2020 SCIENCELINE

O nline J ournal of A nimal and F eed R esearch

Volume 10, Issue 1: 01-11; January 25, 2020

ISSN 2228-7701

REVIEW ON CORONAVIRUS, A MIDDLE EAST

RESPIRATORY SYNDROME (MERS-CoV)



Berhanu KASSAHUN¹, Tilahun BERHANU²and Berhanu DAMTEW³

¹Jigjiga University, College of Veterinary Medicine, P.O.box 1030 jigjiga, Ethiopia

²Haramaya University,College of veterinary medicine, P.O.Box 138 Diredawa , Ethiopia

³Shirka veterinary clinic, Arsi, Ethiopia

^Email: kassahunberhanu110@gmail.com

^Supporting Information

ABSTRACT: Human coronaviruses (HCoVs) have long been considered in consequential pathogens, causing the

―common cold‖ in otherwise healthy people. However, in the 21^stcentury, 2 highly pathogenic HCoVs—severe

acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-

CoV)—emerged from animal reservoirs to cause global epidemics with alarming morbidity and mortality. In

December 2019, yet another pathogenic HCoV, 2019 novel coronavirus (2019-nCoV), was recognized in

Wuhan, China, and has caused serious illness and death. The ultimate cope and effect of this outbreak is

unclear at present as the situation is rapidly evolving. Middle East respiratory syndrome coronavirus (MERS-

CoV) is zoonotic diseases causing severe respiratory illness emerged in 2012 in Saudi Arabia. Phylogenetic

studies and viral sequencing results strongly suggest that MERS-CoV originated from bat ancestors after

evolutionary recombination process, primarily in dromedary camels in Africa. The prevalence of MERS-CoV

antibodies, the identification of MERS-CoV RNA and viable virus from dromedary camels of Eastern Africa and

the Arabian Peninsula are the suggestive evidence for inter-transmission of the virus, primarily from camels to

humans and its public health risks. However, the infection in camel is mostly asymptomatic. In contrast to the

camel case, the clinical signs and symptoms of MERS-CoV infection in humans ranges from an asymptomatic

or mild respiratory illness to severe pneumonia and multi-organ failure with an overall mortality rate of about

35%. Though inter-human spread within health care settings is responsible for the majority of reported MERS-

CoV human cases, the virus is currently incapable of causing sustained human-to-human transmission

(pandemic occurrence). Currently, there is no specific drug or vaccine available for treatment and prevention of

MERS-CoV. The important measures to control MERS-CoV spread are strict regulation of camel movement,

regular herd screening and isolation of infected camels, use of personal protective equipment by camel

handlers and awareness creation on the public where consumption of unpasteurized camel milk is common.

Therefore, urgent global epidemiological studies are required, to understand the transmission patterns and the

human cases of MERS-CoV and also for the proper implementation of the above-mentioned control measures.

Keywords: Bats, Dipeptidyl peptidase 4, Dromedary camels, MERS-CoV, SARS-CoV, Transmission

Abbreviations

COV

Coronavirus

MERS-CoV

SARS-CoV

DPP4

WHO

Middle East respiratory syndrome coronavirus

Severe respiratory syndrome corona virus

Dipeptyl peptidase 4

World Health Organization

ICTV

PCR

International Committee on Taxonomy of Virus

Polymerase Chain Reaction

Rt-PCR

Hcov

Real Time Polymerase Chain Reaction

Human Coronaviruses

ORF

Open Reading Frame

CDC

Centers for Disease Control and Prevention

European Centre for Disease Prevention and Control

Enzyme-linked immune sorbent assay

Upstream of the envelope gene

Bat coronaviruses

ECDC

ELISA

UpE

BtCOV

INTRODUCTION

Coronaviruses (CoV) are enveloped, positive-sense RNA viruses with large genomes (29–32 kb) packaged in particles with

corona-like morphology (Lai et al., 2007 ). They can infect humans, as well as a variety of animals, such as bats, mice,

birds, dogs, pigs, and cattle, causing mainly respiratory and enteric diseases (Perlman and Net land, 2009 ).

Citation: Kassahun B, Berhanu T and Damtew B (2020). Review on coronavirus, a middle east respiratory syndrome (MERS-CoV). Online J. Anim. Feed Res., 10(1): 01-

11. www.ojafr.ir

Before the 21st century, it was believed that human corona viruses, represented by the virus‘s hCoV-OC43 and hCoV-

229E, can only cause mild respiratory symptoms (Saif, 2004 ). This notion changed after the outbreak of the severe acute

respiratory syndrome (SARS) in 2002-2003, when a previously unknown human corona virus, named severe acute

respiratory syndrome corona virus (SARS-CoV), caused the first corona virus-associated human epidemic, infecting

approximately 8000 and killing 774 people (Peiris et al., 2004 ). In the years that followed, two additional human corona

viruses were discovered, namely hCoV-NL63 and hCoV-HKU1 (Woo et al., 2005 ). All known human corona viruses are

believed to have a zoonotic origin, with bats playing a major role in the interspecies transmission (To et al., 013 ).

MERS-CoV is the second newly discovered Beta corona virus lineage 2C and initially recognized in the Kingdom of

Saudi Arabia in June 2012, when an elderly Saudi Arabian man was admitted to a local hospital with acute pneumonia

and later died of progressive severe respiratory illness and renal failure (Zaki et al., 2012 ). The World Health Organization

(WHO) global case count for MERS was 1952 laboratory-confirmed cases, including at least 693 deaths (case fatality rate

36%) from September 2012 to 3 April 2017 (WHO, 2017 ).

MER-CoV previously called human corona virus-Erasmus Medical Center was discovered by Zaki et al. (2012) in

Saudi Arabia in 2012. In May 2013, the Corona Virus Study Group of the International Committee on Taxonomy of Viruses

renamed the virus ―Middle East respiratory syndrome corona virus (Murphy et al., 2012; Degroot, 2013 ). MERS-CoV marks

the second known zoonotic introduction of a highly pathogenic corona virus, probably originating from bats (Sharif and

Kanj, 2014 ). Three lines of evidence currently support this theory: Firstly, the very close phylogenetic similarity with the bat

Beta corona viruses: BtCoV-HKU4 and BtCoV-HKU5 (Van bohemeen et al., 2012 ). Secondly closely related corona virus

sequences have been recovered from bats in Africa, Asia, the Americas, and Eurasia; and thirdly MERS-CoV uses the

evolutionary conserved dipeptidylpeptidase 4 (DPP4) protein in Pipistrellus pipistrellus bats for cell entry (Raj et al.,

2013 ).

Since human-bat contact is limited, camels have been implicated as probable intermediate hosts. MERS-CoV

appears to have been circulating in dromedary camels for over 20 years (Corman et al., 2014 ). Many studies have now

identified dromedary camels (Camelus dromedarius) as a natural host for MERS-CoV, and there appears to be ample

evidence of wide spread infection in dromedaries in the Middle East and in many parts of Africa (Reusken et al., 2014a,

Hamid et al., 2015 ). MERS-CoV strains isolated from dromedaries are genetically and phenotypically very similar or

identical to those infecting humans (Farag et al., 2015 ).

While corona viruses affect wide animal species (Woo et al., 2012a ), MERS-CoV have affects limited host ranges. In

the last few years, a large spectrum of domestic species has been negative after MERS-CoV serology tests, including

horses, cattle, water buffalo, chickens, goats, and Bactrian camels (hemida et al., 2013 ). An exception was published

recently when antibodies were detected in Alpaca (Vicugna pacos) in Qatar (Reusken et al., 2016 ) and susceptibility of

pigs and llamas to MERS-CoV infection (Vergera et al., 2017 ).

In the case of MERS-CoV transmission, there is a large uncertainty about the various exposure pathways associated

with new dromedary camel or human cases, and, although published research on MERS-CoV is actively increasing (Zy oud

et al., 2016 ), few transmission risks have yet been quantified.

Therefore, the objective of this paper was to review the public health risk and transmission of Middle East

Respiratory Syndrome.

ETIOLOGY AND TAXONOMY

Middle East respiratory syndrome (MERS), an emerging infectious disease, is caused by the MERS-corona virus (MERS-

CoV) (Zaki et al., 2012 ). CoVs taxonomically belong to the subfamily Coronavirine, family Coronaviridae, in the order

Nidoviales, and can be further classified into four genera: Alpha corona virus, Beta-corona virus, Gamma corona virus and

Delta corona virus (De Groot, 2011 ).

The genus Beta corona virus contains four different lineages, A, B, C and D. The human corona virus‘s hCoV-229 and

hCoV-NL63 belong to the genus Alpha corona virus, while hCoV-OC43 and hCoV-HKU1 belong to the lineage A of the genus

Beta corona virus. SARS-CoV belongs to the genus Beta corona virus of lineage B while MERS-CoV grouped under lineage c

beta corona virus. The genera Gamma and Delta corona virus contain only viruses that infect animals (ICTV, 2012 ).

Phylogenetic analysis performed by Zaki et al . (2012) after the isolation of MERS-CoV from the Saudi patient

suggested that the virus belongs to the lineage C of the genus Beta coronavirus, together with the bat coronaviruses

BtCoV-HKU4 and BtCoV-HKU5, which have been isolated from the species Tylony cterispachypus and Pipistrellus abramus,

respectively (Woo et al., 2012a ).

As stated by the ICTV, viruses that present greater than 90% sequence identity in their replicase domains belong to

the same species. To investigate whether the newly identified virus is the prototype of a novel virus species, the amino

acid sequence of the replicase gene obtained by sequencing of the PCR fragments that the pan-coronavirus PCR yielded

was aligned with the respective sequences of its closest relatives, BtCoV-HKU4 and BtCoV-HKU5 (ICTV, 2012 ).

The comparison showed that the identity the viruses shared was greater than 80%, suggesting that the discovered

virus represents a novel Beta corona virus species, the first human coronavirus described in lineage C of this genus. These

results were repeated by the study of Van Boheemen et al. (2012), after they obtained the complete genome sequence of

the the virus.

Citation: Kassahun B, Berhanu T and Damtew B (2020). Review on coronavirus, a middle east respiratory syndrome (MERS-CoV). Online J. Anim. Feed Res., 10(1): 01-

11. www.ojafr.ir

EPIDEMIOLOGY OF THE DISEASE

Geographic distribution

According to WHO report, MERS cases reported from 27 countries including Arabian peninsula (Jordan, Kuwait,

Lebanon, Oman, Qatar, Saudi Arabia, the United Arab Emirates, Iran, Yemen), Europe (Austria, France, Germany, Greece,

Italy, Netherland Turkey and UK), Asia (China, Philippines, Malaysia, Thailand, Republic of Korea), Africa (Algeria, Egypt,

Tunisia) and USA. In the European and Asian countries as well as in Algeria, Egypt, Tunisia, and the United States, patients

developed illness after returning from the Arabian Peninsula (WHO, 2019 ). In the United Kingdom, France, Italy, and

Tunisia, limited human-to-human transmission occurred among close contacts of the index cases (WHO, 2015 ). MERS

outbreak is ongoing in South Korea since May 2015; the index case was a man who had traveled to Bahrain, the United

Arab Emirates, Saudi Arabia, and Qatar. All of the cases outside of the Middle East have had a direct or indirect

connection to the Middle East.

Figure 1 - Map showing confirmed global cases of MERS-CoV. Source: WHO (2017).

Virus replication on cyclophilin A

CypA is one of the most abundant cytosolic proteins constituting 0.1–0.4% of the total cellular protein content

(Harding et al., 1986 ). Data from different labs suggest that relatively low levels of CypA may suﬃce to support eﬃcient

coronavirus replication. Cyclophilins were initially implicated as host factors in coronavirus replication during studies with

general Cyp inhibitors such as cyclosporine A (CsA). In cell culture, the replication of a variety of coronaviruses was found

to be strongly inhibited by low micromolar concentrations of cyclosporine A and the non-immunosuppressive Cs A analogs

Alisporivir. The cyclosporine A dependence of the replication corona viruses in the same cell line (Huh7), in which CypA

expression was knocked-out using CRISPR/Cas9 gene editing technology (de wilde et al , 2017 ).

Reservoirs and host susceptibility

Dipeptidyl peptidase 4 (DPP4; also, known as CD26) has been identified as the receptor for the MERS-CoV spike

protein and is required for viral binding and entry into host cells (Raj et al., 2013 ). DPP4 is a type II Transmembrane

glycoprotein that is expressed on epithelial and endothelial cells throughout the body (Lambeir et al., 2003 ). Although

DPP4 is evolutionarily conserved, differences in the amino acids present in its extracellular domain, which interacts with

MERS-CoV spike protein, have been noted among various animal species and humans. Specifically, 14 amino acids in

DPP4 appear to be critical in determining whether the MERS-CoV spike protein can bind to DPP4 (Wang et al., 2013 ).

Bats

Bats are known natural reservoirs for several emerging viral infections in humans including rabies, Nipah virus,

Hendra virus and Ebola virus (Han et al., 2015). Several features enable bats to be efficient sources of emerging human

viral infections. As an extremely diverse species with a long evolutionary history, bats have co-evolved with a variety of

viruses. Their lack of B-cell-mediated immune responses allows them to carry viruses without showing overt signs of

illness (Brook and Dobson, 2015 ). Low metabolic rate and suppressed immune response during bats‘ hibernation result in

delayed viral clearance (George et al., 2011 ). Bats live closely together in extremely large numbers facilitating stable

circulation of viruses amongst them (Calisher et al., 2008 ).

Citation: Kassahun B, Berhanu T and Damtew B (2020). Review on coronavirus, a middle east respiratory syndrome (MERS-CoV). Online J. Anim. Feed Res., 10(1): 01-

11. www.ojafr.ir

Furthermore, bats are capable of flying and hence carrying potentially infectious pathogens over considerable

distances (Drexler et al., 2014 ). A pertinent feature of bats is that they chew fruits to absorb their sugars and spit out the

remains. The discarded fruits can be contaminated with viruses from the oral cavity, urine and feces providing a ready

source for transmission to other potential hosts such animals and humans (Brook and Dobson, 2015 ).

Bats have been implicated as the main reservoir of members of the genera Alpha corona virus and Beta corona virus

(Woo et al., 2012b) and play pivotal roles in interspecies transmission of CoVs. This is best exemplified by SARS-CoV,

which was shown to originate from Chinese horseshoe bats (Lau et al., 2005 ), and was probably transmitted directly to

humans (Ge et al., 2013) or through an intermediate host, such as the palm civet (Guan et al., 2004 ). MERS-CoV, together

with bat CoV-HKU4 and HKU5, phylogenetically belongs to lineage C in the genus Beta corona virus (Van Boheemen et al.,

2012 ). Thus, it is suspected that the emerging MERS-CoV might also originate from bats.

A large screening study for beta corona viruses was conducted on fecal specimens taken from 4758 bats of ten

different species in Ghana, and 272 Pipistrellus bats from four European countries showed that a bat derived corona virus

that has a very close phylogenetic relationship to MERS-CoV (Annan et al., 2013 ).

A report from South Africa and Saudi Arabia identified a bat derived corona virus that has a very close phylogenetic

relationship to MERS-CoV (Ithete et al., 2013; Memish et al., 2013c ). An experimental study conducted on Jamaican fruit

bat (Artibeusja maicensis) showed evidence of infection as they shed the virus from their respiratory and intestinal tract

(Munster et al., 2014 ). Therefore MERS-CoV, like many other coronaviruses, originated in bats. This is based on the

isolation of other lineage C beta-corona viruses that are very closely related to MERS-CoV on phylogenetic analysis (De

Benedicts et al., 2014 ).

Dromedary camels

The close phylogenetic relationship of human MERS-CoV isolates with those obtained from bats initially suggested

that MERS-CoV might have originated from bats. However, bats were unlikely to be the direct source of the MERS

outbreak, since MERS cases were rarely found to have a history of contact with bats. Therefore, other animals were

searched as direct sources of zoonotic transmission of MERS-CoV (Han et al., 2016 ). Multiple lines of evidence implicate

dromedary camels in the emergence and transmission of MERS CoV.

MERS-CoV antibodies are highly prevalent in dromedary camels from across the Arabian Peninsula, North Africa and

Eastern Africa (Nowotny and Kolodziejek, 2014 ). The high prevalence of MERS-CoV seropositivity in Africa and the Middle

East suggests that animal movement has facilitated the transmission and circulation of MERS-CoV amongst dromedary

camels in these regions. MERS-CoV antibodies have neither been found in Mongolian or Dutch Bactrian camels nor in

South American camelids such as ilamas, alpacas and guanacos (Reusken et al., 2013a ).

MERS-CoV reported by RT-PCR in oro-nasal and faecal samples from dromedary camels in multiple locations in the

Arabian Peninsula (Hemida et al., 2013 ). The four of 110 dromedary camels in which MERS-CoV RNA was detected in

Egypt were all imported from Sudan or Ethiopia for slaughter (Chu et al., 2014 ). MERS-CoV was also detected by RT-PCR

in symptomatic camels. Dromedaries with active MERS-CoV infection exhibited symptoms such muco-purulent nasal and

lachrymal discharge, cough, sneezing, fever and loss of appetite (Memish et al., 2013b ).

The potential infectiousness of MERS-CoV recovered from dromedary camels was evident its capability to cause ex-

vivo infection in human respiratory cells and human hepatoma cells. Successful MERS-CoV cultures usually coincide with

corresponding high viral loads in the same specimens (Chan et al., 2014 ). Experimental MERS-CoV infection of dromedary

camels with result mild clinical infection manifesting as fever and rhinorhea also implicate dromedary camels in the

emergence and transmission of MERS CoV (Adney et al., 2014a,b ).

Other animal species

Differences in virus susceptibility and pathogenicity between animals of different species could be explained by a

distinct tissue distribution of DPP4, the MERS-CoV receptor. Species with few or no differences in the 14 amino acids

seem to be susceptible to MERS-CoV, including rhesus macaques, common marmosets and result cytopathic cellular

changes and mild to severe respiratory illness (Munster et al., 2013; Falzarano et al., 2014 ). Macaques and marmosets

have already proved useful animal models for the investigation of MERS-CoV (Eckerle et al., 2014 ).

Dromedary camels seems to be the only domestic animal reservoir for MERS-CoV until a recent study by Reusken et

al. (2016) and Vergera et al. (2017 ). Reusken et al. (2016) investigated the MERS-CoV infection status of 15 healthy

alpacas (Vicugnapacos) in a herd of 20 that shared a barn complex with dromedaries. All tested alpacas were seropositive

to MERS-CoV.

Recent study on livestock susceptibility conducted in 2017 indicate that pigs and llamas are susceptible to MERS-

CoV infection (Vergera et al., 2017 ), but the level of MERS-CoV excreted in the nose of dromedaries seems to be much

higher than that of other animal species described so far (Adney et al., 2014a,b ). On the other hands the study showed

that sheep did not show clinical sign. These results are in concordance with those reported by Adney et al. (2016) that

MERS-CoV experimentally inoculated sheep showed no clinical disease and that only small amounts of virus were

detected in nasal swab samples. Even though the receptor binding domain, and in particular key amino acids on the

docking site are identical in horses and human (Van Doremalen et al., 2014 ), horses were not susceptible to MERS-CoV

(Vergera et al., 2017 ). Screening study on equids including horses, donkeys and mules from UAE and Spain result in sero-

Citation: Kassahun B, Berhanu T and Damtew B (2020). Review on coronavirus, a middle east respiratory syndrome (MERS-CoV). Online J. Anim. Feed Res., 10(1): 01-

11. www.ojafr.ir

negative for MERS-CoV (Meyer et al., 2015 ). These results highlight that other mechanisms, such as epithelial cell

permissibility or strong innate immune responses, may inﬂuence the establishment of infection. Differences in the

number of goblet cells in the lining epithelium and mucus covering epithelial surfaces, which may have impeded the

binding of the virus to the respiratory epithelium of horses (Vergera et al., 2017 ). Serological study, conducted in Saudi

Arabia and Europe from sheep, goats, cattle, and chickens representing different geographical areas within the country

were resulted sero negative for MERS-CoV (Hemida et al., 2013; Reusken et al., 2013a ). In addition ferrets, hamsters, and

mice are resistant to infection (Van et al., 2014 ).

Source of infection and transmission

There is growing evidences that the dromedary camel is host species for MERS-CoV and plays an important role in

the transmission of the viruses to human (Azhar et al., 2014 ). In August 2013, for the first time, dromedary camels were

implicated as a possible source of virus causing human infection because of the presences of MERS-CoV specific

neutralizing antibodies in dromedary camels from Oman and other countries in the Arabian Peninsula and North Africa.

An analysis of an outbreak of MERS-CoV infection in humans in Qatar in October 2013 found that dromedary camels

and humans were infected with a nearly identical strain of MERS-CoV (Hemida et al., 2013 ). Widespread circulation of

different genetic variants of MERS-CoV has been found in camels and the presence of MERS-CoV specific antibodies in

samples taken from camels, years earlier. Although dromedary camels are suspected to be the primary source of MERS-

CoV leading to human infections, the true routes of zoonotic transmission remain to be determined (Azhar et al., 2014 ).

Chu et al. (2014) reported that Middle East respiratory syndrome corona virus from Egypt has been fully genetically

sequenced and biologically characterized. While this virus was genetically diverse from viruses causing zoonotic infections

in the Arabian Peninsula, the receptor binding domain of the Egyptian viruses is conserved, indicating that these viruses

would be able to infect the human respiratory tract. This contention is supported by the finding that tropism and virus

replication competence of MERS-CoV from Egypt in ex vivo cultures of the human bronchial and lung is comparable to that

of camel of human virus isolates in the Arabian Peninsula (Chu et al., 2014 ).

Camel to human transmission

Whole MERS-CoV genome sequences obtained from viral cultures of the human and camel isolates were 100%

identical. Importantly, 4-fold rise in MERS-CoV antibody titres was documented in the camels, indicating that active MERS-

CoV infection was probably circulating in the dromedary herd. Later, rising MERS-CoV antibodies were documented in the

patient, suggesting that MERS-CoV infection was transmitted from the camels to the human and not vice versa (Azhar et

al., 2014 ). MERS-CoV was detected in eight asymptomatic dromedary camels at entry into UAE from Oman. Two

asymptomatic men, aged 29 and 33 years, who were in contact with the camels, were found to be positive for MERS-CoV

RNA in their respiratory samples. Partial sequences of MERS-CoV spike and nucleocapsid regions from the human and

linked camels were identical. Within 4–8 days from diagnosis, both patients had undetectable MERS-CoV RNA (Al

Hammadi et al., 2015 ).

MERS-CoV sequences have been detected more commonly in nasal swabs than in rectal specimens of camels

(Hemida et al., 2014 ). Infection of camels in the laboratory also confirmed susceptibility, with a large quantity of virus

shedding from the upper respiratory tract (Adney et al., 2014a,b ). Therefore, droplet transmission or direct contact with

infected camels may be the most likely mode of camel-to-human transmission of MERS-CoV. Direct contact with camels

can only explain some of the primary cases, since some MERS cases did not report any direct contact with camels (Han et

al., 2016 ).

Other possible routes for camel-to-human transmission include food-borne transmission through consumption of

unpasteurized camel milk, raw meat and the camel urine. Camels are an important source of milk in some Middle East

countries and parts of Africa, and more than half of the camel milk is sold as unpasteurized fresh or fermented milk to

local and urban consumers in Saudi Arabia (Faye et al., 2014 ). A survey found the presence of MERS-CoV RNA in the milk

of camels actively shedding the virus (Reusken et al., 2014b ).

An experimental study of the stability of MERS-CoV in milk showed that viable viruses could still be recovered after

48 h regardless of reduction in virus titre, indicating that infection could happen by consumption of unpasteurized fresh

raw milk (Van Doremalen et al., 2014 ). Consumption of undercooked meat from infected camels and handling of infected

raw camel meat without proper protective equipment may also pose risks for getting MERS CoV from camel. An oral–

faecal transmission mode was also suspected. Using protein intrinsic disorder prediction, MERS-CoV was placed into

disorder group C and was likely to persist in the environment for a rather long period of time, and showed high oral–faecal

transmission chances (Goh et al ., 2013 ).

The single study, by Van Doremalen et al. (2013), on Plastic or steel surfaces inoculated with MERS-CoV at different

temperature and relative humidity (RH) shows that the virus remained viable for 24 h. The study reported that MERS-CoV

was more stable under low-temperature/low-humidity conditions, suggesting the potential for MERS-CoV to be

transmitted via contact or fomite transmission due to prolonged environmental presence. By comparison, a well-known

and efficiently transmitted respiratory virus, influenza A virus, could not be recovered in culture beyond four hours under

any conditions. Aerosol experiments found MERS-CoV viability only decreased 7% at low relative humidity at 20 °C. In

comparison, influenza A virus decreased by 95 % (Van Doremalen et al., 2013 ).

Citation: Kassahun B, Berhanu T and Damtew B (2020). Review on coronavirus, a middle east respiratory syndrome (MERS-CoV). Online J. Anim. Feed Res., 10(1): 01-

11. www.ojafr.ir

Enter-human transmission

While the introduction of MERS-CoV to the human species from an animal reservoir seems to be the reason for the

initial infections, the occurrence of clusters suggests that the virus hasadapted to human-to-human transmission. Person-

to-person transmission of MERS-CoV has been documented in several human clusters associated with healthcare

facilities, households and workplace (Assiri et al., 2013a; Memish et al., 2013a ).

Nosocomial outbreak is a distinct hallmark in MERS-CoV transmission involving hospitalized patients, healthcare

workers and close family contacts in healthcare facilities in affected countries in the Middle East and in some countries

where the disease had been exported to, the most recent being the Republic of Korea (RoK). Droplet spread between

humans is considered the mechanism of human-to-human transmission and the need for droplet precautions was

emphasized after the Al-Ahsa hospital, the KSA (Khalafalla et al., 2015 ) and the South Korean outbreaks (Assiri et al.,

2013a ).

MERS-CoV‘s ability to remain viable over long time periods gives it the capacity to thoroughly contaminate a room‘s

surfaces when occupied by an infected and symptomatic patient (Van Doremalen et al., 2013 ). Whether MERS-CoV can

remain a drift and infectious for extended periods (truly airborne) remains unknown. Such findings expand our

understanding of the possibilities for droplets to transmit respiratory viruses in many settings, including hospital waiting

rooms, emergency departments, treatment rooms, open intensive care facilities and private patient rooms. The nature

and quality of air exchange, circulation and filtration are important variables in risk measurement and reduction as is the

use of negative pressure rooms to contain known cases (Assiri et al., 2013a ).

Furthermore, given the high concentration of the virus in the lower respiratory tract of infected patients, airway

suctions or use of bronchoscopes could also serve as a source of transmission (Guberina, 2014 ). The infectiousness of

urine and stool is currently under investigation, since the virus has been detected in urine and stool samples of patients

and based on the fact that cluster patients had been sharing toilet rooms during hospitalization. Transmission via blood

should also be considered a possible route, since scientists claim that the virus might be present in blood (Guery, 2013 ).

This could be correlated to the reported person-to-person transmission in hem dialysis units of a hospital in Saudi Arabia

(Assiri et al., 20 13b ).

Generally, corona viruses are transmitted among humans via aerosol droplets and/or through direct contact with

other secretions (stool, urine etc.) (Danielsson, 2012 ). Currently, the pathways used by MERS-CoV for inter human

transmission remain unknown. Several case investigations have suggested that airborne transmission seems to be the

most likely route (Memish et al., 2013a ).

Figure 2 - Reported Infection sources and transmission routes of MERS-CoV between bats, camels and human (Source:

Omrani et al., 2015).

Public health importance

This novel virus can cause severe acute respiratory disease, mainly in patient with immunosuppressant condition

and underlying disease including diabetes, heart disease, renal failure, hypertension, chronic lung disease, including

asthma and cystic fibrosis. Moreover, history of travel in at risk countries and smoking might have considered as a risk

factors of severe disease (Al Barrak et al., 2012 ). Washing hands, face and hair in camel urine is a traditional custom

among Bedouins and camel-herding peoples in the Arabian Peninsula and East Africa. There are currently no published

data about MERS-CoV in the urine of infected camels, but the virus has been found in low concentration in human urine

samples (Drosten et al., 2013 ), and therefore, consumption of camel urine may represent a risk factor for infection.

Citation: Kassahun B, Berhanu T and Damtew B (2020). Review on coronavirus, a middle east respiratory syndrome (MERS-CoV). Online J. Anim. Feed Res., 10(1): 01-

11. www.ojafr.ir

Dromedary camel meat represents 0.45% of the red meat produced worldwide (Faye, 2013 ). While there is no

evidence of MERS-CoV in camel meat, by analogy with what is known about other viruses like Rift Valley fever virus, we

can assume that the fall in pH of meat with maturation could inactivate the virus (Food and Agriculture Organization) and

that proper cooking would kill the virus. However, handling of raw meat and slaughtering of animals should not be

excluded as a risk factor. The list of at-risk countries, as defined in European Centre for Disease Prevention and Control

(ECDC) rapid risk assessment included Iraq, Israel, Jordan, Qatar, Saudi Arabia, Syria, Kuwait, Lebanon, Palestine, Oman,

UAE, Yemen, Bahrain and Iran (ECDC, 2013 ). People working closely with camels (e.g. farm workers, slaughterhouse

workers and veterinarians) may be at higher risk of MERS-CoV infection than people who do not have regular close

contacts with camels and also health care workers (WHO, 2014 ).

PATHOGENESIS

MERS-CoV pathogenicity is based on the extent pathogen-host interaction. It elicits maximum pathogenic potential

especially in humans. This is due to the fact that MERS-CoV shows a strong tropism for bronchial non-ciliated epithelia.

Furthermore, the virus arrests host bronchial interferon synthesis. It should be noted that most of other viruses causing

respiratory diseases attack and damage epithelial cilia, including Influenza type A.

Molecular studies revealed that cellular receptors for MERS-CoV are exopeptidase (angiotensin converting enzyme

2) (Coleman et al., 2014 ). Moreover, it was found that neutralization of angiotensin converting enzyme 2 by specific

antibodies did not arrest the spread of infection into bronchus and lung alveolus. Extensive investigations showed that

another functional cellular receptor called DDP4 was also involved in the severity of MERS-CoV disease spread into the

lungs (de Wit et al., 2013 ). Of note, receptors for DDP4 are also located in nephrons of kidneys and heart.

During the acute stage of the MERS-CoV infection, there is a severe viremia, leading o spread of MERS-CoV viral

particles in the bloodstream. Hence, MERS-CoV leads not only to the damage of lungs but also kidneys and heart, thereby

resulting in respiratory, renal and cardiac failure, ultimately ending to coma and death (Van Boheemen et al., 2012 ). The

severity is worsened by concurrent secondary bacterial infections. Recent research showed that bacterial infections due to

Staphylococcus aureus, Group A Streptococcus, Streptococcus pneumonia and Haemophilus influenzae type b augment

the pathogenic potential of MERS-CoV, particularly in humans. These bacteria particularly dwell in the oral cavities, tonsils

and pharynx of humans (Lau et al., 2013 ).

CLINICAL FEATURES

The median incubation period of a MERS-CoV infection is 5 days. The clinical manifestations in patients of MERS-CoV

range from subclinical infection to severe respiratory disease. Symptomatic patients often present with fever, myalgia,

and sore throat, shortness of breath, cough, and occasionally hemoptysis. Gastrointestinal symptoms such as diarrhea

and vomiting are also common. Hematological abnormalities reported for clinical cases include thrombocytopenia,

lymphopenia, lymphocytosis, and neutrophilia (Assiriet al., 2013a; Gueryet al., 2013 ). Radiographs with a spectrum of

lower pulmonary infiltrates and consolidation consistent with viral pneumonia (Zakiet al., 2012; Assiriet al., 2013b ).

In contrast to the human cases, camel showed minor clinical signs of the disease, including of rhinorrhea and a mild

increase in body temperature but no other clinical signs were observed (Khalafalla et al., 2013 ) and the nasal discharge

drained from both nostrils varied in character from serous to purulent (Daniella et al., 2014 ). In humans, after the entry of

MERS-CoV viral particles in to lung alveoles, alveolar macrophages fail to contain the spread of infection. The strong host

cellular immune response and cytokine release leads to inflammation and fluid accumulation in lungs.

DIAGNOSIS

Sputum from lower respiratory tract, nasopharyngeal swab, whole blood, tissue from biopsy or autopsy including from

lung and serum for serology are important for virus detection. Lower respiratory tract specimens (such as tracheal

aspirates and Broncho alveolar lavage) appear to have the highest virus titre. Upper respiratory tract specimens are also

recommended, especially when lower respiratory tract specimens cannot be collected (Guery et al., 2013 ).

Rapid verification of cases of novel corona virus infection will be based on detection of unique sequences of viral

RNA by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and immune fluorescence. However,

antibodies against beta corona viruses are identified to cross react within the genus. Therefore, immunofluorescence

effectively limits their use to confirmatory applications (Corman et al., 2012b ). However, for detection of MERS-CoV in

particular, alternative RT-PCR assays are required, detecting certain targets that have been described to be specific for

the virus (Van Boheemen et al., 2012 ).

Corman (2012a) proposed two RT-PCR assays for the detection of the virus, each one targeting different parts of the

viral genome. The first assay targets a region upstream of the envelope (E) gene (upE assay), while the second assay

targets part of ORF1b (ORF1b assay), which does not overlap with the target of pan-coronavirus assay. The upE assay was

found to be more sensitive in comparison to the ORF1b assay. Thus, the use of the upE assay is recommended for

screening, while the ORF1b assay can be used for confirmation (Corman et al., 2012b ).The specificity of both assays was

Citation: Kassahun B, Berhanu T and Damtew B (2020). Review on coronavirus, a middle east respiratory syndrome (MERS-CoV). Online J. Anim. Feed Res., 10(1): 01-

11. www.ojafr.ir

confirmed by excluding cross-reactivity with the other known human corona viruses. A third assay, optimized for

sensitivity, was described by the same group, this time targeting ORF1a. Overall, a combination of the upE and ORF1a

assay seems to be the optimal approach for MERS-CoV detection (Corman et al., 2012a ).

Several serology assays have been developed for the detection of MERS-CoV antibodies, including immuno-

fluorescence assays and a protein microarray assay (Reusken et al., 2013b ). The Center of Disease Control and

Prevention (CDC) has developed a two-stage approach, which uses an enzyme-linked immune sorbent assay (ELISA) for

screening followed by an indirect immunofluorescence test or micro neutralization test for confirmation.

PREVENTION AND CONTROL

Since there are currently no effective drug therapies to treat or prevent the infection, clinical management of patients with

severe disease largely relies on meticulous intensive care support and prevention of complications. This includes

hydration, antipyretic, analgesics, respiratory support, and antibiotics, if needed, for bacterial super infection. Current

treatment is based on previous experience with the Severe Acute Respiratory Syndrome-Coronavirus (SARS-CoV), in vitro

studies, and case series. Various agents have been tried, including those that block virus entry, inhibit viral replication, or

interfere with host immune response (Al-Tawfiq and Memish, 2014 ).

Monoclonal antibodies that efficiently block the interaction between the MERS-CoV envelope spike glycoprotein and

a human protein DDP4 have been developed using a humanized mouse (transgenic mouse). These researchers are now

working to move the antibodies into human trials. Based on experience with SARS-CoV, the use of convalescent plasma,

hyper-immune globulin, or human monoclonal antibodies that contain neutralizing antibodies may be efficacious and is

recommended as first-line treatment when available (Jiang et al., 2014 ).

Understanding the zoonotic sources of MERS-CoV might guide control and prevention of the disease. The WHO

advises people at risk of MERS-CoV infection to avoid contact with camels, to practice good hand hygiene, and to avoid

drinking raw milk or eating contaminated food unless it is properly washed, peeled or cooked (WHO, 2014 ). Since most of

the cases occur in the health care setting, it is thoughtful that all health care workers practice appropriate infection

control measures when taking care of patients with suspected or confirmed MERS-CoV (WHO, 2015 ).Currently, there is no

specific drug or vaccine available for treatment of infection caused by MERS-CoV. Even though, a number of antiviral

medicines are currently under study (Zumla et al., 2015 ), there is no licensed vaccine to prevent MERS-CoV infection.

However, one company has developed an experimental candidate MERS-CoV vaccine (Novavax, 2013 ). 0 also developed

other candidate vaccines which are being studied as full-length infectious DNA clone of the MERS-CoV genome in a

bacterial artificial chromosome.

CONCLUSION

Middle East respiratory syndrome is zoonotic diseases causing severe lower respiratory illness and now considered a

threat to global public health. The current knowledge about virus is limited, since many important epidemiological and

clinical aspects remain unknown. Transmission of MERS-CoV from camel to human is well documented and studied by

different researchers but is generally not very efficient because transmission route of the virus back from human to camel

is still hypothetical.

The exact mechanism of transmission is not clear, including whether other intermediate hosts are involved, which

will be a risk for new incidence of the disease, especially for those countries in which infection cases were not reported.

Although MERS-CoV displays lower transmissibility among humans than SARS-CoV, the possibility that future mutations

will render the virus highly transmittable, with a devastating outcome, cannot be discarded.

In the light of aforementioned conclusions the following general and specific points are recommended.



Urgent epidemiologic investigations through surveillance on environmental, animal and testing around sporadic

unexplained cases are needed to find other animal reservoirs.



Extensive efforts are required to speed up the development of an effective therapy and vaccine.

Camels may play important role in transmission of the virus, and the common practices in pastoral areas of

consuming unpasteurized camels‘ milk and raw meat should be avoided.



Health care workers caring for patients under investigation for MERS-CoV or confirmed cases should exercise

standard precautions including hand hygiene, as well as contact or air borne precautions.

DECLARATION

Corresponding author

E-mail:kassahunberhanu110@gmail.com

Acknowledgement

The authors would wish to acknowledge Haramaya University, college of veterinary medicine staff for their valuable

and constructive comments on preparation of this review.

Citation: Kassahun B, Berhanu T and Damtew B (2020). Review on coronavirus, a middle east respiratory syndrome (MERS-CoV). Online J. Anim. Feed Res., 10(1): 01-

11. www.ojafr.ir

Authors‘ contribution

Dr. Birhanu and Dr. Kassahun participate in design the topic of the review. Dr. Damtew performed by gathering the

data. In addition, Dr. kassahun carefully revised and write the manuscript. Finally, all authors read and approved the final

manuscript.

Availability of data

The data can be availed to the journal upon request.

Conflict of interest

The authors declare they have no competing of interests.

REFERENCES

Adney DR, Brown VR, Porter SM, Bielefeldt OH, Hartwig AE, Bowen RA (2016). Inoculation of goats, sheep, and horses with MERS-CoV does

not result in productive viral shedding. Viruses. 8(8): 230. Google Scholar

Adney DR, van Doremalen N, Brown VR, Bushmaker T, Scott D, de Wit E (2014a).Replication and shedding of MERS-CoV in upper respiratory

tract of inoculated dromedary camels. Emerg Infect Dis. 20:1999–2005. Google Scholar

Adney DR, van Doremalen N, Brown VR, Bushmaker T, Scott D, de Wit E, Bowen RA, Munster VJ (2014b). Replication and shedding of MERS-

CoV in upper respiratory tract of inoculated dromedary camels. Emerging Infectious Diseases. 20(12):1999. Google Scholar

Al Barrak AM, Stephens GM, Hewson R, Memish ZA (20120). Recovery from severe novel coronavirus infection. Saudi Med J. 33 (12):1265-

1269. Google Scholar

Al Hammadi AM, Chu DKW, Eltahir YM, AlHosani F, AlMulla M, Tarnini W (2015). Asymptomatic MERS-CoV infection in humans possibly

linked to infected camels imported from Oman to United Arab Emirates. Emerg Infect Dis. 21(12): 2197-2200. Google Scholar

Almazan F, Marta L, Diego D, Sola I, Zuñiga SA, Jose L, Torres N, Marquez-Jurado S, Andrés G. and Enjuanes L (2013). Engineering a

Replication-Competent, Propagation-Defective Middle East Respiratory Syndrome Coronavirus as a Vaccine Candidate. MBio.4:

e00650-13. Google Scholar

Al-Tawfiq JA, Memish ZA (2014). What Are Our Pharmacotherapeutic Options for MERS-CoV? Expert Review of Clinical Pharmacolog. 7: 235-

238. DOI: https://dx.doi.org/10.1586/17512433.2014.890515 .

Annan A, Baldwin HJ, Corman VM, Klose SM, Owusu M, Nkrumah EE (2013). Human betacoronavirus 2c EMC/2012-related viruses in bats,

Ghana and Europe. Emerg Infect Dis. 19:456. Google Scholar

Assiri A, Al-Tawﬁq J, Al-Rabeeah A (2013b). Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East

Respiratory Syndrome coronavirus disease from Saudi Arabia: a descriptive study. Lancet Infect Dis. 13:752–761. Google Scholar

Assiri A, McGeer A, Perl TM, Price CS, Al Rabeeah AA, Cummings DA (2013a). Hospital outbreak of Middle East respiratory syndrome

coronavirus. N Engl J Med. 369:407–16. Google Scholar

Azhar EI, El-Kafrawy SA, Farraj SA, Hassan AM, Al-Saeed MS, Hashem AM (2014). Evidence for camel-to-human transmission of MERS

coronavirus. N Engl J Med. 370:2499–2505. Google Scholar

Brook CE, Dobson AP (2015). Bats as ‗special‘ reservoirs for emerging zoonotic pathogens. Trends Microb. 23:172–180. Google Scholar

Calisher CH, Childs JE, Field HE, Holmes KV, Schountz T (2008). Bats: Important reservoir hosts of emerging viruses. Clin Microbiol Rev.

19:531–545. Google Scholar

Centers for Disease

Control and Prevention

(CDCP) (2016). Interim guidance

for

healthcare professionals.

http://www.cdc.gov/coronavirus/mers/interim-guidance.html Accessed on April 20, 2017.

Chan RW, Hemida G, Kayali G, Chu DK, Poon LL, Alnaeem A (2014).Tropism and replication of Middle East respiratory syndrome coronavirus

from dromedary camels in the human respiratory tract: an in-vitro and ex-vivo study. Lancet Respir Med. 2:813–822. Google Scholar

Chu DK, Poon LL, Gomaa MM, Shehata MM, Perera RA, Abu Zeid D (2014). MERS coronaviruses in dromedary camels. Egypt. Emerg Infect

Dis. 20:1049–1053. Google Scholar

Coleman CM, Matthews KL, Goicochea L, Frieman MB (2014). Wild-type and innate immune-deficient mice are not susceptible to the Middle

East respiratory syndrome coronavirus. J Gen Virol. 95: 408-412. Google Scholar

Corman VM, Eckerle I, Bleicker T, Zaki A, Landt O, Eschbach-Bludau M, van Boheemen S, Gopa R, Ballhause M, Bestebroer TM, Muth D,

Müller MA, Drexler JF, Zambon M, Osterhaus AD, Fouchier RM, Drosten C (2012a). Detection of a novel human coronavirus by real-

time reverse-transcription polymerase chain reaction. Euro Surveill. 17(40): 20288. Google Scholar

Corman VM, Jores J, Meyer B, Younan M, Liljander A, Said MY, ... & Bornstein S (2014). Antibodies against MERS coronavirus in dromedary

camels, Kenya, 1992–2013. Emerging Infectious Diseases, 20(8), 1319. Google Scholar

Corman VM, Müller MA, Costabel U, Timm J, Binger T, Meyer B, Kreher P, Lattwein E, Eschbach-Bludau M, Nitsche A, Bleicker T, Landt O,

Schweiger B, Drexler JF, Osterhaus AD, Haagmans BL, Dittmer U, Bonin F, Wolff T, Drosten C (2012b). Assays for laboratory

confirmation of novel human coronavirus (hCoV-EMC) infections. Euro Surveill. 17(49): 20334. Google Scholar

Danielsson N, on behalf of the ECDC Internal Response Team, Catchpole M (2012). Novel coronavirus associated with severe respiratory

disease: Case definition and public health measures. Euro Surveill. 17 (39): 20282. Google Scholar

De Benedictis P, Marciano S, Scaravelli D, Priori P, Zecchin B, Capua I (2014). Alpha and lineage C betaCoV infections in Italian bats. Virus

Gen. 48 (2):366–371. Google Scholar

De Groot RJ (2011). Middle East respire tory syndrome coronavirus (MERS-CoV): announcement of the Coronavirus Study Group. J Virol.

87:7790–779. PMC 3700179

de Wilde, Adriaan & Zevenhoven-Dobbe, Jessika & Beugeling, Corrine & Chatterji, Udayan & Jong, Danielle & Gallay, Philippe & Szuhai,

Karoly & Posthuma, Clara & Snijder, Eric. (2017). Coronaviruses and arteriviruses display striking differences in their cyclophilin A-

dependence during replication in cell culture. Virology. 517: 148-156 DOI: https://doi.org/10.1016/j.virol.2017.11.022 . Google

Scholar

de Wit E, Rasmussen AL, Falzarano D, Bushmaker T, Feldmann F, Brining DL, Fischer ER, Martellaro C, Okumura A, Chang J, Scott D,

Benecke AG, Katze MG, Feldmann H, Munster VJ(2013). Middle East respiratory syndrome coronavirus causes transient lower

respiratory tract infection in rhesus macaques. Proc Natl Acad Sci. 110:16598-16603. Google Scholar

Drexler JF, Corman VM, Drosten C (2014). Ecology, evolution and classifcation of bat corona viruses in the aftermath of SARS. Antiviral Res.

101:45–56. Google Scholar

Citation: Kassahun B, Berhanu T and Damtew B (2020). Review on coronavirus, a middle east respiratory syndrome (MERS-CoV). Online J. Anim. Feed Res., 10(1): 01-

11. www.ojafr.ir

Drosten CM, Seilmaier VM, Corman W, Hartmann G, Scheible S, Sack W, Guggemos R, Kallies D, Muth S, Junglen MA, Muller W, Haas H,

Guberina T, Rohnisch M, Schmid-Wendtner S, Aldabbagh U, Dittmer H, Gold P, Graf F, Bonin A, Rambaut CM, Wendtner (2013).

Clinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection. Lancet Infect Dis. 13:

745–751. Google Scholar

Eckerle I, Corman VM, Muller MA, Lenk M, Ulrich RG, Drosten C(2014). Replicative capacity of MERS coronavirus in livestock cell lines.

Emerg Infect Dis.20:276–279. Google Scholar

Europian center for disease prevention and control (ECDC)(2013). Severe respiratory disease associated with a novel coronavirus.

http://www.ecdc.europa.eu/en/publications/20121207-Novel-coronavirusrapidrisk assessment, Assessed on April 10, 2017.

Falzarano D, de Wit E, Feldmann F (2014). Infection with MERS-CoV causes lethal pneumonia in the common marmoset. PLoSPathog.10

(8): 1004250. Google Scholar

Farag EA, Reusken CB, Haagmans BL, Mohran KA, Raj VS, Pas SD (2015). High proportion of MERS-CoV shedding dromedaries at slaughter

house with a potential epidemiological link to human cases. Infect Ecol Epidemiol. 5: 28305. Google Scholar

Faye B, Madani H, El-Rouili S (2014). Camel milk value chain in Northern Saudi Arabia. Emirates J Food Agric. 26:359–365. Google Scholar

Ge XY, Li JL, Yang XL, Chmura AA, Zhu G, Epstein JH(2013). Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2

receptor. Nature. 503:535–538. Google Scholar

George DB, Webb CT, Farnsworth ML, O'Shea TJ, Bowen RA, Smith DL (2011). Host and viral ecology determine bat rabies seasonality and

maintenance. Proc Nat AcadSci USA.108:10208–10213. Google Scholar

Goh GK, Dunker A K, Uversky V (2013). Prediction of intrinsic disorder in MERS-CoV/HCoV-EMC supports a high oral–fecal transmission.

PLoSCurr Outbreaks. Google Scholar

Guan Y, Peiris JSM, Yuen KY (2004). Severe acute respiratory syndrome. Nat Med. 10: S88–97. PMID: 15577937 ; DOI:

https://doi.org/10.1038/nm1143 .

Guberina H, Witzke O, Timm J, Dittmer U, Müller MA, Drosten C, Bonin F (2014). A patient with severe respiratory failure caused by novel

human coronavirus: Case report. Infection. 42(1): 203-6. Google Scholar ; PMID: 23900771 ; DOI: https://doi.org/10.1007/s15010-

013-0509-9 .

Guery B (2013). Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of

nosocomial transmission. The Lancet. 381: 2265–2272. Google Scholar

Han HJ, Wen HL, Zhou CM, Chen FF, Luo LM, Liu JW (2015). Bats as reservoirs of severe emerging infectious diseases. Virus Res. 205:1-6.

Google Scholar

Harding MW, Handschumacher RE, Speicher DW (1986). Isolation and amino acid sequence of cyclophilin. J. Biol. Chem. 261, 8547–8555.

Google Scholar

Hemida MG, Chu DK, Poon LL, Perera RA, Alhammadi MA (2014). MERS coronavirus in dromedary camel herd. Saudi Arabia. Emerg Infect

Dis. 20:1231–1234. Google Scholar

Hemida MG, Perera RA, Wang P, Alhammadi MA, Siu LY, Li M (2013). Middle East respiratory syndrome (MERS) coronavirus seroprevalence

in domestic livestock in Saudi Arabia. Eurosurveillance. 18 (50): 21–7. Google Scholar

http://www.who.int/emergencies/mers-cov/en/], Accessed on May 9, 2017.

Ithete NL, Stoffberg S, Corman VM, Cottontail VM, Richards LR, Schoeman MC(2013). Close relative of human Middle East respiratory

syndrome coronavirus in bat, South Africa. Emerg Infect Dis.19:1697–9. Google Scholar

Jiang L, Wang N, Zuo, T (2014). Potent neutralization of MERS-CoV by human neutralizing monoclonal antibodies to the viral spike

glycoprotein.SciTranslMed.6:234-59. Google Scholar

Khalafalla, A. I., Lu, X., Al-Mubarak, A. I., Dalab, A. H. S., Al-Busadah, K. A., & Erdman, D. D. (2015). MERS-CoV in upper respiratory tract and

lungs of dromedary camels, Saudi Arabia, 2013–2014. Emerging Infectious Diseases, 21(7), 1153. Google Scholar

Lai MMC, Perlman S & Anderson LJ (2007). Coronaviridae. Fields Virol. 1305–1336. [in Japanese] https://ci.nii.ac.jp/naid/10031008269/

Lambeir AM, Durinx C, Scharpe L (2003). Dipeptidyl-peptidase IV from bench to bedside: an update on structural properties, functions, and

clinical aspects of the enzyme DPP IV. Crit Rev Clin Lab Sci.40 (3):209–294. Google Scholar

Lau SK, Lau CC, Chan KH, Li CP, Chen H, Jin DY, Chan JF, Woo PC, Yuen KY (2013). Delayed induction of pro inflammatory cytokines and

suppression of innate antiviral response by the novel Middle East respiratory syndrome coronavirus: implications for pathogenesis and

treatment. J Gen Virol. 94:2679-2690. Google Scholar

Lau SKP, Woo PCY, Li KSM, Huang Y, Tsoi HW, Wong BHL (2005). Severe acute respiratory syndrome coronavirus-like virus in Chinese

horseshoe bats. Proc Natl AcadSci USA.102:14040–14045. Google Scholar

Memish ZA, Cotton M, Meyer B, Watson SJ, Alsahafi AJ, Al- Rabeeah AA (2013b). Human infection with MERS coronavirus after exposure to

infected camels, Saudi Arabia. Emerg Infect Dis. 20:1012–1015. Google Scholar

Memish ZA, Mishra N, Olival KJ, Fagbo SF, Kapoor V, Epstein JH (2013c). Middle East respiratory syndrome coronavirus in bats, Saudi Arabia.

Emerg Infect Dis. 19:1819. Google Scholar

Memish ZA, Zumla AI, Assiri A (2013a). Middle East respiratory syndrome coronavirus infections in health care workers. N Engl J Med.

369:884–886. Google Scholar

Meyer B, García-Bocanegra I, Wernery U, Wernery R, Sieberg A, Müller MA (2015). Serologic assessment of possibility for MERS-CoV infection

in equids. Emerg Infect Dis. 21 (1): 181–2. Google Scholar

Munster VJ, Adney DR, Doremalen NV, Brown VR, Miazgowicz KL, Milne rice S (2014). Replication and shedding of MERSCoV in Jamaican

fruit bats. SciRep. 6: 21878. Google Scholar

Munster VJ, de Wit E, Feldmann H (2013). Pneumonia from human coronavirus in a macaque model. NEngl J Med. 368(16):1560–1562.

Google Scholar

Murphy FA, Fauquet CM, Bishop DH, Ghabrial SA, Jarvis AW, Martelli GP, Mayo MA, Summers MD, editors. (2012). Virus taxonomy:

classification and nomenclature of viruses. Springer Science & Business Media; 2012 Dec 6. Google Scholar

Novavax

(2013). Novavax produces MERS CoV vaccine candidate. http://www.novavax.com/download/releases/2013-

006%20CoronaV%20 FINAL%20PR, Accessed on April 13, 2017.

Nowotny N, Kolodziejek J (2013). Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels, Oman. Euro Surveill. 19:

20781. Google Scholar

Omrani AS, Al-Tawfiq JA, Memish ZA. (2015). Middle East respiratory syndrome coronavirus (MERS-CoV): animal to human interaction.

Pathogens and global health. 109(8):354-62. Google Scholar

Perlman S, Netland J (2009). Coronaviruses post-SARS: update on replication and pathogenesis. Nat RevMicrobiol. 7:439–450. Google

Scholar

Citation: Kassahun B, Berhanu T and Damtew B (2020). Review on coronavirus, a middle east respiratory syndrome (MERS-CoV). Online J. Anim. Feed Res., 10(1): 01-

11. www.ojafr.ir

Raj VS, Mou H, Smits SL, Dekkers DH, Muller MA, Dijkman R (2013). Dipeptidyl peptidase 4 is a functional receptor for the emerging human

coronavirus-EMC. Nature.495:251–254. Google Scholar

Reusken C, Mou H, Godeke GJ (2013b). Specific serology for emerging human coronaviruses by protein microarray. Euro Surveill. 18:20441.

Google Scholar

Reusken CB, Ababneh M, Raj VS, Meyer B, Eljarah A, Abutarbush S (2013a). Middle East Respiratory Syndrome coronavirus (MERS-CoV)

serology in major livestock species in an affected region in Jordan. Euro Surveill. 18(50): 20662. Google Scholar

Reusken CB, Farag EA, Jonges M, Godeke GJ, El-Sayed AM, Pas SD, Raj VS, Mohran KA, Moussa HA(2014b). Middle East respiratory

syndrome coronavirus (MERS-CoV) RNA and neutralising antibodies in milk collected according to local customs from dromedary

camels, Qatar. Euro Surveill.19 (23):20829. Google Scholar

Reusken CB, Messadi L, Feyisa A, Ularamu H, Godeke GJ, Danmarwa A(2014a). Geographic distribution of MERS coronavirus among

dromedary camels of Africa. Emerg Infect Dis J. 20 (8): 1370–4. Google Scholar

Reusken CBEM, Schilp C, Raj VS, De Bruin E, Kohl RHG, Farag EABA (2016). MERS-CoV infection of alpaca in a region where MERS-CoV is

endemic. Emerg Infect Dis. 22(6):1129–31. Google Scholar

Saif LJ (2004). Animal coronaviruses: what can they teach us about the severe acute respiratory syndrome? Int Epizoot. 23:643–660.

Google Scholar

Sharif-Yakan A, Kanj SS (2014). Emergence of MERS-CoV in the Middle respiratory syndrome coronavirus. Jour of Gen Virol. 97:274–280.

Google Scholar

To KKW, Hung IFN, Chan JFW, Yuen K (2013). From SARS coronavirus to novel animal and human coronaviruses. J Thorac Dis.5:103–108.

Google Scholar

Van Bohemeen S, de Graaf M, Lauber C, Bestebroer TM, Raj VS, Zaki AM, Osterhaus AD, Haagmans BL, Gorbalenya AE, Snijder EJ, Fouchier

RA (2012). Genomic characterization of a newly discovered coronavirus associated with acute respiratory distress syndrome in

humans. MBio. 3:00473-12. Google Scholar

Van Doremalen N, Bushmaker T, Munster VJ (2013). Stability of Middle East respiratory syndrome coronavirus (MERS-CoV) under different

environmental conditions. Euro Surveill. 18: 38. Google Scholar

Van Doremalen N, Miazgowicz KL, Milne-Price S (2014). Host species restriction of Middle East respiratory syndrome coronavirus through its

receptor, dipeptidyl peptidase 4.J Virol. 88(16):9220–9232. Google Scholar

Vergera-Alert J, van den Brand JM, Widagdo W, Muñoz M , Raj S, Schipper D, Solanes D, Cordón I, Bensaid A, Haagmans BL, Segalés J

(2017). Livestock Susceptibility to Infection with Middle East Respiratory Syndrome Coronavirus. Emerg Infect Dis. 23(2):232-240.

Google Scholar

Wang N, Shi X, Jiang L (2013).Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4. Cell Res.

23(8):986–993. Google Scholar

Woo P, Lau S, Chu CM (2005). Characterization andcomplete genome sequence of a novel coronavirus, coronavirusHKU1, from patients with

pneumonia. J Virol.79:884–895. Google Scholar

Woo PC, Lau SK, Lam CS, Lau CC, Tsang AK, Lau JH (2012b). Discovery of seven novel mammalian and avian coronaviruses in the genus

deltacoronavirus supports bat coronaviruses as the gene source of alpha coronavirus and beta coronavirus and avian coronaviruses as

the gene source of gamma coronavirus and delta coronavirus. J Virol. 86(7):3995–4008. Google Scholar

Woo PCY, Lau SKP, Li KSM, Tsang AKL, Yuen KY (2012a). Genetic relatedness of the novel human group C betacoronavirusto Tylonycteris

bat coronavirus HKU4 and Pipistrellus bat coronavirus HKU5. Emerg Microbes Infect 1: 35. Google Scholar

World

Health

Organization

(2015).

MERS-CoV

the

Republic

Korea

Glance.

http://www.who.int/csr/disease/coronavirus_infections/mers-laboratory-testing/en/], Accessed on April 17, 2019.

World Health Organization. (2014). Interim surveillance recommendations for human infection with Middle East respiratory syndrome

coronavirus. http://www.who.int/csr/disease/coronavirus_infectionsmers-laboratory testing/en/], Accessed on April 10, 2017.

Google Scholar

World health organization. (2019). Confirmed cases of global MERS-CoV.

Zaki A, van Boheemen S, Bestebroer T, Osterhaus A, Fouchier R(2012). Isolation of a novel coronavirus from a man with pneumonia in Saudi

Arabia. NEngl J Med.367: 1814–1820. Google Scholar

Zumla A, Hui DS, Perlman S (2015). Middle East respiratory syndrome. Lancet. 386: 995-1007. Google Scholar

Zyoud SH (2016). Global research trends of Middle East respiratory syndrome coronavirus. BMC Infect Dis. 16:255. Google Scholar

Citation: Kassahun B, Berhanu T and Damtew B (2020). Review on coronavirus, a middle east respiratory syndrome (MERS-CoV). Online J. Anim. Feed Res., 10(1): 01-

11. www.ojafr.ir