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rapid generation of a mouse model for middle east respiratory syndrome.in this era of continued emergence of zoonotic virus infections, the rapid development of rodent models represents a critical barrier to public health preparedness, including the testing of antivirus therapy and vaccines. the middle east respiratory syndrome coronavirus (mers-cov) was recently identified as the causative agent of a severe pneumonia. given the ability of coronavirus to rapidly adapt to new hosts, a major public health concern is that mers-cov will further adapt to replication in ...201424599590
a decade after sars: strategies for controlling emerging coronaviruses.two novel coronaviruses have emerged in humans in the twenty-first century: severe acute respiratory syndrome coronavirus (sars-cov) and middle east respiratory syndrome coronavirus (mers-cov), both of which cause acute respiratory distress syndrome (ards) and are associated with high mortality rates. there are no clinically approved vaccines or antiviral drugs available for either of these infections; thus, the development of effective therapeutic and preventive strategies that can be readily a ...201324217413
study of viral pathogenesis in humanized mice.many of the viral pathogens that cause infectious diseases in humans have a highly restricted species tropism, making the study of their pathogenesis and the development of clinical therapies difficult. the improvement of humanized mouse models over the past 30 years has greatly facilitated researchers' abilities to study host responses to viral infections in a cost effective and ethical manner. from hiv to hepatotropic viruses to middle east respiratory syndrome coronavirus, humanized mice have ...201525618248
protective efficacy of recombinant modified vaccinia virus ankara delivering middle east respiratory syndrome coronavirus spike glycoprotein.middle east respiratory syndrome coronavirus (mers-cov) causes severe respiratory disease in humans. we tested a recombinant modified vaccinia virus ankara (mva) vaccine expressing full-length mers-cov spike (s) glycoprotein by immunizing balb/c mice with either intramuscular or subcutaneous regimens. in all cases, mva-mers-s induced mers-cov-specific cd8(+) t cells and virus-neutralizing antibodies. vaccinated mice were protected against mers-cov challenge infection after transduction with the ...201526018172
origin, evolution, and genotyping of emergent porcine epidemic diarrhea virus strains in the united states.coronaviruses are known to infect humans and other animals and cause respiratory and gastrointestinal diseases. here we report the emergence of porcine epidemic diarrhea virus (pedv) in the united states and determination of its origin, evolution, and genotypes based on temporal and geographical evidence. histological lesions in small intestine sections of affected pigs and the complete genomic sequences of three emergent strains of pedv isolated from outbreaks in minnesota and iowa were charact ...201324129257
screening of an fda-approved compound library identifies four small-molecule inhibitors of middle east respiratory syndrome coronavirus replication in cell culture.coronaviruses can cause respiratory and enteric disease in a wide variety of human and animal hosts. the 2003 outbreak of severe acute respiratory syndrome (sars) first demonstrated the potentially lethal consequences of zoonotic coronavirus infections in humans. in 2012, a similar previously unknown coronavirus emerged, middle east respiratory syndrome coronavirus (mers-cov), thus far causing over 650 laboratory-confirmed infections, with an unexplained steep rise in the number of cases being r ...201424841269
[molecular diagnosis and phylogenetic analysis of the first mers case in turkey].coronaviruses (cov) are enveloped, spherical, single-stranded positive-sense rna viruses causing mainly respiratory and intestinal infections in animals and humans. until recently five types of human coronaviruses (hcov-oc43, hcov-hku1, hcov-nl63, hcov-229e, sars-cov) have been known, however a novel cov has been identified in 2012 in saudi arabia. this virus, namely mers-cov (middle east respiratory syndrome coronavirus), was classified within coronaviridae family, coronavirinae sub-family, bet ...201526313282
bat origin of human coronaviruses.bats have been recognized as the natural reservoirs of a large variety of viruses. special attention has been paid to bat coronaviruses as the two emerging coronaviruses which have caused unexpected human disease outbreaks in the 21st century, severe acute respiratory syndrome coronavirus (sars-cov) and middle east respiratory syndrome coronavirus (mers-cov), are suggested to be originated from bats. various species of horseshoe bats in china have been found to harbor genetically diverse sars-li ...201526689940
surveillance of bat coronaviruses in kenya identifies relatives of human coronaviruses nl63 and 229e and their recombination history.bats harbor a large diversity of coronaviruses (covs), several of which are related to zoonotic pathogens that cause severe disease in humans. our screening of bat samples collected in kenya from 2007 to 2010 not only detected rna from several novel covs but, more significantly, identified sequences that were closely related to human covs nl63 and 229e, suggesting that these two human viruses originate from bats. we also demonstrated that human cov nl63 is a recombinant between nl63-like viruses ...201728077633
polyphyletic origin of mers coronaviruses and isolation of a novel clade a strain from dromedary camels in the united arab emirates.little is known regarding the molecular epidemiology of middle east respiratory syndrome coronavirus (mers-cov) circulating in dromedaries outside saudi arabia. to address this knowledge gap, we sequenced 10 complete genomes of mers-covs isolated from 2 live and 8 dead dromedaries from different regions in the united arab emirates (uae). phylogenetic analysis revealed one novel clade a strain, the first detected in the uae, and nine clade b strains. strain d998/15 had a distinct phylogenetic pos ...201627999424
epidemiological investigation of middle east respiratory syndrome coronavirus in dromedary camel farms linked with human infection in abu dhabi emirate, united arab emirates.the objective of this research was to investigate the prevalence of middle east respiratory syndrome coronavirus (mers-cov) infection primarily in dromedary camel farms and the relationship of those infections with infections in humans in the emirate of abu dhabi. nasal swabs from 1113 dromedary camels (39 farms) and 34 sheep (1 farm) and sputum samples from 2 mers-cov-infected camel farm owners and 1 mers-cov-infected sheep farm owner were collected. samples from camels and humans underwent rea ...201627357298
risk factors for mers coronavirus infection in dromedary camels in burkina faso, ethiopia, and morocco, 2015.understanding middle east respiratory syndrome coronavirus (mers-cov) transmission in dromedary camels is important, as they consitute a source of zoonotic infection to humans. to identify risk factors for mers-cov infection in camels bred in diverse conditions in burkina faso, ethiopia and morocco, blood samples and nasal swabs were sampled in february-march 2015. a relatively high mers-cov rna rate was detected in ethiopia (up to 15.7%; 95% confidence interval (ci): 8.2-28.0), followed by burk ...201728382915
infection with mers-cov causes lethal pneumonia in the common marmoset.the availability of a robust disease model is essential for the development of countermeasures for middle east respiratory syndrome coronavirus (mers-cov). while a rhesus macaque model of mers-cov has been established, the lack of uniform, severe disease in this model complicates the analysis of countermeasure studies. modeling of the interaction between the mers-cov spike glycoprotein and its receptor dipeptidyl peptidase 4 predicted comparable interaction energies in common marmosets and human ...201425144235
treatment with lopinavir/ritonavir or interferon-β1b improves outcome of mers-cov infection in a nonhuman primate model of common marmoset.middle east respiratory syndrome coronavirus (mers-cov) causes severe disease in human with an overall case-fatality rate of >35%. effective antivirals are crucial for improving the clinical outcome of mers. although a number of repurposed drugs, convalescent-phase plasma, antiviral peptides, and neutralizing antibodies exhibit anti-mers-cov activity in vitro, most are not readily available or have not been evaluated in nonhuman primates. we assessed 3 repurposed drugs with potent in vitro anti- ...201526198719
middle east respiratory syndrome coronavirus (mers-cov) origin and animal reservoir.middle east respiratory syndrome-coronavirus (mers-cov) is a novel coronavirus discovered in 2012 and is responsible for acute respiratory syndrome in humans. though not confirmed yet, multiple surveillance and phylogenetic studies suggest a bat origin. the disease is heavily endemic in dromedary camel populations of east africa and the middle east. it is unclear as to when the virus was introduced to dromedary camels, but data from studies that investigated stored dromedary camel sera and geogr ...201627255185
mers-cov antibodies in humans, africa, 2013-2014.dromedaries in africa and elsewhere carry the middle east respiratory syndrome coronavirus (mers-cov). to search for evidence of autochthonous mers-cov infection in humans, we tested archived serum from livestock handlers in kenya for mers-cov antibodies. serologic evidence of infection was confirmed for 2 persons sampled in 2013 and 2014.201627071076
an acute immune response to middle east respiratory syndrome coronavirus replication contributes to viral pathogenicity.middle east respiratory syndrome coronavirus (mers-cov) was first identified in a human with severe pneumonia in 2012. since then, infections have been detected in >1500 individuals, with disease severity ranging from asymptomatic to severe, fatal pneumonia. to elucidate the pathogenesis of this virus and investigate mechanisms underlying disease severity variation in the absence of autopsy data, a rhesus macaque and common marmoset model of mers-cov disease were analyzed. rhesus macaques develo ...201626724387
differential expression of the middle east respiratory syndrome coronavirus receptor in the upper respiratory tracts of humans and dromedary camels.middle east respiratory syndrome coronavirus (mers-cov) is not efficiently transmitted between humans, but it is highly prevalent in dromedary camels. here we report that the mers-cov receptor--dipeptidyl peptidase 4 (dpp4)--is expressed in the upper respiratory tract epithelium of camels but not in that of humans. lack of dpp4 expression may be the primary cause of limited mers-cov replication in the human upper respiratory tract and hence restrict transmission.201626889022
comparative pathology of rhesus macaque and common marmoset animal models with middle east respiratory syndrome coronavirus.middle east respiratory syndrome (mers), which is caused by a newly discovered coronavirus (cov), has recently emerged. it causes severe viral pneumonia and is associated with a high fatality rate. however, the pathogenesis, comparative pathology and inflammatory cell response of rhesus macaques and common marmosets experimentally infected with mers-cov are unknown. we describe the histopathological, immunohistochemical, and ultrastructural findings from rhesus macaque and common marmoset animal ...201728234937
coronaviruses: emerging and re-emerging pathogens in humans and animals.the severe acute respiratory syndrome coronavirus (sars-cov) and recently emerged middle east respiratory syndrome coronavirus (mers-cov) epidemics have proven the ability of coronaviruses to cross species barrier and emerge rapidly in humans. other coronaviruses such as porcine epidemic diarrhea virus (pedv) are also known to cause major disease epidemics in animals with huge economic loss. this special issue in virology journal aims to highlight the advances and key discoveries in the animal o ...201526690088
middle east respiratory syndrome coronavirus spike protein delivered by modified vaccinia virus ankara efficiently induces virus-neutralizing antibodies.middle east respiratory syndrome coronavirus (mers-cov) has recently emerged as a causative agent of severe respiratory disease in humans. here, we constructed recombinant modified vaccinia virus ankara (mva) expressing full-length mers-cov spike (s) protein (mva-mers-s). the genetic stability and growth characteristics of mva-mers-s make it a suitable candidate vaccine for clinical testing. vaccinated mice produced high levels of serum antibodies neutralizing mers-cov. thus, mva-mers-s may serv ...201323986586
vaccines against middle east respiratory syndrome coronavirus for humans and camels.middle east respiratory syndrome coronavirus (mers-cov) is caused by a novel betacoronavirus that was isolated in late 2012 in saudi arabia. the viral infections have been reported in more than 1700 humans, ranging from asymptomatic or mild cases to severe pneumonia with a mortality rate of 40%. it is well documented now that dromedary camels contract the infection and shed the virus without notable symptoms, and such animals had been infected by at least the early 1980s. the mechanism of camel ...201727786402
lack of middle east respiratory syndrome coronavirus transmission from infected camels.to determine risk for middle east respiratory syndrome coronavirus transmission from camels to humans, we tested serum from 191 persons with various levels of exposure to an infected dromedary herd. we found no serologic evidence of human infection, suggesting that zoonotic transmission of this virus from dromedaries is rare.201525811546
hepatitis e: a disease of reemerging importance.hepatitis e virus (hev) is the most common cause of acute viral hepatitis worldwide. originally considered to be restricted to humans, it is now clear that hev and hev-like viruses have several animal reservoirs with complex ecology and genetic diversity, as exemplified by the recent discovery of hev in dromedaries, a previously underestimated reservoir of zoonotic viruses prior to the emergence of middle east respiratory syndrome coronavirus. zoonotic foodborne transmission from pigs and feral ...201525773541
one-health: a safe, efficient, dual-use vaccine for humans and animals against middle east respiratory syndrome coronavirus and rabies virus.middle east respiratory syndrome coronavirus (mers-cov) emerged in 2012 and is a highly pathogenic respiratory virus. there are no treatment options against mers-cov for humans or animals, and there are no large-scale clinical trials for therapies against mers-cov. to address this need, we developed an inactivated rabies virus (rabv) that contains the mers-cov spike (s) protein expressed on its surface. our initial recombinant vaccine, bnsp333-s, expresses a full-length wild-type mers-cov s prot ...201727807241
an orthopoxvirus-based vaccine reduces virus excretion after mers-cov infection in dromedary camels.middle east respiratory syndrome coronavirus (mers-cov) infections have led to an ongoing outbreak in humans, which was fueled by multiple zoonotic mers-cov introductions from dromedary camels. in addition to the implementation of hygiene measures to limit further camel-to-human and human-to-human transmissions, vaccine-mediated reduction of mers-cov spread from the animal reservoir may be envisaged. here we show that a modified vaccinia virus ankara (mva) vaccine expressing the mers-cov spike p ...201626678878
middle east respiratory syndrome coronavirus: transmission, virology and therapeutic targeting to aid in outbreak control.middle east respiratory syndrome coronavirus (mers-cov) causes high fever, cough, acute respiratory tract infection and multiorgan dysfunction that may eventually lead to the death of the infected individuals. mers-cov is thought to be transmitted to humans through dromedary camels. the occurrence of the virus was first reported in the middle east and it subsequently spread to several parts of the world. since 2012, about 1368 infections, including ~487 deaths, have been reported worldwide. nota ...201526315600
global research trends of middle east respiratory syndrome coronavirus: a bibliometric analysis.middle east respiratory syndrome coronavirus (mers-cov) is a virus that causes severe viral pneumonia in humans, known to have a high mortality rate and a similarity in clinical symptoms with severe acute respiratory syndrome coronavirus. it was first isolated in kingdom of saudi arabia (ksa) in 2012 and after that, mers-cov exhibited outbreaks in several regions of the world. this study aimed to assess the characteristics of publications involving mers-cov at global level by using a bibliometri ...201627267256
host cell proteases: critical determinants of coronavirus tropism and pathogenesis.coronaviruses are a large group of enveloped, single-stranded positive-sense rna viruses that infect a wide range of avian and mammalian species, including humans. the emergence of deadly human coronaviruses, severe acute respiratory syndrome coronavirus (sars-cov), and middle east respiratory syndrome coronavirus (mers-cov) have bolstered research in these viral and often zoonotic pathogens. while coronavirus cell and tissue tropism, host range, and pathogenesis are initially controlled by inte ...201425445340
geographic distribution of mers coronavirus among dromedary camels, africa.we found serologic evidence for the circulation of middle east respiratory syndrome coronavirus among dromedary camels in nigeria, tunisia, and ethiopia. circulation of the virus among dromedaries across broad areas of africa may indicate that this disease is currently underdiagnosed in humans outside the arabian peninsula.201425062254
detection of the middle east respiratory syndrome coronavirus genome in an air sample originating from a camel barn owned by an infected patient.middle east respiratory syndrome coronavirus (mers-cov) is a novel betacoronavirus that has been circulating in the arabian peninsula since 2012 and causing severe respiratory infections in humans. while bats were suggested to be involved in human mers-cov infections, a direct link between bats and mers-cov is uncertain. on the other hand, serological and virological data suggest dromedary camels as the potential animal reservoirs of mers-cov. recently, we isolated mers-cov from a camel and its ...201425053787
identification of human neutralizing antibodies against mers-cov and their role in virus adaptive evolution.the newly emerging middle east respiratory syndrome coronavirus (mers-cov) causes a severe acute respiratory syndrome-like disease with ∼43% mortality. given the recent detection of virus in dromedary camels, zoonotic transfer of mers-cov to humans is suspected. in addition, little is known about the role of human neutralizing ab (nab) pressure as a driving force in mers-cov adaptive evolution. here, we used a well-characterized nonimmune human ab-phage library and a panning strategy with proteo ...201424778221
replication and shedding of mers-cov in upper respiratory tract of inoculated dromedary camels.in 2012, a novel coronavirus associated with severe respiratory disease in humans emerged in the middle east. epidemiologic investigations identified dromedary camels as the likely source of zoonotic transmission of middle east respiratory syndrome coronavirus (mers-cov). here we provide experimental support for camels as a reservoir for mers-cov. we inoculated 3 adult camels with a human isolate of mers-cov and a transient, primarily upper respiratory tract infection developed in each of the 3 ...025418529
a highly immunogenic and protective middle east respiratory syndrome coronavirus vaccine based on a recombinant measles virus vaccine platform.in 2012, the first cases of infection with the middle east respiratory syndrome coronavirus (mers-cov) were identified. since then, more than 1,000 cases of mers-cov infection have been confirmed; infection is typically associated with considerable morbidity and, in approximately 30% of cases, mortality. currently, there is no protective vaccine available. replication-competent recombinant measles virus (mv) expressing foreign antigens constitutes a promising tool to induce protective immunity a ...201526355094
mers-cov at the animal-human interface: inputs on exposure pathways from an expert-opinion elicitation.nearly 4 years after the first report of the emergence of middle-east respiratory syndrome coronavirus (mers-cov) and nearly 1800 human cases later, the ecology of mers-cov, its epidemiology, and more than risk factors of mers-cov transmission between camels are poorly understood. knowledge about the pathways and mechanisms of transmission from animals to humans is limited; as of yet, transmission risks have not been quantified. moreover the divergent sanitary situations and exposures to animals ...201627761437
inoculation of goats, sheep, and horses with mers-cov does not result in productive viral shedding.the middle east respiratory syndrome coronavirus (mers-cov) was first recognized in 2012 and can cause severe disease in infected humans. dromedary camels are the reservoir for the virus, although, other than nasal discharge, these animals do not display any overt clinical disease. data from in vitro experiments suggest that other livestock such as sheep, goats, and horses might also contribute to viral transmission, although field data has not identified any seropositive animals. in order to un ...201627548203
from sars coronavirus to novel animal and human coronaviruses.in 2003, severe acute respiratory syndrome coronavirus (sars-cov) caused one of the most devastating epidemics known to the developed world. there were two important lessons from this epidemic. firstly, coronaviruses, in addition to influenza viruses, can cause severe and rapidly spreading human infections. secondly, bats can serve as the origin and natural animal reservoir of deadly human viruses. since then, researchers around the world, especially those in asia where sars-cov was first identi ...201323977429
middle east respiratory syndrome coronavirus: review of the current situation in the world.this article reviews the current epidemiology and clinical presentation of middle east respiratory syndrome coronavirus (mers-cov) infection and describes the preparedness plan of several countries. the mers-cov was first reported in 2012 and has since infected more than 1600 patients in 26 countries, mostly in saudi arabia and the middle east. the epidemiology of the infection is compatible with multiple introductions of the virus into humans from an animal reservoir, probably dromedary camels. ...201628265443
serologic evidence for mers-cov infection in dromedary camels, punjab, pakistan, 2012-2015.dromedary camels from africa and arabia are an established source for zoonotic middle east respiratory syndrome coronavirus (mers-cov) infection among humans. in pakistan, we found specific neutralizing antibodies in samples from 39.5% of 565 dromedaries, documenting significant expansion of the enzootic range of mers-cov to asia.201728221127
outbreak of middle east respiratory syndrome coronavirus in saudi arabia: a retrospective study.the middle east respiratory syndrome (mers) is proposed to be a zoonotic disease. dromedary camels have been implicated due to reports that some confirmed cases were exposed to camels. risk factors for mers coronavirus (mers-cov) infections in humans are incompletely understood. this study aimed to describe the demographic characteristics, mortality rate, clinical manifestations and comorbidities with confirmed cases of mers-cov.201728056850
taking forward a 'one health' approach for turning the tide against the middle east respiratory syndrome coronavirus and other zoonotic pathogens with epidemic potential.the appearance of novel pathogens of humans with epidemic potential and high mortality rates have threatened global health security for centuries. over the past few decades new zoonotic infectious diseases of humans caused by pathogens arising from animal reservoirs have included west nile virus, yellow fever virus, ebola virus, nipah virus, lassa fever virus, hanta virus, dengue fever virus, rift valley fever virus, crimean-congo haemorrhagic fever virus, severe acute respiratory syndrome coron ...201627321961
dromedary camels and the transmission of middle east respiratory syndrome coronavirus (mers-cov).middle east respiratory syndrome coronavirus (mers-cov) is an existential threat to global public health. the virus has been repeatedly detected in dromedary camels (camelus dromedarius). adult animals in many countries in the middle east as well as in north and east africa showed high (>90%) seroprevalence to the virus. middle east respiratory syndrome coronavirus isolated from dromedaries is genetically and phenotypically similar to viruses from humans. we summarize current understanding of th ...201726256102
a novel neutralizing monoclonal antibody targeting the n-terminal domain of the mers-cov spike protein.middle east respiratory syndrome coronavirus (mers-cov) has caused fatal infections, some through hospital-acquired transmission, in affected regions since its emergence in 2012. although the virus is not pandemic among humans, it poses a great threat to public health due to its zoonotic origin. thus, both preventative and therapeutic countermeasures are urgently needed. in this study, we discovered a panel of neutralizing monoclonal antibodies (mabs) against mers-cov, which mapped to a wide ran ...201728536429
middle east respiratory syndrome coronavirus "mers-cov": current knowledge gaps.the middle east respiratory syndrome coronavirus (mers-cov) that causes a severe lower respiratory tract infection in humans is now considered a pandemic threat to the gulf region. since its discovery in 2012, mers-cov has reached 23 countries affecting about 1100 people, including a dozen children, and claiming over 400 lives. compared to sars (severe acute respiratory syndrome), mers-cov appears to kill more people (40% versus 10%), more quickly, and is especially more severe in those with pre ...201526002405
serological evidence of coronavirus infections in native hamadryas baboons (papio hamadryas hamadryas) of the kingdom of saudi arabia.the hamadryas baboon (papio hamadryas hamadryas) is the only indigenous species of non-human primates (nhp) found in the kingdom of saudi arabia (ksa). there are no peer-reviewed publications on viral infections of the baboons of ksa. apart from camels, other animals are likely sources of the novel middle east respiratory syndrome coronavirus (merscov) for humans. we investigated evidence of highly pathogenic coronavirus infections including merscov in a large group of commensal baboons accompan ...201728478775
human neutralizing monoclonal antibody efficiently inhibits mers-cov replication in common marmoset.middle east respiratory syndrome coronavirus (mers-cov) infection in humans is highly lethal, with a fatality rate of 35%. new prophylactic and therapeutic strategies to combat human infections are urgently needed. we isolated a fully human neutralizing antibody, mca1, from a human survivor. the antibody recognizes the receptor-binding domain of mers-cov s glycoprotein and interferes with the interaction between viral s and the human cellular receptor human dipeptidyl peptidase 4 (dpp4). to our ...201728472421
tissue distribution of the mers-coronavirus receptor in bats.middle east respiratory syndrome coronavirus (mers-cov) has been shown to infect both humans and dromedary camels using dipeptidyl peptidase-4 (dpp4) as its receptor. the distribution of dpp4 in the respiratory tract tissues of humans and camels reflects mers-cov tropism. apart from dromedary camels, insectivorous bats are suggested as another natural reservoir for mers-like-covs. in order to gain insight on the tropism of these viruses in bats, we studied the dpp4 distribution in the respirator ...201728446791
no serologic evidence of middle east respiratory syndrome coronavirus infection among camel farmers exposed to highly seropositive camel herds: a household linked study, kenya, 2013.abstracthigh seroprevalence of middle east respiratory syndrome coronavirus (mers-cov) among camels has been reported in kenya and other countries in africa. to date, the only report of mers-cov seropositivity among humans in kenya is of two livestock keepers with no known contact with camels. we assessed whether persons exposed to seropositive camels at household level had serological evidence of infection. in 2013, 760 human and 879 camel sera were collected from 275 and 85 households respecti ...201728719257
searching for animal models and potential target species for emerging pathogens: experience gained from middle east respiratory syndrome (mers) coronavirus.emerging and re-emerging pathogens represent a substantial threat to public health, as demonstrated with numerous outbreaks over the past years, including the 2013-2016 outbreak of ebola virus in western africa. coronaviruses are also a threat for humans, as evidenced in 2002/2003 with infection by the severe acute respiratory syndrome coronavirus (sars-cov), which caused more than 8000 human infections with 10% fatality rate in 37 countries. ten years later, a novel human coronavirus (middle ea ...201728616501
mers-coronavirus: from discovery to intervention.middle east respiratory syndrome coronavirus (mers-cov) still causes outbreaks despite public awareness and implementation of health care measures, such as rapid viral diagnosis and patient quarantine. here we describe the current epidemiological picture of mers-cov, focusing on humans and animals affected by this virus and propose specific intervention strategies that would be appropriate to control mers-cov. one-third of mers-cov patients develop severe lower respiratory tract infection and su ...201728616497
chadox1 and mva based vaccine candidates against mers-cov elicit neutralising antibodies and cellular immune responses in mice.the middle east respiratory syndrome coronavirus (mers-cov) has infected more than 1900 humans, since 2012. the syndrome ranges from asymptomatic and mild cases to severe pneumonia and death. the virus is believed to be circulating in dromedary camels without notable symptoms since the 1980s. therefore, dromedary camels are considered the only animal source of infection. neither antiviral drugs nor vaccines are approved for veterinary or medical use despite active research on this area. here, we ...201728579232
reliable typing of mers-cov variants with a small genome fragment.middle east respiratory syndrome coronavirus (mers-cov) is an emerging pathogen that causes lower respiratory tract infection in humans. camels are the likely animal source for zoonotic infection, although exact transmission modes remain to be determined. human-to-human transmission occurs sporadically. the wide geographic distribution of mers-cov among dromedary camels and ongoing transmissions to humans provides concern for the evolution of a mers-cov variant with efficient human-to-human tran ...201525728084
human-dromedary camel interactions and the risk of acquiring zoonotic middle east respiratory syndrome coronavirus infection.middle east respiratory syndrome coronavirus (mers-cov) cases without documented contact with another human mers-cov case make up 61% (517/853) of all reported cases. these primary cases are of particular interest for understanding the source(s) and route(s) of transmission and for designing long-term disease control measures. dromedary camels are the only animal species for which there is convincing evidence that it is a host species for mers-cov and hence a potential source of human infections ...201625545147
middle east respiratory syndrome coronavirus (mers-cov): animal to human interaction.the middle east respiratory syndrome coronavirus (mers-cov) is a novel enzootic betacoronavirus that was first described in september 2012. the clinical spectrum of mers-cov infection in humans ranges from an asymptomatic or mild respiratory illness to severe pneumonia and multi-organ failure; overall mortality is around 35.7%. bats harbour several betacoronaviruses that are closely related to mers-cov but more research is needed to establish the relationship between bats and mers-cov. the serop ...201526924345
the sample of choice for detecting middle east respiratory syndrome coronavirus in asymptomatic dromedary camels using real-time reversetranscription polymerase chain reaction.the newly identified middle east respiratory syndrome coronavirus (mers-cov), which causes severe respiratory disease, particularly in people with comorbidities, requires further investigation. studies in qatar and elsewhere have provided evidence that dromedary camels are a reservoir for the virus, but the exact modes of transmission of mers-cov to humans remain unclear. in february 2014, an assessment was made of the suitability and sensitivity of different types of sample for the detection of ...201628332641
risk factors for primary middle east respiratory syndrome coronavirus illness in humans, saudi arabia, 2014.risk factors for primary middle east respiratory syndrome coronavirus (mers-cov) illness in humans are incompletely understood. we identified all primary mers-cov cases reported in saudi arabia during march-november 2014 by excluding those with history of exposure to other cases of mers-cov or acute respiratory illness of unknown cause or exposure to healthcare settings within 14 days before illness onset. using a case-control design, we assessed differences in underlying medical conditions and ...201626692185
asymptomatic mers-cov infection in humans possibly linked to infected dromedaries imported from oman to united arab emirates, may 2015.in may 2015 in united arab emirates, asymptomatic middle east respiratory syndrome coronavirus infection was identified through active case finding in 2 men with exposure to infected dromedaries. epidemiologic and virologic findings suggested zoonotic transmission. genetic sequences for viruses from the men and camels were similar to those for viruses recently detected in other countries.201526584223
abelson kinase inhibitors are potent inhibitors of severe acute respiratory syndrome coronavirus and middle east respiratory syndrome coronavirus fusion.the highly pathogenic severe acute respiratory syndrome coronavirus (sars-cov) and middle east respiratory syndrome coronavirus (mers-cov) cause significant morbidity and morality. there is currently no approved therapeutic for highly pathogenic coronaviruses, even as mers-cov is spreading throughout the middle east. we previously screened a library of fda-approved drugs for inhibitors of coronavirus replication in which we identified abelson (abl) kinase inhibitors, including the anticancer dru ...201627466418
unraveling the drivers of mers-cov transmission.with more than 1,700 laboratory-confirmed infections, middle east respiratory syndrome coronavirus (mers-cov) remains a significant threat for public health. however, the lack of detailed data on modes of transmission from the animal reservoir and between humans means that the drivers of mers-cov epidemics remain poorly characterized. here, we develop a statistical framework to provide a comprehensive analysis of the transmission patterns underlying the 681 mers-cov cases detected in the kingdom ...201627457935
presence of antibodies but no evidence for circulation of mers-cov in dromedaries on the canary islands, 2015.in 2012, a new betacoronavirus, middle east respiratory syndrome coronavirus (mers-cov), was identified in humans. several studies confirmed dromedary camels to be a potential reservoir and a source for human infection. camels located on the canary islands were included in those studies and ca 10% of them were positive for mers-cov-specific antibodies. however, these findings could not be correctly interpreted because epidemiological information was not provided. thus, further investigations wer ...201526536463
molecular aspects of mers-cov.middle east respiratory syndrome coronavirus (mers-cov) is a betacoronavirus which can cause acute respiratory distress in humans and is associated with a relatively high mortality rate. since it was first identified in a patient who died in a jeddah hospital in 2012, the world health organization has been notified of 1735 laboratory-confirmed cases from 27 countries, including 628 deaths. most cases have occurred in saudi arabia. mers-covancestors may be found in oldworld bats of the vespertili ...201728500431
mers-cov virus-like particles produced in insect cells induce specific humoural and cellular imminity in rhesus macaques.middle east respiratory syndrome coronavirus (mers-cov) causes severe respiratory disease in humans with a case fatality rate of over 39%, and poses a considerable threat to public health. a lack of approved vaccine or drugs currently constitutes a roadblock in controlling disease outbreak and spread. in this study, we generated mers-cov vlps using the baculovirus expression system. electron microscopy and immunoelectron microscopy results demonstrate that mers-cov vlps are structurally similar ...201727050368
middle east respiratory syndrome coronavirus vaccines: current status and novel approaches.middle east respiratory syndrome coronavirus (mers-cov) is a cause of severe respiratory infection in humans, specifically the elderly and people with comorbidities. the re-emergence of lethal coronaviruses calls for international collaboration to produce coronavirus vaccines, which are still lacking to date. ongoing efforts to develop mers-cov vaccines should consider the different target populations (dromedary camels and humans) and the correlates of protection. extending on our current knowle ...201728412285
further evidence for bats as the evolutionary source of middle east respiratory syndrome coronavirus.the evolutionary origins of middle east respiratory syndrome (mers) coronavirus (mers-cov) are unknown. current evidence suggests that insectivorous bats are likely to be the original source, as several 2c covs have been described from various species in the family vespertilionidae here, we describe a mers-like cov identified from a pipistrellus cf. hesperidus bat sampled in uganda (strain predict/pdf-2180), further supporting the hypothesis that bats are the evolutionary source of mers-cov. phy ...201728377531
development of dual taqman based one-step rrt-pcr assay panel for rapid and accurate diagnostic test of mers-cov: a novel human coronavirus, ahead of hajj pilgrimage.coronaviruses (covs) are large ribonucleic acid (rna) viruses causing primarily respiratory disease in humans. a novel human coronavirus, subsequently named middle east respiratory syndrome coronavirus (mers-cov), was first reported in saudi arabia in september of 2012. with increasing numbers of infections and deaths from mers-cov, development of a rapid and reliable kit was crucial to prevent further spread of mers-cov.201628191331
a camel-derived mers-cov with a variant spike protein cleavage site and distinct fusion activation properties.middle east respiratory syndrome coronavirus (mers-cov) continues to circulate in both humans and camels, and the origin and evolution of the virus remain unclear. here we characterize the spike protein of a camel-derived mers-cov (nrce-hku205) identified in 2013, early in the mers outbreak. nrce-hku205 spike protein has a variant cleavage motif with regard to the s2' fusion activation site-notably, a novel substitution of isoleucine for the otherwise invariant serine at the critical p1' cleavag ...201627999426
bartonella dromedarii sp. nov. isolated from domesticated camels (camelus dromedarius) in israel.bartonella spp. are fastidious, gram-negative bacilli that cause a wide spectrum of diseases in humans. most bartonella spp. have adapted to a specific host, generally a domestic or wild mammal. dromedary camels (camelus dromedarius) have become a focus of growing public-health interest because they have been identified as a reservoir host for the middle east respiratory syndrome coronavirus. nevertheless, data on camel zoonoses are limited. we aimed to study the occurrence of bartonella bactere ...201425409267
analysis of the genome sequence and prediction of b-cell epitopes of the envelope protein of middle east respiratory syndrome-coronavirus.the outbreak of middle east respiratory syndrome-coronavirus (mers-cov) in south korea in april 2015 led to 186 infections and 37 deaths by the end of october 2015. mers-cov was isolated from the imported patient in china. the envelope (e) protein, a small structural protein of mers-cov, plays an important role in host recognition and infection. to identify the conserved epitopes of the e protein, sequence analysis was performed by comparing the e proteins from 42 mers-cov strains that triggered ...201728574363
a screen of the nih clinical collection small molecule library identifies potential anti-coronavirus drugs.with the recent emergence of middle east respiratory syndrome coronavirus in humans and the outbreak of devastating porcine epidemic diarrhea coronavirus in swine, therapeutic intervention is urgently needed. however, anti-coronavirus drugs currently are not available. in an effort to assist rapid development of anti-coronavirus drugs, here we screened the nih clinical collection in cell culture using a luciferase reporter-expressing recombinant murine coronavirus. of the 727 compounds screened, ...201525451075
host species restriction of middle east respiratory syndrome coronavirus through its receptor, dipeptidyl peptidase 4.middle east respiratory syndrome coronavirus (mers-cov) emerged in 2012. recently, the mers-cov receptor dipeptidyl peptidase 4 (dpp4) was identified and the specific interaction of the receptor-binding domain (rbd) of mers-cov spike protein and dpp4 was determined by crystallography. animal studies identified rhesus macaques but not hamsters, ferrets, or mice to be susceptible for mers-cov. here, we investigated the role of dpp4 in this observed species tropism. cell lines of human and nonhuman ...201424899185
antibodies against mers coronavirus in dromedary camels, united arab emirates, 2003 and 2013.middle east respiratory syndrome coronavirus (mers-cov) has caused an ongoing outbreak of severe acute respiratory tract infection in humans in the arabian peninsula since 2012. dromedary camels have been implicated as possible viral reservoirs. we used serologic assays to analyze 651 dromedary camel serum samples from the united arab emirates; 151 of 651 samples were obtained in 2003, well before onset of the current epidemic, and 500 serum samples were obtained in 2013. recombinant spike prote ...201424655412
middle east respiratory syndrome coronavirus: epidemiology and disease control measures.the emergence of middle east respiratory syndrome coronavirus (mers-cov) infection in 2012 resulted in an increased concern of the spread of the infection globally. mers-cov infection had previously caused multiple health-care-associated outbreaks and resulted in transmission of the virus within families. community onset mers-cov cases continue to occur. dromedary camels are currently the most likely animal to be linked to human mers-cov cases. serologic tests showed significant infection in adu ...201425395865
[dromedary camels and middle east respiratory syndrome: mers coronavirus in the 'ship of the desert'].middle east respiratory syndrome coronavirus (mers-cov) is a novel coronavirus, identified in patients with respiratory symptoms in the middle east. accumulating evidence points to dromedary camels as being reservoirs. mers-cov has been isolated from dromedaries, and dromedary mers-cov is nearly identical to human mers-cov. camel and human mers-cov genome sequences from the same geographic areas cluster together. both on the arabian peninsula and in africa high percentages of adult dromedaries a ...201425248734
immunogenicity of an adenoviral-based middle east respiratory syndrome coronavirus vaccine in balb/c mice.a new type of coronavirus has been identified as the causative agent underlying middle east respiratory syndrome (mers). the mers coronavirus (mers-cov) has spread in the middle east, but cases originating in the middle east have also occurred in the european union and the usa. eight hundred and thirty-seven cases of mers-cov infection have been confirmed to date, including 291 deaths. mers-cov has infected dromedary camel populations in the middle east at high rates, representing an immediate s ...201425192975
middle east respiratory syndrome coronavirus quasispecies that include homologues of human isolates revealed through whole-genome analysis and virus cultured from dromedary camels in saudi arabia.abstract complete middle east respiratory syndrome coronavirus (mers-cov) genome sequences were obtained from nasal swabs of dromedary camels sampled in the kingdom of saudi arabia through direct analysis of nucleic acid extracts or following virus isolation in cell culture. consensus dromedary mers-cov genome sequences were the same with either template source and identical to published human mers-cov sequences. however, in contrast to individual human cases, where only clonal genomic sequences ...201424781747
novel betacoronavirus in dromedaries of the middle east, 2013.in 2013, a novel betacoronavirus was identified in fecal samples from dromedaries in dubai, united arab emirates. antibodies against the recombinant nucleocapsid protein of the virus, which we named dromedary camel coronavirus (dccov) uae-hku23, were detected in 52% of 59 dromedary serum samples tested. in an analysis of 3 complete dccov uae-hku23 genomes, we identified the virus as a betacoronavirus in lineage a1. the dccov uae-hku23 genome has g+c contents; a general preference for g/c in the ...201424655427
the heptad repeat region is a major selection target in mers-cov and related coronaviruses.middle east respiratory syndrome coronavirus (mers-cov) originated in bats and spread to humans via zoonotic transmission from camels. we analyzed the evolution of the spike (s) gene in betacoronaviruses (betacovs) isolated from different mammals, in bat coronavirus populations, as well as in mers-cov strains from the current outbreak. results indicated several positively selected sites located in the region comprising the two heptad repeats (hr1 and hr2) and their linker. two sites (r652 and v1 ...201526404138
a humanized neutralizing antibody against mers-cov targeting the receptor-binding domain of the spike protein.the newly-emerging middle east respiratory syndrome coronavirus (mers-cov) can cause severe and fatal acute respiratory disease in humans. despite global efforts, the potential for an associated pandemic in the future cannot be excluded. the development of effective counter-measures is urgent. mers-cov-specific anti-viral drugs or vaccines are not yet available. using the spike receptor-binding domain of mers-cov (mers-rbd) to immunize mice, we identified two neutralizing monoclonal antibodies ( ...201526391698
middle east respiratory syndrome coronavirus infection in dromedary camels in saudi arabia.the middle east respiratory syndrome (mers) is proposed to be a zoonotic disease; however, the reservoir and mechanism for transmission of the causative agent, the mers coronavirus, are unknown. dromedary camels have been implicated through reports that some victims have been exposed to camels, camels in areas where the disease has emerged have antibodies to the virus, and viral sequences have been recovered from camels in association with outbreaks of the disease among humans. nonetheless, whet ...201424570370
middle east respiratory syndrome coronavirus (mers-cov): evidence and speculations.in 2012, a novel human coronavirus emerged and was tentatively named "middle east respiratory syndrome coronavirus" (mers-cov). the high mortality rate of mers-cov focused attention on the ecology of the virus. it has been found that mers-cov belongs to the group c lineage of the genus betacoronavirus. coronavirus surveillance studies in different populations of bats have suggested that they are probable reservoirs for this novel virus, and phylogenetic analysis of both the spike (s1) and rna-de ...201424515532
structural basis for the neutralization of mers-cov by a human monoclonal antibody mers-27.the recently reported middle east respiratory syndrome coronavirus (mers-cov) causes severe respiratory illness in humans with an approximately 30% mortality rate. the envelope spike glycoprotein on the surface of mers-cov mediates receptor binding, membrane fusion, and viral entry. we previously reported two human monoclonal antibodies that target the receptor binding domain (rbd) of the spike and exhibit strong neutralization activity against live and pesudotyped mers-cov infection. here we de ...201526281793
middle-east respiratory syndrome coronavirus: is it worth a world panic?in 2012 middle-east respiratory syndrome coronavirus (mers-cov) was evolved in the arabian peninsula. tremendous and successful efforts have been conducted to discover the genome structure, epidemiology, clinical signs, pathogenesis, diagnosis and antiviral therapy. taphozous perforatus bats are the incriminated reservoir host and camels are the currently confirmed animal linker. the virus resulted in less than 1000 infected cases and 355 deaths. the case fatality rate of the mers-cov is high, h ...201526279980
receptor variation and susceptibility to middle east respiratory syndrome coronavirus infection.the middle east respiratory syndrome coronavirus (mers-cov) recently spread from an animal reservoir to infect humans, causing sporadic severe and frequently fatal respiratory disease. appropriate public health and control measures will require discovery of the zoonotic mers coronavirus reservoirs. the relevant animal hosts are liable to be those that offer optimal mers virus cell entry. cell entry begins with virus spike (s) protein binding to dpp4 receptors. we constructed chimeric dpp4 recept ...201424554656
a mouse model for mers coronavirus-induced acute respiratory distress syndrome.middle east respiratory syndrome coronavirus (mers-cov) is a novel virus that emerged in 2012, causing acute respiratory distress syndrome (ards), severe pneumonia-like symptoms and multi-organ failure, with a case fatality rate of ∼36%. limited clinical studies indicate that humans infected with mers-cov exhibit pathology consistent with the late stages of ards, which is reminiscent of the disease observed in patients infected with severe acute respiratory syndrome coronavirus. models of mers-c ...201627892925
animal models for sars and mers coronaviruses.the emergence of severe acute respiratory syndrome coronavirus (sars-cov) and middle east respiratory syndrome coronavirus (mers-cov), two strains of animal coronaviruses that crossed the species barrier to infect and cause severe respiratory infections in humans within the last 12 years, have taught us that coronaviruses represent a global threat that does not recognize international borders. we can expect to see other novel coronaviruses emerge in the future. an ideal animal model should refle ...201526184451
two mutations were critical for bat-to-human transmission of middle east respiratory syndrome coronavirus.to understand how middle east respiratory syndrome coronavirus (mers-cov) transmitted from bats to humans, we compared the virus surface spikes of mers-cov and a related bat coronavirus, hku4. although hku4 spike cannot mediate viral entry into human cells, two mutations enabled it to do so by allowing it to be activated by human proteases. these mutations are present in mers-cov spike, explaining why mers-cov infects human cells. these mutations therefore played critical roles in the bat-to-hum ...201526063432
emerging respiratory tract viral infections.this article reviews the clinical and treatment aspects of avian influenza viruses and the middle east respiratory syndrome coronavirus (mers-cov).201525764021
the middle east respiratory syndrome coronavirus - a continuing risk to global health security.two new zoonotic coronaviruses causing disease in humans (zumla et al. 2015a; hui and zumla 2015; peiris et al. 2003; yu et al. 2014) have been the focus of international attention for the past 14 years due to their epidemic potential; (1) the severe acute respiratory syndrome coronavirus (sars-cov) (peiris et al. 2003) first discovered in china in 2001 caused a major global epidemic of the severe acute respiratory syndrome (sars). (2) the middle east respiratory syndrome coronavirus (mers-cov) ...201727966107
inactivation and safety testing of middle east respiratory syndrome coronavirus.middle east respiratory syndrome coronavirus (mers-cov) is a recently emerged virus that has caused a number of human infections and deaths, primarily in the middle east. the transmission of mers-cov to humans has been proposed to be as a result of contact with camels, but evidence of human-to-human transmission also exists. in order to work with mers-cov in a laboratory setting, the us centers for disease control and prevention (cdc) has determined that mers-cov should be handled at a biosafety ...201526190637
influenza a and b viruses but not mers-cov in hajj pilgrims, austria, 2014. 201525811672
biochemical characterization of middle east respiratory syndrome coronavirus helicase.middle east respiratory syndrome coronavirus (mers-cov) helicase is a superfamily 1 helicase containing seven conserved motifs. we have cloned, expressed, and purified a strep-fused recombinant mers-cov nonstructural protein 13 (m-nsp13) helicase. characterization of its biochemical properties showed that it unwound dna and rna similarly to severe acute respiratory syndrome cov nsp13 (s-nsp13) helicase. we showed that m-nsp13 unwound in a 5'-to-3' direction and efficiently unwound the partially ...201727631026
feasibility of using convalescent plasma immunotherapy for mers-cov infection, saudi arabia.we explored the feasibility of collecting convalescent plasma for passive immunotherapy of middle east respiratory syndrome coronavirus (mers-cov) infection by using elisa to screen serum samples from 443 potential plasma donors: 196 patients with suspected or laboratory-confirmed mers-cov infection, 230 healthcare workers, and 17 household contacts exposed to mers-cov. elisa-reactive samples were further tested by indirect fluorescent antibody and microneutralization assays. of the 443 tested s ...201627532807
mers-cov spike protein: targets for vaccines and therapeutics.the disease outbreak caused by middle east respiratory syndrome coronavirus (mers-cov) is still ongoing in the middle east. over 1700 people have been infected since it was first reported in september 2012. despite great efforts, licensed vaccines or therapeutics against mers-cov remain unavailable. the mers-cov spike (s) protein is an important viral antigen known to mediate host-receptor binding and virus entry, as well as induce robust humoral and cell-mediated responses in humans during infe ...201627468951
middle east respiratory syndrome: knowledge to date.to provide a conceptual and clinical review of middle east respiratory syndrome.201525785521
single-dose treatment with a humanized neutralizing antibody affords full protection of a human transgenic mouse model from lethal middle east respiratory syndrome (mers)-coronavirus infection.middle east respiratory syndrome coronavirus (mers-cov) is continuously spreading and causing severe and fatal acute respiratory disease in humans. prophylactic and therapeutic strategies are therefore urgently needed to control mers-cov infection. here, we generated a humanized monoclonal antibody (mab), designated hms-1, which targeted the mers-cov receptor-binding domain (rbd) with high affinity. hms-1 significantly blocked mers-cov rbd binding to its viral receptor, human dipeptidyl peptidas ...201627312105
middle east respiratory syndrome coronavirus: transmission and phylogenetic evolution.the middle east respiratory syndrome coronavirus (mers-cov) was first described in 2012 and, subsequently, many cases were reported with a lower case fatality rate than initial cases. humans can become infected within their communities and transmission can then be amplified in the healthcare setting. contact investigation among cases shows a variable amount of spread among family members and healthcare workers. so far, circulating virus strains remain similar under continuous monitoring, with no ...201425178651
receptor usage and cell entry of bat coronavirus hku4 provide insight into bat-to-human transmission of mers coronavirus.middle east respiratory syndrome coronavirus (mers-cov) currently spreads in humans and causes ∼ 36% fatality in infected patients. believed to have originated from bats, mers-cov is genetically related to bat coronaviruses hku4 and hku5. to understand how bat coronaviruses transmit to humans, we investigated the receptor usage and cell entry activity of the virus-surface spike proteins of hku4 and hku5. we found that dipeptidyl peptidase 4 (dpp4), the receptor for mers-cov, is also the receptor ...201425114257
coronaviruses: severe acute respiratory syndrome coronavirus and middle east respiratory syndrome coronavirus in travelers.middle east respiratory syndrome coronavirus (mers-cov) is currently the focus of global attention. in this review, we describe virological, clinical, epidemiological features and interim travel advice and guidelines regarding mers-cov. we compare and contrast these with the severe acute respiratory syndrome coronavirus (sars-cov).201425033169
epidemiology of a novel recombinant middle east respiratory syndrome coronavirus in humans in saudi arabia.middle east respiratory syndrome coronavirus (mers-cov) causes severe respiratory illness in humans. fundamental questions about circulating viruses and transmission routes remain.201627302191
antiviral drugs specific for coronaviruses in preclinical development.coronaviruses are positive stranded rna viruses that cause respiratory, enteric and central nervous system diseases in many species, including humans. until recently, the relatively low burden of disease in humans caused by few of these viruses impeded the development of coronavirus specific therapeutics. however, the emergence of severe acute respiratory syndrome coronavirus (sars-cov), and more recently, middle east respiratory syndrome coronavirus (mers-cov), has impelled the development of s ...201424997250
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