work.

Be sure to copy down the text boxes I have provided, they may be helpful when you need to

compose different types of business letters. Be sure to save ths decument as: Letter Template

Sincerely,

Mr. Carsen

Business Ed Teacher

Enclosure

Urs,

Company Name

Date

Street Address

City.ST ZIP Code

Dear Recipient,
To get started right away, just tap any placeholder text (such as this) and start typing to replace it

with your own.

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tab of the ribbon, just tap the option you need.

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add automatic page numbering.

Sincerely,

Yout Name.
STREET ADDRESS, CITY, ST, ZIPCODE

T (123)456-7890, WWW.COMPANY.COM

BUSINESS LETTER SAMPLE FORMAT

Company Name

#Street

City. State, Zip Code

Phone and Fax numbers

Date

Embassy of

Attention: Visa Department

Dear Sirs,

This letter is to introduce (Applicant's name), who is our (state exact detailed position) with

(Company Name). His/her job duties consist of the following: (state exact job duties in detail).

(Applicants name) wishes to visit your country from (Proposed Date of entry) to (Propose Date

of Exit) in order to (Exact purpose of trip in Detail).

We are requesting a Business visa to be issued. While in ( name of country ), he/she will be

contacting

Contact person's name

Company Name

Company Street address and Phone Number

(Company Name) hereby guarantees the expenses of (applicant's name) trip including return

airfare to the United States.

Sincerely,

Authorized signer other than the Applicant

(Title)

Business Letter Format

Company Letterhead

Company Name
610 Fountain Ave

Burlington, NJ 08016

Today's Date

Burlington Township Student

Street Address

City, State Zip

Dear Student:

Use this sample letter as a template to help you complete your activities throughout this course. I

have purposely set up the spacing and content to make it easier for you to delete existing text and

replace it with the content that you need to use. Please be sure to use all the tools provided to you

so that you are more efficient with your work.

Be sure to copy down the text boxes I have provided, they may be helpful when you need to

compose different types of business letters. Be sure to save this document as:

Letter Template.

Sincerely,

Mr. Carson
Business Ed.

Teacher Enclosure

urs

129, Navyug Apartments

Pitampura, Delhi-110034

March 01, 2019

Dear Rudra

It's been a while since I've heard from you. Where have you been? I hope this letter finds you in

the best of your health.

As summers are approaching, I was thinking if we could spend the summer break together at my

place in Mumbai. I will introduce you to all my friends and close relatives. I will give you a city

tour as well. We will spend some quality time in the afternoons near the sea shore. To add cherry

on the cake, the weather here is very pleasant during those days due to sea winds.
I am excited even at the thought of you and I spending the summer together after so long. I have

to tell you a lot of things and expect the same from you. Give my regards to aunty and uncle!

Hope to see you soon.

Yours lovingly

Sakshi/Saksham

Essay Plan

• Paragraph 1:
 Introduce The Topic.

• Paragraph 2:

Give points of view and information, in support of argument with reasons.

• Paragraph 3:

Give contrasting views.

• Paragraph 4:

Conclude.

(Give your own opinion of interpretation of the facts)

EASY ENGLISH 444.

 ESSAY WRITING

• Planning and Writing an Essay:

Read the question or the essay title carefully to make sure you understand exactly

what is required.

• Brainstorming:

Quickly note down some ideas on the topic as you think of them. Write down some

vocabulary that you know you will need to write about this subject.

• Planning:

If you are asked to discuss a topic or give your opinion, it is important to organize

your thoughts and present your arguments clearly in paragraphs, and to work out

the structure of your essay before you start to write.

 EASY ENGLISH 444.

Essay Example

Education means considerably more than just teaching a student to read, write, and manipulate

numbers Computers, the Internet, and advanced electronic devices are beccoming essential in
everyday life and have changed the way information is gathered. How this new technology is

utilized in the curiculum and managed by teachers will have an important role to play in widening

the resource and knowledge base for all students.

Technology affects the way teachers teach and students learn. To make the best use of information

technology (IT), schools need a workable plan on fully integrate it into all aspects of the

curriculums students are taught how, why, and when to use technology to further enhance their

learning.

If a school does not havea clear plan of how and why it wishes to implement IT, then it runs the

risk of wasting money. In schools today. nearly all classrooms have access to a computer.

However, many schools mistake this as incorporating information technology into the curriculum.

School staff need to research what IT is available and what would best serve the school's purpose.

Not simply purchase the latest equipment. There should be a policy stating how IT is going to

assist pupils' development and what teachers want pupils to achieve (Reksten, 2000). Staff

members need to be clear about what they want IT to do for them before they can start

incorporating it into their lessons.

The only way information technology is going to be useful to schools is if all staff members are

well-informed and fully supported. It is the principal’s responsibility and should be part of the

school's plan, to ensure that all staff are consulted about the changes, and that the change is
carefully organised. Some teachers may be resistant, especially if they have not had much

experience with computers, so training teachers is essential in implementing IT into the school

curriculum. Staff members must feel involved in the process of acquiring technology, and in

learning how to operate it, in order for them to increase their confidence in using IT as a curriculum

tool. Teachers are only going to be able to incorporate IT into their lessons if they are competent

users themselves (Reksten, 2000).

In addition, teachers need to be aware that IT within the classroom is extremely flexible, but that

they need to plan what purpose IT serves in each lesson. The skills a child learns are the important

part of any lesson, and it is the same with technology. IT needs to be used and understood in all

subjects in the same way as the ability to read is necessary for all subjects, and "must be used

across the curriculum, in the same way that a pen and pencil used in most subject areas” (Ager

2000, p. 15). The best way to plan the use of IT in the classroom is to approach it as simply a

learning tool that is more advanced (and more exciting) than the traditional pen and paper.

It is vitally important for students to be taught the strategies for using IT. Children also need to be

fully informed about the capabilities of IT before being asked to use it, Pupils should be aware that

the contexts in which they use it will change, and they need to know what the appropriate use of

IT is and what is not. Whilst it is important that children learn to use IT effectively, teachers must

emphasize that IT is not always suitable. According to Apter (1968), the danger is that the

"computer dehumanizes people and inevitably leads them to act like machines themselves" (p.581)