Covid-19

Introduction

Over the past 2 decades, coronaviruses (CoVVs) have 

been associated with significant disease

Outbreaks in East Asia and the Middle East. Th

Severe acute respiratory syndrome (SARS) and the

Middle East respiratory syndrome (MERS) began to 

emerge in 2002 and 2012, respectively. Recently, a

Novel coronavirus, severe

Acute respiratory

Syndrome coronavirus 2 (SARS-CoV-2), causing 

coronavirus disease 2019 (COVID-19), emerged in

Late 2019, and it has posed a global health threat,

Causing an ongoing pandemic in many countries and

Territories (1).

Health workers worldwide are currently making 

efforts to control further disease outbreaks caused 

by the novel CoV (originally named 2019-nCoV), 

which was first identified in Wuhan City, Hubei 

Province, China, on 12 December 2019. On 11February 2020, the World Health Organization

(WHO) announced the official designation for the

Current CoV-associated disease to be COVID-19,

Caused by SARS-CoV-2. The primary cluster of 

patients was found to be connected with the 

Huanan South China Seafood Market in Wuhan (2). 

CoVs

Belong to the family Coronaviridae (subfamily

Coronavirinae), the members of which infect a broad

trimerieSI locates itself on top of the trimeric S2 stalk 

(45). Recently, structural analyses of the S

proteins of COVID-19 have revealed 27 amino acid

substitutions within a 1,273-amino-acid stretch (16).

Six substitutions are located in the RBD (amino

Acids 357 to 528), while four substitutions are in the

RBM at the CTD of the S1 domain (16). Of note, no

Amino acid change is seen in the RBM, which binds

Directly to the angiotensin-converting enzyme-2

(ACE2) receptor in SARS-CoV (16, 46). At present,

The main emphasis is knowing how many 

differencesWould be required to change the host tropism. 

Sequence comparison revealed 17 nonsynonymous 

changes between the early sequence of SARS-CoV-2

And the later isolates of SARS-CoV. The changes

Were found scattered over the genome of the virus,

With nine substitutions in ORFlab, ORF8 (4 

substitutions), the spike gene (3 substitutions), and

ORF7a (single substitution) (4). Notably, the same 

nonsynonymous changes were found in a familial 

cluster, indicating that the viral evolution happened

During person-to-person transmission (4, 47). Such 

adaptive evolution events are frequent and 

constitute

A constantly ongoing process once the virus spreads

Among new hosts (47). Even though no functional 

changes occur in the virus associated with this

Adaptive evolution, close monitoring of the viral

Absence of this protein is related to the altered

Virulence of coronaviruses due to changes inMorphology and tropism (54). The E protein consists 

of three domains, namely, a short hydrophilic amino 

terminal, a large hydrophobic transmembrane

Domain, and an efficient C-terminal domain (51).

The SARS-CoV-2 E protein reveals a similar amino

Acid constitution without any substitution (16).

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 

(55, 56). It contains three highly conserved and

Distinct domains, namely, an NTD, an RNA-binding

Domain or a linker region (LKR), and a CTD (57).

The NTD binds with the 3’ end of the viral genome,Perhaps via electrostatic interactions, and is highly 

diverged both in length and sequence (58). The

Charged LKR is serine and arginine rich and is also

Known as the SR (serine and arginine) domain (59). 

The LKR is capable of direct interaction with in vitro

RNA interaction and is responsible for cell signaling 

(60, 61). It also modulates the antiviral response of 

the host by working as an antagonist for interferon

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) (16). All

These proteins play a specific role in viral replication(27). Unlike the accessory proteins of SARS-CoV,

SARS-CoV-2 does not contain 8a protein and has a

Longer 8b and shorter 3b protein (16). 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 (16).

The virus structure of SARS-CoV-2 is depicted inSpike glycoprotein (S) (required for the entry of the 

infectious virion particle)

Membrane protein (M) (most abundant viral 

protein)Major structural proteins

Envelope glycoprotein (E) (smallest among the major 

structural proteins)Nucleocapsid protein (N) +single-stranded positive 

sense RNA genome

Lipid bilayer

FIG 2 SARS-CoV-2 virus structure.

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 (Fig. 4). As of 13 May 2020,

SARS-CoV-2 confirmed cases have been reported in 

more than 210 countries apart from China (Fig. 3 and 

4) (WHO Situation Report 114) (25, 64). 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

Of cases, 1,322,054, and 79,634 deaths.Number

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

COVID-19 has also been contirmed on a cruise

Ship, named Diamond Princess, quarantined in

Japanese waters (Port of Yokohama), as well as on

Other cruise ships around the world (239) (Fig. 3).

The significant events of the SARS-CoV-2/COVID-19 virus outbreak occurring since 8 December 2019 

are presented as a timeline in Fig. 5.

Major events of current coronavirus COVID-19 

disease outbreak

03 Feb 2020 Fint complete genomefrom apart 1Feb, 

2020 37 pas e anCW quarantined by the Japanese 

Ministiy ofHewth ontximond

8Jan 2020

Sjan 2 wuhan heath committee ecude SARS and 

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Edarnosnces a

wHO naes the Ohease C0VID-19 u wii named 

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31 Dec, 2019

24 Jan 2020

Fiest competo

Oluted am Wuhar

Wuhan notes 27

Prneumonia cases Dole cue ot pneumonia 

Pheumonia patient 9enome trom UA u D

19 Jan, 200 Fest cell aulture isolation Fest genome 

relased by WH0 declanes t a Public Fudan Uiveruty 

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02 Feb. 2020Dec, 2019

7 Jan, 2020

30 Jan. 2020

1 Jan, 20 China ckoses Wuhan

It death roported outside of Chra, n Philippines

Smpom onset of the 41 confmed 2019-eCocases

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05 Ape 2020 he United States National Total 

confmed eterinary Servoes

13 May. 2020

27 Mar, 202006 Mat. 2020 3S33 people dincluding 21 positie on 

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14Feb, 20 Second death outside China Princess 

crulise ship no travel history to China

Betgium health posible transmission of COVID-19to 

domestik catthe caast of Califormia (US

20 Feb. 20

4120424 with

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287 399 deaths worldwide

Brorw 200 h New York.

16 Feb 0 ed

28 Feb, 20220

13 Feb, 2020

Mac 2020Ap, 2020

Ap, 2020

D the

Ases e he o with

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45526 deaths worlkawide

Of coviD-19 to pet dogs

NO Pet cats

FIG 5 Timeline depicting the significant events that 

occurred during the SARS-CoV-2/COVID-19 virus 

outbreak. The timeline describes the significant 

events during the current SARS-CoV-2 outbreak, 

from 8 December 2019 to 13 May 2020.

At the beginning, China experienced the majority of 

the burden associated with COVID-19 in the form of 

disease morbidity and mortality (65), but overTime the COVID-19 menace moved to Europe, 

particularly Italy and Spain, and now the United

States has the highest number of confirmed cases

Another study, the average reproductive number of

COVID-19 was found to be 3.28, which is

Significantly higher than the initial WH0 estimate of 

14 to 2.5 (77). 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 presentIn the live-animal market were identified to be the

Intermediate hosts of the SARS outbreak in China

(78). Several wildlife species were found to harbor 

potentially evolving coronavirus strains that can

Overcome the species barrier (79). One of the main

Principles of Chinese food culture is that live- 

slaughtered animals are considered more nutritious

5).

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

As an entry receptor while exhibiting an RBD similar

To that of SARS-CoV (17, 87, 254, 255). Several

Countries have provided recommendations to their 

people traveling to China (88, 89). Compared to the 

previous coronavirus outbreaks caused by SARS-

CoV and MERS-CoV, the efficiency of SARS-CoV-

2 human-to-human transmission was thought to be

Less. This assumption was based on the finding that

Health workers were affected less than they were in

Previous outbreaks of fatal coronaviruses (2).

Superspreading events are considered the mainCulprit for the extensive transmission of SARS and

MERS (90, 91). Almost half of the MERS-CoV

Cases reported in Saudi Arabia are of secondary

Origin that occurred through contact with infected

Asymptomatic or symptomatic individuals through

Human-to-human transmission (92). The occurrence

Of superspreading events in the COVID-19 outbreak

Cannot be ruled out until its possibility is evaluated.

Like SARS and MERS, COVID-19 can also infect

The lower respiratory tract, with milder symptoms

(27). The basic reproduction number of COVID-19 

has been found to be in the range of 2.8 to 3.3 based 

on real-time reports and 3.2 to 3.9 based on 

predicted

Infected cases (84).Route warrants the introduction of negative fecal 

viral

Nucleic acid test results as one of the additional

Discharge criteria in laboratory-confirmed cases of 

COVID-19 (326).

The COVID-19 pandemic does not have any

Novel factors, other than the genetically unique

Pathogen and a further possible reservoir. The cause

And the likely future outcome are just repetitions of

Our previous interactions with fatal coronaviruses. 

The only difference is the time of occurrence and the

Genetic distinctness of the pathogen involved.

Mutations on the RBD of CoVs facilitated theirCapability of infecting newer hosts, thereby 

expanding their reach to all corners of the world

(85). This is a potential threat to the health of both

Animals and humans. Advanced studies using 

Bayesian phylogeographic reconstruction identified 

the most probable origin of SARS-CoV-2 as the bat

SARS-like

Circulating

The

In

coronaVirus,

Rhinolophus bat family (86). Phylogenetic analysis of 

10 whole-genome sequences of SARS-CoV-2 showed 

that they are related to two CoVs of bat origin, 

namely, bat-SL-

CoVZC45 and bat-SL-CoVZXC21, which wereReported during 2018 in China (17). It was reported

That SARS-CoV-2 had been confirmed to use ACE2

As an entry receptor while exhibiting an RBD similar

Tever, cough, and sputum (83). Hence, the clinicians

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 (84). Increasing 

reports of SARS-CoV-2 in sewage and

Warrants the need forWastewater

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 (328). 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 theStool, 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 (327). The calculated viral RNA copy numbers

Determine the number of infected individuals. The

Suffering from novel SARS-CoV-2, with more than

4,170,424 cases and 287,399 deaths across the 

globe.

There is an urgent need for a rational internationalCampaign against the unhealthy food practices of 

China to encourage the sellers to increase hygienic

Food practices or close the crude live-dead animal 

wet markets. There is a need to modify food policies

At national and international levels to avoid further

Life threats and economic consequences from any

Emerging or reemerging pandemic due to close

Animal-human interaction (285).

Even though individuals of all ages and sexes are 

susceptible to COVID-19, older people with an

Underlying chronic disease are more likely to

Become severely infected (80). Recently, individuals

With asymptomatic infection were also found to act 

as a source of infection to susceptible individuals

(81). Both the asymptomatic and symptomaticPatients secrete similar viral loads, which indicates

That the transmission capacity of asymptomatic or

Minimally symptomatic patients is very high. Thus,

SARS-CoV-2 transmission can happen early in the 

course of infection (82). Atypical clinical 

manifestations have also been reported in COVID-19 

in which the only reporting symptom was fatigue.

Such patients may lack respiratory signs, such as 

fever, cough, and sputum (83). Hence, the clinicians

Turtles, ducks, fish, Siamese crocodiles, and other

Animal meats without any fear of COVID-19. The

Chinese government is encouraging people to feel

They can return to normalcy. However, this could be

A risk, as it has been mentioned in advisories thatPeople should avoid contact with live-dead animals

As much as possible, as SARS-CoV-2 has shown

Zoonotic spillover. Additionally, we cannot rule out

The possibility of new mutations in the same virus

Being closely related to contact with both animals

And humans at the market (284). In January 2020,

China imposed a temporary ban on the sale of live-

Dead animals in wet markets. However, now

Hundreds of such wet markets have been reopened 

without optimizing standard food safety and

Sanitation practices (286).

With China being the most populated country in

The world and due to its domestic and internationalFood exportation policies, the whole world is now 

facing the menace of COVID-19, including China

Itself. Wet markets of live-dead animals do not

Maintain strict food hygienic practices. Fresh blood

Splashes are present everywhere, on the floor and

Tabletops, and such food customs could encourage

Many pathogens to adapt, mutate, and jump the

Species barrier. As a result, the whole world is 

suffering from novel SARS-CoV-2, with more than

From experience With several outbreaks

Associated with known emerging viruses, higher

Pathogenicity of a virus is often associated with 

lower transmissibility. Compared to emergingViruses 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 calculated using the infection fatality 

risk (IFR). 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

Considerable

Human-to-human

Pointed

ToTransmission. 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). 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). In

Another study, the average reproductive number ofPossible orign o1 SARS-CoV-2 and the luSt mode o 

disease transmission are not yet identified (70).

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 (Fig. 6). The restaurants of this market are 

well-known for providing different types of wild 

animals for human consumption (71). The Huanan

South China Seafood Market also sells live animals,

Such as poultry, bats, snakes, and marmots (72). This 

might be the point where zoonotic (animal-to- 

human) transmission occurred (71). Although

SARS-CoV-2 is alleged to have originated from an 

animal host (zoonotic origin) with further human-to- 

human transmission (Fig. 6), the

Likelihood of

Foodborne transmission should be ruled out withFurther investigations, since it is a latent possibility 

(1). 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 (Fig. 6). Still, whether 

blood transfusion and organ transplantation (276), 

as well

As transplacental and perinatal routes, are possible

Routes for SARS-CoV-2 transmission needs to be

Determined (Fig. 6).

Responsible for MERS-CoV and SARS-CoV (3). The 

newly emerged SARS-CoV-2 isa group 2B

Coronavirus (2). The genome sequences of SARS-Of As of 13 May 2020, a total of 4,170,424

CoV-2 obtained from patients share 79.5% sequence

Similarity to the sequence of SARS-CoV (63).

Confirmed cases of COVID-19 (with 287,399 deaths)

Have been reported in more than 210 affected 

countries worldwide (WHO Situation Report 114

And deaths. 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). The recent increase in the number ofConfirmed 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). This might also 

have contributed to the increased case fatality rate

Observed in the COVID-19 outbreak.

Viewpoint on SARS-CoV-2 Transmission,

Spread, and Emergence

The novel coronavirus was identified within 1

Month (28 days) of the outbreak. This is impressively

Fast compared to the time taken to identify SARS- 

CoV reported in Foshan, Guangdong Province, China 

(125 days) (68). Immediately after the confirmation 

of viral etiology, the Chinese

Virologists rapidly released the genomic sequence ofSARS-CoV-2, which played a crucial role in 

controlling the spread of this newly emerged novel 

coronavirus to other parts of the world (69). The 

possible origin of SARS-CoV-2 and the first mode of

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 (Fig. 1). 

The CoVs from the subgenus Sarbecovirus appeared 

jointly in SplitsTree and divided into three 

subclusters, namely, SARS-CoV-2, bat-SARS-like- CoV 

(bat-SL-CoV), and SARS-CoV (Fig. 1). In the case of 

other subgenera, like Merbecovirus, all of the 

sequences grouped in a single cluster, whereas inEmbecovirus, 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

We assessed the nucleotide percent similarityUsing the MegAlign software program, where the 

similarity between the novel SARS-CoV-2 isolates

Was in the range of 99.4% to 100%. Among the 

other

Serbecovirus CoV sequences, the novel SARS-CoV-

2 sequences revealed the highest similarity to bat-

SL-CoV, with nucleotide percent identity ranges

Between 88.12 and 89.65%. Meanwhile, earlier

Reported SARS-CoVs showed 70.6 to 74.9% similarity 

to SARS-CoV-2 at the nucleotide level.

Further, the nucleotide percent similarity was 55.4%,

45.5% to 47.9%, 46.2% to 46.6%, and 45.0% to 46.3% 

to the other four subgenera, namely, Merbecovirus, 

and

Hibecovirus,Nobecovirus,

Embecovirus, respectively. The percent similarity

Index of current outbreak isolates indicates a close

Relationship between SARS-CoV-2 isolates and bat-

SL-CoV, indicating a common origin. However,

Particular pieces of evidence based on further

Complete genomic analysis of current isolates are

Necessary to draw any conclusions, although it was

Ascertained that the current novel SARS-CoV-2

Isolates belong to the subgenus Sarbecovirus in the

Diverse range of betacoronaviruses. Their possible

Ancestor was hypothesized to be from bat CoV 

strains, wherein bats might have played a crucial role 

in harboring this class of viruses.N Protein

The N protein of coronavirus is multipurpose.

Among several functions, it plays a role in complex

Formationwith the viral genome, facilitates M

Protein interaction needed during virion assembly,

And enhances the transcription efficiency of the 

virus

(55, 56). It contains three highly conserved and

Distinct domains, namely, an NTD, an RNA-binding 

domain or a linker region (LKR), and a CTD (57).

The NTD binds with the 3’ end of the viral genome,

Perhaps via electrostatic interactions, and is highlyDiverged both in length and sequence (58). The 

charged LKR is serine and arginine rich and is also 

known as the SR (serine and arginine) domain (59). 

The LKR is capable of direct interaction with in vitro 

RNA interaction and is responsible for cell signaling 

(60, 61). It also modulates the antiviral response of 

the host by working as an antagonist for interferon 

(IFN) and RNA interference (62). 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

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 (48). It binds to the

Nucleocapsid and acts as a central organizer of

Coronavirus assembly (49). Coronavirus M proteins

Are highly diverse in amino acid contents but 

maintain overall structural similarity within different 

genera (50). The M protein has three 

transmembrane domains, flanked by a short amino 

terminus outside the virion and a long carboxy 

terminus inside the

Virion (50). Overall, the viral scaffold is maintained

By M-M interaction. Of note, the M protein of

SARS-CoV-2 does not have an amino acidSubstitution compared to that of SARS-CoV (16).

E Protein

The coronavirus E protein is the most enigmatic

And smallest of the major structural proteins (51). It 

plays a multifunctional role in the pathogenesis, 

assembly, and release of the virus (52). It is a small

Integral membrane polypeptide that acts as a 

viroporin (ion channel) (53). The inactivation or

Coronavirus S protein is a large, multifunctional

Class I viral transmembrane protein. The size of this

Abundant S protein varies from 1,160 amino acids

(IBV, infectious bronchitis virus, in poultry) to 1,400

Amino acids (FcoV, feline coronavirus) (43). It liesIn a trimer on the virion surface, giving the virion a

Corona or crown-like appearance. Functionally it is

Required for the entry of the infectious virion

Particles into the cell through interaction with 

various host cellular receptors (44).

Furthermore, it acts as a critical factor for tissue

Tropism and the determination of host range (45).

Notably, S protein is one of the vital

Immunodominant proteins of CoVs capable of 

inducing host immune responses (45). The

Ectodomains in al CoVs S proteins have similar

Domain organizations, divided into two subunits, S1 

and $2 (43). The first one, S1, helps in host receptor 

binding, while the second one, S2, accounts for 

fusion. The former (S1) is further divided into two

Subdomains, namely, the N-terminal domain (NTD)And C-terminal domain (CTD). Both of these 

subdomains act as receptor-binding domains, 

interacting efficiently with various host receptors 

(45). The S1 CTD contains the receptor-binding

Motif (RBM). In each coronavirus spike protein, the 

trimeric S1 locates itself on top of the trimeric S2

NCVCTUicicss, 1OT

CIVCL

Cat and camels, respectively, act as amplifier hosts

(40, 41).

Coronavirus genomes and subgenomes encode

Six ORFs (31). The majority of the 5’ end is occupied 

by ORFla/b, which produces 16 nsps. The two 

polyproteins, ppla and pplab, are initially produced from ORFla/b by a -1 frameshift between ORFla and 

ORF1b (32). The virus-encoded proteases cleave

Polyproteins into individual nsps (main protease

[Mpro], chymotrypsin-like protease [3Clpro], and

Papain-like proteases [PLPs)) (42). SARS-CoV-2 also 

encodes these nsps, and their functions have been 

elucidated recently (31). Remarkably, a

Difference between SARS-CoV-2 and other CoVs is

The identification of a novel short putative protein

Within the ORF3 band, a secreted protein with an

Alpha helix and beta-sheet with six strands encoded

By ORF8 (31).

Coronaviruses encode four major structural

Proteins, namely, spike (S), membrane (M), envelope 

(E), and nucleocapsid (N), which are described inDetail below.

S Glycoprotein

Coronavirus S protein is a large, multifunctional

Class I viral transmembrane protein. The size of this

Based on molecular characterization, SARS

CoV-2 is considered a new Betacoronavirus

Belonging to the subgenus Sarbecovirus (3). 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(ORFla/b) is below 90% identity (3). 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 (2, 31, 36). In addition, 82%

Identity has been observed between SARS-CoV-2

And human SARS-CoV Tor2 and human SARS-CoV

BJO1 2003 (31). A sequence identity of only 51.8%

Was observed between MERS-related CoV and the

Recently emerged SARS-CoV-2 (37). 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 aRole in disease transmission to humans (31). Of 

note,

The other two zoonotic CoVs (MERS-related CoV

And SARS-related CoV) also originated from bats

(38, 39). Nevertheless, for SARS and MERS, civet

Encircled with an envelope containing Viral

Nucleocapsid. The nucleocapsids in CoVs are

Arranged in helical symmetry, which reflects an 

atypical attribute in positive-sense RNA viruses (30). 

The electron micrographs of SARS-CoV-2 revealed a 

diverging spherical outline with some degree of

Pleomorphism, virion diameters varying from 60 to

140 nm, and distinct spikes of 9 to 12 nm, giving the 

virus the appearance of a solar corona (3). The CoV genome is arranged linearly as 5-leader-UTR- 

replicase-structural genes (S-E-M-N)-3’ UTR- poly(A) 

(32). Accessory genes, such as 3a/b, 4a/b,

And the hemagglutinin-esterase gene (HE), are also

Seen intermingled with the structural genes (30).

SARS-CoV-2 has also been found to be arranged

Similarly and encodes several accessory

proteinS,

although it lacks the HE, which is characteristic of

betacoronaviruses (31). The positive-sense

some

genome of CoVs serves as the mRNA and is

translated to polyprotein la/lab (ppla/lab) (33). A

replication-transcription complex (RTC) is formed indouble-membrane vesicles (DMVs) by nonstructural

proteins (nsps), encoded by the polyprotein gene

(34). Subsequently, the RTC synthesizes a nested set 

of subgenomic RNAs (sgRNAs) via discontinuous

Transcription (35).

Wiought havoc in China and caused a pandemic

Situation in the worldwide population, leading to

Disease outbreaks that have not been controlled to

Date, although extensive efforts are being put in 

place to counter this virus (25). This virus has been 

proposed to be designated/named severe acute 

respiratory syndrome coronavirus 2 (SARS-CoV-2)

By the International Committee on Taxonomy of

Viruses (ICTV), which determined the virus belongs

To the Severe acute respiratory syndrome-relatedCoronavirus category and found this virus is related

To SARS-CoVs (26). SARS-CoV-2 is a member of the 

order Nidovirales, family Coronaviridae,

Subfamily Orthocoronavirinae, which is subdivided

Into

Four

Viz.,

Alphacoronavirus,

Genera,

Betacoronavirus,

Gammacoronavirus,

And

(3, 27).

Deltacoronavirus

The

Genera

Alphacoronavirus and Betacoronavirus originate

From

Bats,

While Gammacoronavirus

And

Deltacoronavirus have evolved from bird and swine

Gene pools (24, 28, 29, 275).

Coronaviruses possess an unsegmented, single-

Stranded, positive-sense RNA genome of around 30 

kb, enclosed by a 5-cap and 3-poly(A) tail (30). The 

genome of SARS-CoV-2 is 29,891 bp long, with a G+C 

content of 38% (31). These viruses areEncircled with an envelope containing viral

Some therapeutic options for treating COVID-19 

showed efficacy in in vitro studies; however, to date,

These treatments have not undergone any 

randomized

Animal or human clinical trials, which limit their

Practical applicability in the current pandemic (7, 9, 

19-21).

The present comprehensive review describes the

Various features of SARS-CoV-2/COVID-19 causing

The current disease outbreaks and advances in the

Diagnosis and developing vaccines and therapeutics.

It also provides a brief comparison with the earlierSARS and MERS CoVs, the veterinary perspective

Of CoVs and this emerging novel pathogen, and an 

evaluation of the zoonotic potential of similar CoVs

To provide feasible One Health strategies for the

Management of this fatal virus (22-367).

THE VIRUS (SARS-CoV-2)

Coronaviruses are positive-sense RNA viruses

Range of

Having an extensive and promiscuous

Natural hosts and affect multiple systems (23, 24).

Coronaviruses can cause clinical diseases in humans

That may extend from the common cold to more

Severe respiratory diseases like SARS and MERS(17, 279). The recently emerging SARS-CoV-2 has 

wrought havoc in China and caused a pandemic 

situation in the worldwide nonulation leadino to

Furthermore, SARS-CoV-2 is genetically distinct from 

SARS-CoV (79% similarity) and MERS-CoV (nearly 

50%) (17). COVID-19 is associated with afflictions of 

the lungs in all cases and generated characteristic 

chest computer tomography findings, such as the 

presence of multiple lesions in lung lobes

That appear as dense, ground-glass opaque 

structures

That occasionally coexist with consolidation shadows

(18).

New targeted drugs, and prevention of further 

epidemics (13). The most common symptoms 

associated with COVID-19 are fever, cough, dyspnea, 

expectoration, headache, and myalgia or fatigue.In contrast, less common signs at the time of 

hospital admission include diarrhea, hemoptysis, and 

shortness of breath (14). Recently, individuals with 

asymptomatic infections were also suspected of 

transmitting infections, which further adds to the 

complexity of disease transmission dynamics in 

COVID-19 infections (1). Such efficient responses

Require in-depth knowledge regarding the virus,

Which currently is a novel agent; consequently,

Further studies are required.

Comparing the genome of SARS-CoV-2 with that

Of the closely related SARS/SARS-like CoV

Revealed that the sequence coding for the spike 

protein, with a total length of 1,273 amino acids,

Showed 27 amino acid substitutions. Six of these

Substitutions are in the region of the receptor-

bindingDomain (RBD), and another six substitutions are in

The underpinning subdomain (SD) (16). Phylogenetic 

analyses have revealed that SARS-CoV-2 is closely

Related (88% similarity) to two SARS-like CoVs

Derived from bat SARS-like CoVs (bat-SL- CoVZC45 

andbat-SL-CoVZXC21) (Fig.

Range of hosts, producing symptoms and diseases

Ranging from the common cold to severe and

Ultimately fatal illnesses, such as SARS, MERS, and,

Presently, COVID-19. SARS-CoV-2 is considered one 

of the seven members of the CoV family that

Infect humans (3), and it belongs to the same lineage

Of CoVs that causes SARS; however, this novel virusIs genetically distinct. Until 2020, six CoVs were

Known to infect humans, including human CoV 229E

(HC%V-229E), HcoV-NL63, HcoV-OC43, HcoV-

HKUI, SARS-CoV, and MERS-CoV. Although

SARS-CoV and MERS-CoV have resulted in

Outbreaks with high mortality, others remain

Associated with mild upper-respiratory-tract 

illnesses

(4).

Newly evolved CoVs pose a high threat to global

Public health. The current emergence of COVID-19

Is the third CoV outbreak in humans over the past 2

Decades (5). It is no coincidence that Fan et al.Predicted potential SARS- or MERS-like CoV

Outbreaks in China following pathogen transmission

From bats (6). COVID-19 emerged in China and

Spread rapidly throughout the country and, 

subsequently, to other countries. Due to the severity

Of this outbreak and the potential of spreading on 

an international scale, the WHO declareda global

Health emeroencv on 31 Tanuarv 2020: 

subseauentlv

Health emergency on 31 January 2020; 

subsequently,

On 11 March 2020, they declared it a pandemic

Situation. At present, we are not in a position to

Effectively treat COVID-19, since neither approvedVaccines nor specific antiviral drugs for treating

Human CoV infections are available (7-9). Most

Nations are currently making efforts to prevent the

Further spreading of this potentially deadly virus by

Implementing preventive and control strategies.

In domestic animals, infections with CoVs are

Associated with a broad spectrum of pathological

Conditions. Apart from infectious bronchitis virus,

Canine respiratory CoV, and mouse hepatitis virus,

CoVs

Predominantly associated with

Are

Gastrointestinal diseases (10). The emergence ofNovel CoVs may have become possible because of

Multiple CoVs being maintained in their natural host,

Which could have favored the probability of genetic

Recombination (10). High genetic diversity and the

Ability to infect multiple host species are a result of

High-frequency mutations in CoVs, which occur due 

to the instability of RNA-dependent RNA

Polymerases along with higher rates of homologous 

RNA recombination (10, 11). Identifying the origin of 

SARS-CoV-2 and the pathogen’s evolution will be 

helpful for disease surveillance (12), development of

Coronaviruses in Humans SARS, MERS,

And COVID-19Coronavirus infection in humans is commonly

Associated with mild to severe respiratory diseases,

With high fever, severe inflammation, cough, and

Internal organ dysfunetion that can even lead to

Death (92). Most of the identified coronaviruses

Cause the common cold in humans. However, this

Changed when SARS-CoV was identified, paving the

Way for severe forms of the disease in humans (22). 

Our previous experience with the outbreaks of other

Coronaviruses, like SARS and MERS, suggests that 

the mode of transmission in COVID-19 as mainly

Human-to-human transmission via direct contact,

Droplets, and fomites (25). Recent studies have

Demonstrated that the virus could remain viable forHours in aerosols and up to days on surfaces; thus, 

aerosol and fomite contamination could play potent 

roles in the transmission of SARS-CoV-2 (257).

The immune response against coronavirus is vital

To control and get rid of the infection. However,

Maladjusted immune responses may contribute to 

the immunopathology of the disease, resulting in

Impairment

Of pulmonary

Exchange.

Gas

Understanding the interaction between CoVs and

Host innate immune systems could enlighten our

Understanding of the lung inflammation associatedWith this infection (24).

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 (90). The SARS

Outbreak reported in 2002 to 2003 had 8,098

Confirmed cases with 774 total deaths (9.6%) (93).

The outbreak severely affected the Asia Pacific 

region, especially mainland China (94). 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(95, 279). This can fail the public health system,

Resulting in a pandemic (96). MERS is another 

respiratory disease that was first reported in Saudi 

Arabia during the year 20112.

The disease was found to have a CFR of around 35%

(97). 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 (98).

Even though a high similarity has been reported

Even though a high similarity has been reported

Between the genome sequence of the newCoronavirus (SARS-CoV-2) and SARS-like CoVs,

The

Comparative analysis recognized a furin-like

Cleavage site in the SARS-CoV-2 S protein that is

Missing from other SARS-like CoVs (99). The furin- 

like cleavage site is expected to play a role in the life 

cycle of the virus and disease pathogenicity and

Might even act as a therapeutic target for furin 

inhibitors. The highly contagious nature of SARS-

CoV-2 compared to that of its predecessors might be

The result of a stabilizing mutation that occurred in

The endosome-associated-protein-like domain of

Nsp2 protein. Similarly, the destabilizing mutation 

near the phosphatase domain of nsp3 proteins in 

SARS-CoV- 2 could indicate a potential mechanism 

that2

Differentiates it fronm other CoVs (100). Even 

though

The CFR reported for COVID-19 is meager compared 

to those of the previous SARS and MERS

Outbreaks, it has caused more deaths than SARS and

MERS combined (101). Possibly related to the viral

Pathogenesis is the recent finding of an 832- 

nucleotide (nt) deletion in ORF8, which appears to

Reduce the replicative fitness of the virus and leads 

to attenuated phenotypes of SARS-CoV-2 (256). 

Coronavirus is the most prominent example of a

TiatkeLS, pionoteu iurtier adaptatiOns uial TesuitCd

In the epidemic strain (I04). Transmission can alsoOccur directly from the reservoir host to humans

Without RBD adaptations. The bat coronavirus that 

is

Currently in circulation maintains specific “poised”

Spike proteins that facilitate human infection 

without

The requirement of any mutations or adaptations 

(105). Altogether, different species of bats carry a

Massive number of coronaviruses around the world

(106).

The high plasticity in receptor usage, along with the 

feasibility of

Adaptive mutation and

Recombination, may result in frequent interspecies

Transmission of coronavirus from bats to animals 

andHumans (106). The pathogenesis of most bat

Coronaviruses is unknown, as most of these viruses

Are not isolated and studied (4). Hedgehog

Are

Coronavirus HKU31, a Betacoronavirus, has been

Identified from amur hedgehogs in China. Studies

Show that hedgehogs are the reservoir of

Betacoronavirus, and there is evidence of

Recombination (107).

The current scientific evidence available on

MERS infection suggests that the significant

Reservoir host, as well as the animal source of MERS

Infection in humans, is the dromedary camels (97).The infected dromedary camels may not show any 

visible signs of infection. Makingit challenging to

Populaions. The vilro and VivO Sludies carrieu

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 (105).

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 superiorTransmission 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 (112). The mean

Incubation period of COVID-19 was found to be 6.4

Days, ranging from 2.1 to 11.1 days (113). Among an 

early affected group of 425 patients, 59 years was 

the

Median age, of which more males were affected

(114). Similar to SARS and MERS, the severity of this 

nCoV is high in age groups above 50 years (2, 115). 

Symptoms of COVID-19 include fever, cough,

Myalgia or fatigue, and, less commonly, headache,

Hemoptysis, and diarrhea (116, 282). Compared to 

the SARS-CoV-2-infected patients in Wuhan duringThe 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 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). Regardless of

The coronavirus type, immune cells, like mast cells, 

that are present in the submucosa of the respiratoryTract and nasal cavity are considered the primary

Barrier against this virus (92). Advanced in-depth

Analysis of the genome has identified 380 amino 

acid

Substitutions between the amino acid sequences of

SARS/SARS-like

SARS-CoV-2

And the

Coronaviruses. 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

Tropism,In

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

VISible signs of infection, making it challengng to

Identify animals actively excreting MERS-CoV that

Has the potential to infect humans. However, they 

may shed MERS-CoV through milk, urine, feces,And nasal and eye discharge and can also be found 

in

The raw organs (108). In a study conducted to

Evaluate the susceptibility of animal species to

MERS-CoV infection, llamas and pigs were found to 

be susceptible, indicating the possibility of MERS- 

CoV circulation in animal species other than

Dromedary camels (109).

Following the outbreak of SARS in China,

SARS-CoV-like viruses were isolated from

Himalayan palm civets (Paguma larvata) and raccoon 

dogs (Myctereutes procyonoides) found in a

The

Live-animal market in Guangdong, China. The

Animal isolates obtained from the live-animal 

marketRetained a 29-nucleotide sequence that was not 

present in most of the human isolates (78). These

Findings were critical in identifying the possibility of 

interspecies transmission in SARS-CoV. The higher

Diversity and prevalence of bat coronaviruses in this

Region compared to those in previous reports 

indicate host/pathogen

SARS-like

Coevolution.

A

Coronaviruses also have been found circulating in 

the Chinese horseshoe bat (Rhinolophus sinicus)

Populations. The in vitro and in vivo studies carried

Only a matter of time before another zoonoticCoronavirus results in an epidemic by jumping the

So-called species barrier (287).

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) (138). 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 (30). 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 mammalianSpecies (6). 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 effīicient 

molecular surveillance strategies for studying

Betacoronavirus among animals (12), especially in

The Rhinolophus bat family (86). Chinese bats have 

high commercial value, since they are used in

dsyiiipWIlidu

SyiiipiULlialit

Pautils1laviiiyS

Minimum signs and symptoms (82). Another study,

Conducted in South Korea, related to SARS-CoV-2

Viral load, opined that SARS-C%V-2 kinetics were

Significantly different from those of earlier reported 

CoV infections, including SARS-CoV (253). SARS- CoV-

2 transmission can occur early in the viral

Infection phase; thus, diagnosing cases and isolation

Attempts for this virus warrant different strategies

Than those needed to counter SARS-CoV. Studies are

Required to establish any correlation between SARS- 

CoV-2 viral load and cultivable virus. Recognizing

Patients with fewer or no symptoms, along with

Having modest detectable viral RNA in the

Oropharynx for 5 days, indicates the requirement ofData for assessing SARS-CoV-2 transmission 

dynamics and updating the screening procedures in

The clinics (82).

Significance of frequent and good hand hygiene and

Sanitation practices needs to be given due emphasis

(249-252). Future explorative research needs to be

Conducted with regard to the fecal-oral transmission

Of SARS-CoV-2, along with focusing on

Environmental investigations to find out if this virus 

could stay viable in situations and atmospheres

Facilitating such potent routes of transmission. The

Correlation of fecal concentrations of viral RNA withDisease severity needs to be determined, along with 

assessing the gastrointestinal symptoms and the

Possibility of fecal SARS-CoV-2 RNA detection

During the COVID-19 incubation period or 

convalescence phases of the disease (249-252). The 

lower respiratory tract sampling techniques,

Like bronchoalveolar lavage fluid aspirate, are

Considered the ideal clinical materials, rather than

The throat swab, due to their higher positive rate on 

the nucleic acid test (148). The diagnosis of COVID-

19 can be made by using upper-respiratory-tract

Specimens collected using nasopharyngeal and

Oropharyngeal swabs. However, these techniques 

are

Associated with unnecessary risks to health care

Workers due to close contact with patients (152).Similarly, a single patient with a high viral load was

Reported to contaminate an entire endoscopy rom 

by

Shedding the virus, which may remain viable for at

A suspected case of COVID-19 infection is said to be 

confirmed if the respiratory tract aspirate or blood 

samples test positive for SARS-CoV-2 nucleic acid 

using RT-PCR or by the identification of SARS

CoV-2 genetic sequence in respiratory tract aspirate

Or blood samples (80). The patient will be confirmed

As cured when two subsequent oral swab results are

Negative (153). Recently, the live virus was detected 

in the self-collected saliva of patients infected with

COVID-19. These findings were confirmative ofUsing saliva as a noninvasive specimen for the

Diagnosis of COVID-19 infection in suspected 

individuals (152). It has also been observed that the

Initial screening of COVID-19 patients infected with 

RT-PCR may give negative results even if they have

Chest CT findings that are suggestive of infection. 

Hence, for the accurate diagnosis of COVID-19, a 

combination of repeated swab tests using RT-PCR

And CT scanning is required to prevent the 

possibility of false-negative results during disease

Screening (154). RT-PCR is the most widely used test

For diagnosing COVID-19. However, it has some

Significant limitations from the clinical perspective,

Since it will not give any clarity regarding disease 

progression. Droplet digital PCR (ddPCR) can be used 

for the quantification of viral load in theSamples obtained from lower respiratory tracts.

Shedding the virus, which may remain viable for at

Least 3 days and is considered a great risk for

Uninfected patients and health care workers (289). 

Recently, it was found that the anal swabs gave 

more

Positive results than oral swabs in the later stages of

Infection (153). Hence, clinicians have to be cautious

While discharging any COVID-19-infected patient

Based on negative oral swab test results due to the 

possibility of fecal-oral transmission. Even though

The viral loads in stool samples were found to be 

less

Than those of respiratory

StrictSamples,

Precautionary measures have to be followed while 

handling stool samples of COVID-19 suspected or

Infected patients (151). Children infected with

SARS-CoV-2 experience only a mild form of illness

Recover immediately after treatment. It was

And

Recently found that stool samples of SARS-CoV-2-

Infected children that gave negative throat swab

Results were positive within ten days of negative

This could result in the fecal-oral

Results.

Transmission of SARS-CoV-2 infections, especiallyIn children (290). Hence, to prevent the fecal-oral

Transmission of SARS-CoV-2, infected COVID-19

Patients should only be considered negative when 

test negative for SARS-CoV-2 in the stool

They

Sample.

Fluid,

Specimens, like bronchoalveolar lavage fluid,

Sputum, nasal swabs, fibrobronchoscope brush 

biopsy specimens, pharyngeal swabs, feces, and 

blood (246).

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, suchAs fecal excretion and environmental and fomite

Contamination, are contributing to SARS-CoV-2 

transmission and spread (249-252). Fecal excretion

Has also been documented for SARS-CoV and has

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

(249-252). Appropriate precautions need to be

Followed strictly while handling the stools of 

patientsInfected 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 results of the studies related to SARS-CoV-2

Viral loads reflect active replication of this virus in

The upper respiratory tract and prolonged viral

Shedding after symptoms disappear, including via

Stool. Thus, the current case definition needs to be

Updated along with a reassessment of the strategies

To be adopted for restraining the SARS-CoV-2

Outbreak spread (248). In some cases, the viral load

Studies of SARS-CoV-2 have also been useful toRecommend precautionary measures when handling 

specific samples, e.g., feces. In a recent survey from

17 confirmed cases of SARS-CoV-2 infection with

Available data (representing days 0 to 13 after 

onset), stool samples from nine cases (53%; days 0 

to 11 after onset) were positive on RT-PCR analysis.

Although the viral loads were lower than those of

Respiratory samples (range, 550 copies per ml to

1.21 x 10 copies per ml), this has essential biosafety

Implications (151).

The samples from 18 SARS-CoV-2-positive

Patients in Singapore who had traveled from Wuhan

To Singapore showed the presence of viral RNA in

Stool and whole blood but not in urine by real-timeRT-PCR (288). Further, novel SARS-CoV-2

Infections have been detected in a variety of clinical 

specimens, like bronchoalveolar lavage fluid,

Performance (Table 2) (80, 245, 246). The viral loads 

of SARS-CoV-2 were measured using N-gene-

Specific quantitative RT-PCR in throat swab and

Sputum samples collected from COVID-19-infected

Individuals. The results indicated that the viral load

Peaked at around 5 to 6 days following the onset of

Symptoms, and it ranged from 10* to 10 copies/ml 

during this time (151). In another study, the viral 

load was found to be higher in the nasal swabs than

The throat swabs obtained from COVID-19

Symptomatic patients (82). Although initially it was 

thought that viral load would be associated with 

poor

Outcomes, some case reports have shownAsymptomatic individuals with high viral loads (247). 

Recently, the viral load in nasal and throat swabs of 

17 symptomatic patients was determined,

And higher viral loads were recorded soon after the

Onset of symptoms, particularly in the nose 

compared to the throat. The pattern of viral nucleic 

acid shedding of SARS-CoV-2-infected patients was 

similar to that of influenza patients but seemed to 

be

Different from that of SARS-CoV patients. The viral

Load detected in asymptomatic patients resembled

That of symptomatic patients as studied in China,

Which reflects the transmission perspective of

Having

Asymptomatic or symptomatic patients having 

minimum signs and symptoms (82). Another study,Recently, 95 full-length genomic sequences of

SARAS-CoV-2 strains available in the National

Center for Biotechnology Information and GISAID

Databases were subjected to multiple-sequence

Alignment and phylogenetic analyses for studying

Variations in the viral genome (260). All the viral 

strains revealed high homology of 99.99% (99.91% 

to 100%) at the nucleotide level and 99.99%

(99.79% to 100%) at the amino acid level. Overal

Variation was found to be low in ORF regions, with 

13 variation sites recognized in la, 1b, S, 3a, M, 8, 

and N regions. Mutation rates of 30.53% (29/95) and

29.47% (28/95) were observed at nt 28144 (ORF8)

And nt 8782 (ORFla) positions, respectively. Owing

To such selective mutations, a few specific regions ofSARS-CoV-2 should not be considered for designing

Primers and probes. The SARS-CoV-2 reference

Sequence could pave the way to study molecular 

biology and pathobiology, along with developing

Diagnostics and appropriate prevention and control

Strategies for countering SARS-CoV-2 (260).

Nucleic acids of SARS-CoV-2 can be detected

From samples (64) such as bronchoalveolar lavage

Fluid, sputum, nasal swabs, fiber bronchoscope 

brush

Biopsy specimen, pharyngeal swabs, feces, blood, 

and urine, with different levels of diagnostic

Performance (Table 2) (80, 245, 246). The viral loads

DIAGNOSIS OF SARS-CoV-2 (COVID19)

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). 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). 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). Up to 30 March 2020, the U.S. Food and DrugAdministration (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 betacoronaviruses

And specific detection of SARS-CoV-2, developed

By the U.S. CDC (Table 1) (258, 259).

Dogs have loW susceplubility, while the chickens,

Ducks, and pigs are not at all susceptible to SARS- 

CoV-2 (329).

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 

asymptomaticZookeeper (335). 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 (336). However,

Experimental inoculation with SARS-CoV-2 failed to 

infect pigs (329).

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 thePossible risk factors of transmission between 

animals

And humans. Such cooperation will help to devise

Efficient strategies for the management of emerging

Zoonotic diseases (12).

Infected by human beings. However, evidence of 

cat-

To-human transmission is lacking and requires 

further studies (332). Rather than waiting for firmer

On animal-to-human

Evidence

Transmission,

Necessary preventive measures are advised, as wellAs following social distancing practices among 

companion animals of different households (331).

One of the leading veterinary diagnostic companies, 

IDEXX, has conducted large-scale testing for

COVID-19 in specimens collected from dogs and

Cats. However, none of the tests turned out to be

Positive (334). In a study conducted to investigate 

the potential of different animal species to act as the 

intermediate

Host of SARS-CoV-2, it was found that both ferrets

And cats can be infected via experimental 

inoculation

Of the virus. In addition, infected cats efficiently 

transmitted the disease to naive cats (329). SARS-

CoV-2 infection and subsequent transmission in

Ferrets were found to recapitulate the clinical 

aspectsOf COVID-19 in humans. The infected ferrets also

Shed virus via multiple routes, such as saliva, nasal

Washes, feces, and urine, postinfection, making 

them an ideal animal model for studying disease

Transmission (337). Experimental inoculation was

Also done in other animal species and found that the

Dogs have low susceptibility, while the chickens,

These findings will not have any significance until a

Significant outbreak occurs due to a virus-like

SARS-CoV-2.

There

Is a steady increase in the reports of

COVID-19 in companion and wild animals aroundThe world. Further studies are required to evaluate

The potential of animals (especially companion

Animals) to serve as an efficient reservoir host that

Can further alter the dynamics of human-to-human

Transmission (330). To date, two pet dogs (Hong

Kong) and four pet cats (one each from Belgium and

Hong Kong, two from the United States) have tested

Positive for SARS-CoV-2 (335). The World 

Organization for Animal Health (OIE) has confirmed

The diagnosis of COVID-19 in both dogs and cats

Due to human-to-animal transmission (331). The

Similarity observed in the gene sequence of SARS-

CoV-2 from an infected pet owner and his dogFurther confirms the occurrence of human-to-animal

Transmission (333). Even though asymptomatic, 

feline species should be considered a potential 

transmission route from animals to humans (326).

However, currently, there are no reports of SARS-

CoV-2 transmission from felines to human beings.

Based on the current evidence, we can conclude that

Cats are susceptible to SARS-CoV-2 and can get

Infected by human beings. However, evidence of 

cat-

(96.7 %), and S genes (90.4 %). The RBD of S protein 

in CoV isolated from pangolin was almost identical

(one amino acid difference) to that of SARS-CoV-2.

A comparison of the recombination between 

pangolin-CoV-like viruses

Suggests

Genomes

This with the bat-CoV-RaTG13-like virus. All this

Suggests the potential of pangolins to act as the

Intermediate host of SARS-CoV-2 (145).

Interactions,

Human-wildlife

Which

Are

Increasing in the context of climate change (142), are

Further eonsidered high risk and responsible for the 

emergence of SARS-CoV. COVID-19 is also suspected 

of having a similar mode of origin. Hence, to prevent the occurrence of another zoonotic spillover (1), 

exhaustive coordinated efforts

Are

Needed to identify the high-risk pathogens harbored

By wild animal populations, conducting surveillance

Among the people who are susceptible to zoonotie

Spillover events (12), and to improve the biosecurity

Measures associated with the wildlife trade (146).

The serological surveillance studies conducted in

People living in proximity to bat caves had earlier

Identified the serological confirmation of SARS- 

related CoVs in humans. People living at the

Wildlife-human interface, mainly in rural China, are

Regularly exposed to SARS-related CoVs (147). These 

findings will not have any significance until aThe compreliensive sequence analySis of the

SARS-CoV-2 RNA genome identified that the CoV

From Wuhan is a recombinant virus of the bat

Coronavirus and another coronavirus of unknown

Origin. The recombination was found to have 

happened within the viral spike glycoprotein, which 

recognizes the cell surface receptor. Further analysis

Of the genome based on codon usage identified the

Snake as the most probable animal reservoir of 

SARS-CoV-2 (143). Contrary to these findings, 

another genome analysis proposed that the genome

Of SARS-CoV-2 is 96% identical to bat coronavirus,

Reflecting its origin from bats (63). The involvement 

of bat-derived materials in causing the currentOutbreak cannot be ruled out. High risk is involved

In the production of bat-derived materials for TCM

Practices involving the handling of wild bats. The use 

of bats for TCM practices will remain a severe

Risk for the occurrence of zoonotic coronavirus

Epidemics in the future (139).

Furthermore, the pangolins are an endangered

Species of animals that harbor a wide variety of

Viruses, including coronaviruses (144). The 

coronavirus isolated from Malayan pangolins (Manis 

javanica) showed a very high amino acid identity

With COVID-19 at E (100%), M (98.2%), N (96.7%), 

and S genes (90.4%). The RBD of S protein

High commercial value, since they are used m

Traditional Chinese medicine (TCM). Therefore, theHandling of bats for trading purposes poses a 

considerable risk of transmitting zoonotic CoV 

epidemics (139). 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 (25). 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 (78). Such markets can be considered a

Critical place for the origin of novel zoonotic diseases 

and have enormous public health

Significance in the event of an outbreak. Bats are the

Reservoirs for several viruses; hence, the role of batsIn the present outbreak cannot be ruled out (140). In 

a qualitative study conducted for evaluating the

Zoonotic risk factors among rural communities of

Southern China, the frequent human-animal along 

with the low levels of

Interactions

Environmental biosecurity were identified as

Significant risks for the emergence of zoonotic

Disease in local communities (141, 142).

The comprehensive sequence analysis of the

Swine acute diarrhea syndrome coronavirus

(SADS-CoV) was first identified in suckling piglets

Having severe enteritis and belongs to the genus

The outbreak wasAlphacoronavirus (106).

Associated with considerable scale mortality of 

piglets (24,693 deaths) across four farms in China

(134). The virus isolated from the piglets was almost

Identical to and had 95% genomic similarity with

Horseshoe bat (Rhinolophus species) coronavirus 

HKU2, suggesting a bat origin of the pig virus (106, 

134, 135). It is also imperative to note that the

SADS-CoV outbreak started in Guangdong province, 

near the location of the SARS pandemic origin

(134). Before this outbreak, pigs were not known to

Be infected with bat-origin coronaviruses. This 

indicates that the bat-origin coronavirus jumped to

Pig by breaking the species barrier. The next step of

This jump might not end well, since pigs are 

considered the mixing vessel for influenza A virusesDue to their ability to be infected by both human 

and

Avian influenza A viruses (136).

Similarly, they may act as the mixing vessel for

Coronaviruses, since they are in frequent contact 

with both humans and multiple wildlife species.

Additionally, pigs are also found to be susceptible to

Infection with human SARS-CoV and MERS-CoV,

Making this scenario a nightmare (109, 137). It is

System (30).

Bovine coronaviruses (BoCoVs) are known to

Infect several domestic and wild ruminants (126).

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). BoCoV-like viruses 

have been noted in humans, suggesting its zoonotic

Potential as well (127). 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).

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 (129, 130). IBV,Under Gammacoronavirus, causes diseases of

Respiratory, urinary, and reproductive systems, with 

substantial economic losses in chickens (131, 132).

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). Swine 

acute diarrhea syndrome coronavirus

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 infectionsIn humans (30).

Among the CoV genera, Alphacoronavirus and

Infect

Betacoronavirus

While

Mammals,

Gammacoronavirus and Deltacoronavirus mainly 

infect birds, fishes, and, sometimes, mammals (27,

29, 106). 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 coronavirusHKU16, night-heron coronavirus HKU19, and

Common moorhen coronavirus HKU21, as well as

From pigs (porcine coronavirus HKU15) (6, 29). 

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

Amnotransferase, bilirubin, and, especially, D-dimer

(244). Middle-aged and elderly patients with primaryChronic diseases, especially high blood pressure and 

diabetes, were found to be more susceptible to

Respiratory failure and, therefore, had poorer

Prognoses. Providing respiratory support at early

Stages improved the disease prognosis and 

facilitated

In occurrence of cytokine storms that results in

Recovery (18). The ARDS in COVID-19 is due to the

Exaggerated immune response, immune regulatory

Network imbalance, and, finally, multiple-organ 

failure (122). In addition to the exaggerated 

inflammatory response seen in patients with

COVID-19 pneumonia, the bile duct epithelial cell 

derived hepatocytes upregulate ACE2 expression in 

liver tissue by compensatory proliferation that might 

result in hepatic tissue injury (123).

CORONAVIRUSES IN ANIMALS ANDZOONOTIC LINKS-A BRIEF

VIEWPOINT

Coronavirus can cause disease in several species

Of domestic and wild animals, as well as humans

(23). The different animal species that are infected 

with CoV include horses, camels, cattle, swine, dogs,

Cats, rodents, birds, ferrets, minks, bats, rabbits,

Snakes, and various other wild animals (20, 30, 79,

SARS-

Or MERS-CoV outbreak (120). However,

There has been concern regarding the impact of

SARS-CoV-2/COVID-19 on pregnancy. Researchers 

have mentioned the probability of in uteroTransmission 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 (283). 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 (240-243).

COVID-19 infection was associated withPneumonia, and some developed acute respiratory

Distress syndrome (ARDS). The blood biochemistry

Indexes, such as albumin, lactate dehydrogenase, C-

Lymphocytes (percent),

Reactive protein, neutrophils (percent) give an idea 

about the disease

And

Severity in COVID-19 infection (121). During COVID-

19, patients may present leukocytosis,

Leukopenia

With

(244),

LymphopeniaHypoalbuminemia, and an increasee of lactate 

dehydrogenase, aspartate transaminase, alanine 

aminotransferase, bilirubin, and, especially, D-dimer

1A

With SARS and MERS (117).

SARS-CoV-2 invades the lung parenchyma, resulting 

in severe interstitial inflammation of the

Lungs. This is evident on computed tomography (CT) 

images as ground-glass opacity in the lungs. This 

lesion initially involves a single lobe but later

Expands to multiple lung lobes (118). The histological 

assessment of lung biopsy samples

The

Obtained from COVID-19-infected patients revealed

Diffuse alveolar damage, cellular fibromyxoid 

exudates, hyaline membrane formation, andDesquamation of pneumocytes, indicative of acute

Respiratory distress syndrome (119). It was also

Found that the SARS-CoV-2-infected patients often

Have lymphocytopenia with or without leukocyte 

abnormalities. The degree of lymphocytopenia give 

an idea about disease prognosis, as it is found to be

Positively correlated with disease severity (118).

Pregnant women are considered to have a higher 

risk

Of getting infected by COVID-19. The coronaviruses

Can cause adverse outcomes for the fetus, such as

Intrauterine growth restriction, spontaneous 

abortion,

Preterm delivery, and perinatal death.

Nevertheless, the possibility of intrauterineMaternal-fetal transmission (vertical transmission) of

CoVs is low and was not seen during either the

SARS- or MERS-CoV outbreak (120). However,

CoronaVirus is the most prominent example of a

Virus that has crossed the species barrier twice from

Wild animals to humans during SARS and MERS

Outbreaks (79, 102). The possibility of crossing the

Species barrier for the third time has also been 

suspected in the case of SARS-CoV-2 (COVID-19).

Bats are recognized as a possible natural reservoir

Host of both SARS-CoV and MERS-CoV infection.

In contrast, the possible intermediary host is the 

palm civet for SARS-CoV and the dromedary camel

For MERS-CoV infection (102). Bats are consideredThe ancestral hosts for both SARS and MERS (103).

Bats are also considered the reservoir host of human

Coronaviruses like HcoV-229E and HcoV-NL63

(104). In the case of COVID-19, there are two

Possibilities for primary transmission: it can be

Transmitted either through intermediate hosts, 

similar

To that of SARS and MERS, or directly from bats

(103). The emergence paradigm put forward in the 

SARS outbreak suggests that SARS-CoV originated

From bats (reservoir host) and later jumped to civets 

(intermediate host) and incorporated changes within

The receptor-binding domain (RBD) to improve 

binding to civet ACE2. This civet-adapted virus,

During their subsequent exposure to humans at liveMarkets, promoted further adaptations that resulted 

in the epidemic strain (104). Transmission can also

Samples obtained from lower respiratory tracts.

Hence, based on the viral load, we can quickly 

evaluate the progression of infection (291). In 

addition to all of the above findings, sequencing and

Phylogenetics are critical in the correct identification 

and confirmation of the causative viral agent and

Useful to establish relationships with previous

Isolates and sequences, as well as to know, 

especially

During an epidemic, the nucleotide and amino acid

Mutations and the molecular divergence. The rapidDevelopment and implementation of diagnostic 

tests

Against emerging novel diseases like COVID-19 pose 

significant challenges due to the lack of resources 

and logistical limitations associated with an outbreak 

(155).

SARS-CoV-2 infection can also be confirmed by 

isolation and culturing. The human airway epithelial 

cell culture was found to be useful in isolating SARS-

CoV-2 (3). The efficient control of an

Outbreak depends on the rapid diagnosis of the

Disease. Recently, in response to the COVID-19

Outbreak, 1-step quantitative real-time reverse 

transcription-PCR assays were developed that detect

The ORFlb and N regions of the SARS-CoV-2

Genome (156). That assay was found to achieve the

Rapid detection of SARS-CoV-2. Nucleic acid-basedAssays offer high accuracy in the diagnosis of SARS-

Been controlled by adopting appropriate and strict

Prevention and control measures, and patients for

Clinical trials will not be available. The newly

Developed drugs cannot be marketed due to the lack

Of end users.

Vaccines

The S protein plays a significant role in the induction 

of protective immunity against SARS-CoV by 

mediating T-cell responses and neutralizing

Antibody production (168). In the past few decades,

We have seen several attempts to develop a vaccine

Against human coronaviruses by using S protein asThe target (168, 169). However, the developed

Vaccines have minimal application, even among

Closely related strains of the virus, due to a lack of

Cross-protection. That is mainly because of the 

extensive diversity existing among the different 

antigenic variants of the virus (104). The

Contributions of the structural proteins, like spike

(S), matrix (M), small envelope (E), and nucleocapsid 

(N) proteins, of SARS-CoV to induce

Protective immunity has been evaluated by 

expressing them in a recombinant parainfluenza 

virus type 3 vector (BHPIV3). Of note, the result

Was conclusive that the expression of M, E, or N 

proteins without the presence of S protein would 

not

(181). CEPI has also funded Moderna to develop aVaccine for COVID-19 in partnership with the

Vaccine Research Center (VRC) of the National

Institute of Allergy and Infectious Diseases (NIAID), 

part of the National Institutes of Health (NIH) (182).

By employing mRNA vaccine platform technology, a

Vaccine candidate expressing SARS-CoV-2 spike 

protein is likely to go through clinical testing in the

Coming months (180). On 16 March 2020, Jennifer

Haller became the first person outside China to

Receive an experimental vaccine, developed by 

Moderna, against this pandemic virus. Moderna, 

along with China’s CanSino Biologics, became the 

first research group to launch small clinical trials of 

Their study is

Vaccines against COVID-19. Evaluating the vaccine’s 

safety and ability to trigger immune responses (296).Scientists from all over the world are trying hard

To develop working vaccines with robust protective

Immunity against COVID-19. Vaccine candidates,

Like mRNA-1273 SARS-CoV-2 vaccine, INO-4800

DNA coronavirus vaccine, and adenovirus type 5

Vector vaccine candidate (Ad5-nCoV), are a few

Examples under phase I clinical trials, while self 

amplifying RNA vaccine, oral recombinant COVID-

19 vaccine, BNT162, plant-based COVID-19

Vaccine, and Ii-Key peptide COVID-19 vaccine are

CETIICge w LUIT IVI

Administration of the recombinant adenovirus-based

Vaccine in BALB/c mice was found to induce long-Lasting neutralizing immunity against MERS spike

Pseudotyped virus, characterized by the induction of

Systemic IgG, secretory IgA, and lung-resident

Memory T-cell responses (177). Immunoinformatics 

methods have been employed for the genome-wide

Screening of potential vaccine targets among the

Different immunogens of MERS-CoV (178). The N 

protein and the potential B-cell epitopes of MERS- 

CoV E protein have been suggested as

Immunoprotective targets inducing both T-cell and 

neutralizing antibody responses (178, 179).

The collaborative effort of the researchers of

Rocky Mountain Laboratories and Oxford University

Is designing a chimpanzee adenovirus-vectored

Vaccine to counter COVID-19 (180). The CoalitionFor Epidemic Preparedness Innovations (CEPI) has 

initiated three programs to design SARS-CoV-2

Vaccines (181). CEPI has a collaborative project with 

Inovio for designing a MERS-CoV DNA vaccine

That could potentiate effective immunity. CEPI and 

the University of Queensland are designing a 

molecular clamp vaccine platform for MERS-CoV and 

other pathogens, which could assist in the easier

Identification of antigens by the immune system

(181). CEPI has also funded Moderna to develop a

Explored targeting molecular dynamic simulations,

Evaluating their interaction with corresponding 

major

Histocompatibility complex class I molecules. They

ThePotentially induce immune responses (176).

Recombinant vaccine can be designed by using 

rabies virus (RV) as a viral vector. RV can be made to

Express MERS-CoV S1 protein on its surface so that 

an immune response is induced against MERS-CoV.

The RV vector-based vaccines against MERS-CoV

Can induce faster antibody response as well as 

higher

Degrees of cellular immunity than the Gram-positive

Enhancer matrix (GEM) particle vector-based

Vaccine. However, the latter can induce a very high 

antibody response at lower doses (167). Hence, the

Degree of humoral and cellular immune responses

Produced by such vaccines depends upon the vector

Used.Dual vaccines have been getting more popular 

recently. Among them, the rabies virus-based 

vectored vaccine platform is used to develop 

vaccines against emerging infectious diseases. The

Dual vaccine developed from inactivated rabies virus

Particles that express the MERS-CoV S1 domain of S 

protein was found to induce immune responses for

Both MERS-CoV and rabies virus. The vaccinated

Mice were found to be completely protected from

Challenge with MERS-CoV (169). The intranasal

Might be lower. Further genetic analysıs is required

Between SARS-CoV-2 and different strains of

SARS-CoV and SARS-like (SL) CoVs to evaluate

TheThe 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.