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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
host-directed therapies for improving poor treatment outcomes associated with the middle east respiratory syndrome coronavirus infections.three years after its first discovery in jeddah saudi arabia, the novel zoonotic pathogen of humans, the middle east respiratory syndrome coronavirus (mers-cov) continues to be a major threat to global health security.(1) sporadic community acquired cases of mers continue to be reported from the middle east. the recent nosocomial outbreaks in hospitals in seoul, korea and at the national guard hospital in riyadh, saudi arabia indicate the epidemic potential of mers-cov. currently there are no ef ...201526365771
origin and possible genetic recombination of the middle east respiratory syndrome coronavirus from the first imported case in china: phylogenetics and coalescence analysis.the middle east respiratory syndrome coronavirus (mers-cov) causes a severe acute respiratory tract infection with a high fatality rate in humans. coronaviruses are capable of infecting multiple species and can evolve rapidly through recombination events. here, we report the complete genomic sequence analysis of a mers-cov strain imported to china from south korea. the imported virus, provisionally named chinagd01, belongs to group 3 in clade b in the whole-genome phylogenetic tree and also has ...201526350969
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
bat-to-human: spike features determining 'host jump' of coronaviruses sars-cov, mers-cov, and beyond.both severe acute respiratory syndrome coronavirus (sars-cov) and middle east respiratory syndrome coronavirus (mers-cov) are zoonotic pathogens that crossed the species barriers to infect humans. the mechanism of viral interspecies transmission is an important scientific question to be addressed. these coronaviruses contain a surface-located spike (s) protein that initiates infection by mediating receptor-recognition and membrane fusion and is therefore a key factor in host specificity. in addi ...201526206723
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
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
influenza a and b viruses but not mers-cov in hajj pilgrims, austria, 2014. 201525811672
middle east respiratory syndrome: knowledge to date.to provide a conceptual and clinical review of middle east respiratory syndrome.201525785521
middle east respiratory syndrome coronavirus (mers-cov): prevention in travelers.middle east respiratory syndrome coronavirus (mers-cov), a novel coronavirus that causes a severe lower respiratory tract infection in humans, emerged in the middle east in 2012. since then, mers-cov has caused an ongoing epidemic in the arabian peninsula with sporadic cases imported in europe, north africa, southeast asia, and the united states of america. as of 28th may 2014, 636 laboratory-confirmed cases of infection with mers-cov have been reported to world health organization including 14 ...201625457301
receptor-binding domain-based subunit vaccines against mers-cov.development of effective vaccines, in particular, subunit-based vaccines, against emerging middle east respiratory syndrome (mers) caused by the mers coronavirus (mers-cov) will provide the safest means of preventing the continuous spread of mers in humans and camels. this review briefly describes the structure of the mers-cov spike (s) protein and its receptor-binding domain (rbd), discusses the current status of mers vaccine development and illustrates the strategies used to develop rbd-based ...201525445336
detecting differential transmissibilities that affect the size of self-limited outbreaks.our ability to respond appropriately to infectious diseases is enhanced by identifying differences in the potential for transmitting infection between individuals. here, we identify epidemiological traits of self-limited infections (i.e. infections with an effective reproduction number satisfying [0 < r eff < 1) that correlate with transmissibility. our analysis is based on a branching process model that permits statistical comparison of both the strength and heterogeneity of transmission for tw ...201425356657
pathogenesis of middle east respiratory syndrome coronavirus.human coronaviruses (covs) mostly cause a common cold that is mild and self-limiting. zoonotic transmission of covs such as the recently identified middle east respiratory syndrome (mers)-cov and severe acute respiratory syndrome (sars)-cov, on the other hand, may be associated with severe lower respiratory tract infection. this article reviews the clinical and pathological data available on mers and compares it to sars. most importantly, chest radiographs and imaging results of patients with me ...201525294366
host cell entry of middle east respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein.middle east respiratory syndrome coronavirus (mers-cov) is a newly identified betacoronavirus causing high morbidity and mortality in humans. the coronavirus spike (s) protein is the main determinant of viral entry, and although it was previously shown that mers-cov s can be activated by various proteases, the details of the mechanisms of proteolytic activation of fusion are still incompletely characterized. here, we have uncovered distinctive characteristics of mers-cov s. we identify, by bioin ...201425288733
ifitm proteins inhibit entry driven by the mers-coronavirus spike protein: evidence for cholesterol-independent mechanisms.the interferon-inducible transmembrane (ifitm) proteins 1, 2 and 3 inhibit the host cell entry of several enveloped viruses, potentially by promoting the accumulation of cholesterol in endosomal compartments. ifitm3 is essential for control of influenza virus infection in mice and humans. in contrast, the role of ifitm proteins in coronavirus infection is less well defined. employing a retroviral vector system for analysis of coronavirus entry, we investigated the susceptibility of human-adapted ...201425256397
searching for an ideal vaccine candidate among different mers coronavirus receptor-binding fragments--the importance of immunofocusing in subunit vaccine design.the newly emerged middle east respiratory syndrome coronavirus (mers-cov) is currently spreading among humans, making development of effective mers vaccines a high priority. a defined receptor-binding domain (rbd) in mers-cov spike protein can potentially serve as a subunit vaccine candidate against mers-cov infections. to identify an ideal vaccine candidate, we have constructed five different versions of rbd fragments, s350-588-fc, s358-588-fc, s367-588-fc, s367-606-fc, and s377-588-fc (their n ...201425240756
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
rooting the phylogenetic tree of middle east respiratory syndrome coronavirus by characterization of a conspecific virus from an african bat.the emerging middle east respiratory syndrome coronavirus (mers-cov) causes lethal respiratory infections mainly on the arabian peninsula. the evolutionary origins of mers-cov are unknown. we determined the full genome sequence of a cov directly from fecal material obtained from a south african neoromicia capensis bat (neocov). neocov shared essential details of genome architecture with mers-cov. eighty-five percent of the neocov genome was identical to mers-cov at the nucleotide level. based on ...201425031349
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
unanswered questions about the middle east respiratory syndrome coronavirus (mers-cov).the middle east respiratory syndrome coronavirus (mers-cov) represents a current threat to the arabian peninsula, and potential pandemic disease. as of june 3, 2014, mers cov has reportedly infected 688 people and killed 282. we briefly summarize the state of the outbreak, and highlight unanswered questions and various explanations for the observed epidemiology.201424920393
t cell-mediated immune response to respiratory coronaviruses.emerging respiratory coronaviruses such as the severe acute respiratory syndrome coronavirus (sars-cov) and middle east respiratory syndrome coronavirus (mers-cov) pose potential biological threats to humans. sars and mers are manifested as severe atypical pneumonia associated with high morbidity and mortality in humans. the majority of studies carried out in sars-cov-infected humans and animals attribute a dysregulated/exuberant innate response as a leading contributor to sars-cov-mediated path ...201424845462
exceptionally potent neutralization of middle east respiratory syndrome coronavirus by human monoclonal antibodies.the recently discovered middle east respiratory syndrome coronavirus (mers-cov) continues to infect humans, with high mortality. specific, highly effective therapeutics and vaccines against the mers-cov are urgently needed to save human lives and address the pandemic concerns. we identified three human monoclonal antibodies (mabs), m336, m337, and m338, targeting the receptor (cd26/dpp4) binding domain (rbd) of the mers-cov spike glycoprotein from a very large naïve-antibody library (containing ...201424789777
potent neutralization of mers-cov by human neutralizing monoclonal antibodies to the viral spike glycoprotein.the recently identified middle east respiratory syndrome coronavirus (mers-cov) causes severe and fatal acute respiratory illness in humans. however, no prophylactic and therapeutic agents specifically against mers-cov are currently available. entry of mers-cov into target cells depends on binding of the receptor binding domain (rbd) of the viral envelope spike glycoprotein to the cellular receptor dipeptidyl peptidase 4 (dpp4). we report the isolation and characterization of two potent human rb ...201424778414
a conformation-dependent neutralizing monoclonal antibody specifically targeting receptor-binding domain in middle east respiratory syndrome coronavirus spike protein.prophylactic and therapeutic strategies are urgently needed to combat infections caused by the newly emerged middle east respiratory syndrome coronavirus (mers-cov). here, we have developed a neutralizing monoclonal antibody (mab), designated mersmab1, which potently blocks mers-cov entry into human cells. biochemical assays reveal that mersmab1 specifically binds to the receptor-binding domain (rbd) of the mers-cov spike protein and thereby competitively blocks the binding of the rbd to its cel ...201424719424
distinct immune response in two mers-cov-infected patients: can we go from bench to bedside?one year after the occurrence of the first case of infection by the middle east respiratory syndrome coronavirus (mers-cov) there is no clear consensus on the best treatment to propose. the world health organization, as well as several other national agencies, are still working on different clinical approaches to implement the most relevant treatment in mers-cov infection. we compared innate and adaptive immune responses of two patients infected with mers-cov to understand the underlying mechani ...201424551142
reverse transcription recombinase polymerase amplification assay for the detection of middle east respiratory syndrome coronavirus.the emergence of middle east respiratory syndrome coronavirus (mers-cov) in the eastern mediterranean and imported cases to europe has alerted public health authorities. currently, detection of mers-cov in patient samples is done by real-time rt-pcr. samples collected from suspected cases are sent to highly-equipped centralized laboratories for screening. a rapid point-of-care test is needed to allow more widespread mobile detection of the virus directly from patient material. in this study, we ...201324459611
proteolytic processing, deubiquitinase and interferon antagonist activities of middle east respiratory syndrome coronavirus papain-like protease.the emerging middle east respiratory syndrome coronavirus (mers-cov) causes severe pulmonary disease in humans and represents the second example of a highly pathogenic coronavirus (cov) following severe acute respiratory syndrome coronavirus (sars-cov). genomic studies revealed that two viral proteases, papain-like protease (plpro) and 3c-like protease (3clpro), process the polyproteins encoded by the mers-cov genomic rna. we previously reported that sars-cov plpro acts as both deubiquitinase (d ...201424362959
interferon-β and mycophenolic acid are potent inhibitors of middle east respiratory syndrome coronavirus in cell-based assays.the middle east respiratory syndrome coronavirus (mers-cov) presents a novel emerging threat to public health worldwide. several treatments for infected individuals have been suggested including ifn, ribavirin and passive immunotherapy with convalescent plasma. administration of ifn-α2b and ribavirin has improved outcomes of mers-cov infection in rhesus macaques when administered within 8 h post-challenge. however, detailed and systematic evidence on the activity of other clinically available dr ...201424323636
lack of mers coronavirus neutralizing antibodies in humans, eastern province, saudi arabia.we used a lentiviral vector bearing the viral spike protein to detect neutralizing antibodies against middle east respiratory syndrome coronavirus (mers-cov) in persons from the eastern province of saudi arabia. none of the 268 samples tested displayed neutralizing activity, which suggests that mers-cov infections in humans are infrequent in this province.201324274664
state of knowledge and data gaps of middle east respiratory syndrome coronavirus (mers-cov) in humans.between september 2012 and 22 october 2013, 144 laboratory-confirmed and 17 probable mers-cov cases from nine countries were notified to who.201324270606
isolation and characterization of a bat sars-like coronavirus that uses the ace2 receptor.the 2002-3 pandemic caused by severe acute respiratory syndrome coronavirus (sars-cov) was one of the most significant public health events in recent history. an ongoing outbreak of middle east respiratory syndrome coronavirus suggests that this group of viruses remains a key threat and that their distribution is wider than previously recognized. although bats have been suggested to be the natural reservoirs of both viruses, attempts to isolate the progenitor virus of sars-cov from bats have bee ...201324172901
middle east respiratory syndrome coronavirus (mers-cov) causes transient lower respiratory tract infection in rhesus macaques.in 2012, a novel betacoronavirus, designated middle east respiratory syndrome coronavirus or mers-cov and associated with severe respiratory disease in humans, emerged in the arabian peninsula. to date, 108 human cases have been reported, including cases of human-to-human transmission. the availability of an animal disease model is essential for understanding pathogenesis and developing effective countermeasures. upon a combination of intratracheal, ocular, oral, and intranasal inoculation with ...201324062443
engineering a replication-competent, propagation-defective middle east respiratory syndrome coronavirus as a vaccine candidate.middle east respiratory syndrome coronavirus (mers-cov) is an emerging coronavirus infecting humans that is associated with acute pneumonia, occasional renal failure, and a high mortality rate and is considered a threat to public health. the construction of a full-length infectious cdna clone of the mers-cov genome in a bacterial artificial chromosome is reported here, providing a reverse genetics system to study the molecular biology of the virus and to develop attenuated viruses as vaccine can ...201324023385
tracing the sars-coronavirus.four coronaviruses (hcov-229e, hcov-oc43, hcov-nl63, hcov-hku1) are endemic in humans and mainly associated with mild respiratory illnesses; whereas the other two coronaviruses [severe acute respiratory syndrome coronavirus (sars-cov) and middle east respiratory syndrome coronavirus (mers-cov)] present as emerging infections causing severe respiratory syndrome. coronaviruses evolve by accumulation of point mutations and recombination of genomes among different strains or species. mammalian coron ...201323977431
spiking the mers-coronavirus receptor.a novel coronavirus, the middle east respiratory syndrome coronavirus, recently emerged through zoonotic transmission, causing a severe lower respiratory tract infection in humans. in two recent papers, one published in cell research, the crystal structure of the viral receptor-binding domain in complex with the host cd26/dipeptidyl peptidase 4 receptor has now been characterized.201323938293
crystal structure of the receptor-binding domain from newly emerged middle east respiratory syndrome coronavirus.the newly emerged middle east respiratory syndrome coronavirus (mers-cov) has infected at least 77 people, with a fatality rate of more than 50%. alarmingly, the virus demonstrates the capability of human-to-human transmission, raising the possibility of global spread and endangering world health and economy. here we have identified the receptor-binding domain (rbd) from the mers-cov spike protein and determined its crystal structure. this study also presents a structural comparison of mers-cov ...201323903833
the emerging novel middle east respiratory syndrome coronavirus: the "knowns" and "unknowns".a novel lineage c betacoronavirus, originally named human coronavirus emc/2012 (hcov-emc) and recently renamed middle east respiratory syndrome coronavirus (mers-cov), that is phylogenetically closely related to tylonycteris bat coronavirus hku4 and pipistrellus bat coronavirus hku5, which we discovered in 2007 from bats in hong kong, has recently emerged in the middle east to cause a severe acute respiratory syndrome (sars)-like infection in humans. the first laboratory-confirmed case, which in ...201323883791
molecular basis of binding between novel human coronavirus mers-cov and its receptor cd26.the newly emergent middle east respiratory syndrome coronavirus (mers-cov) can cause severe pulmonary disease in humans, representing the second example of a highly pathogenic coronavirus, the first being sars-cov. cd26 (also known as dipeptidyl peptidase 4, dpp4) was recently identified as the cellular receptor for mers-cov. the engagement of the mers-cov spike protein with cd26 mediates viral attachment to host cells and virus-cell fusion, thereby initiating infection. here we delineate the mo ...201323831647
update: severe respiratory illness associated with middle east respiratory syndrome coronavirus (mers-cov)--worldwide, 2012-2013.cdc continues to work in consultation with the world health organization (who) and other partners to better understand the public health risk posed by the middle east respiratory syndrome coronavirus (mers-cov), formerly known as novel coronavirus, which was first reported to cause human infection in september 2012. the continued reporting of new cases indicates that there is an ongoing risk for transmission to humans in the area of the arabian peninsula. new reports of cases outside the region ...201323760190
mers-coronavirus replication induces severe in vitro cytopathology and is strongly inhibited by cyclosporin a or interferon-α treatment.coronavirus (cov) infections are commonly associated with respiratory and enteric disease in humans and animals. the 2003 outbreak of severe acute respiratory syndrome (sars) highlighted the potentially lethal consequences of cov-induced disease in humans. in 2012, a novel cov (middle east respiratory syndrome coronavirus; mers-cov) emerged, causing 49 human cases thus far, of which 23 had a fatal outcome. in this study, we characterized mers-cov replication and cytotoxicity in human and monkey ...201323620378
histopathology of middle east respiratory syndrome coronovirus (mers-cov) infection - clinicopathological and ultrastructural study.the pathogenesis, viral localization and histopathological features of middle east respiratory syndrome - coronavirus (mers-cov) in human are not sufficiently described. the aims of this study were to explore and define the spectrum of histological and ultrastructural pathological changes affecting various organs in a patient with mers-cov infection and represent a base of mers-cov histopathology.201728858401
enhanced inflammation in new zealand white rabbits when mers-cov reinfection occurs in the absence of neutralizing antibody.the middle east respiratory syndrome coronavirus (mers-cov) is a zoonotic betacoronavirus that was first detected in humans in 2012 as a cause of severe acute respiratory disease. as of july 28, 2017, there have been 2,040 confirmed cases with 712 reported deaths. while many infections have been fatal, there have also been a large number of mild or asymptomatic cases discovered through monitoring and contact tracing. new zealand white rabbits are a possible model for asymptomatic infection with ...201728817732
comparative genomic analysis mers cov isolated from humans and camels with special reference to virus encoded helicase.middle east respiratory syndrome coronavirus (mers cov) is a new emerging viral disease characterized by high fatality rate. understanding mers cov genetic aspects and codon usage pattern is important to understand mers cov survival, adaptation, evolution, resistance to innate immunity, and help in finding the unique aspects of the virus for future drug discovery experiments. in this work, we provide comprehensive analysis of 238 mers cov full genomes comprised of human (hmers) and camel (cmers) ...201728769010
mers-cov infection in humans is associated with a pro-inflammatory th1 and th17 cytokine profile.the middle east respiratory syndrome coronavirus (mers-cov) has been recognized as a highly pathogenic virus to humans that infects the respiratory tract and is associated with high morbidity and mortality. studies in animal models suggest that mers-cov infection induces a strong inflammatory response, which may be related to the severity of disease. data showing the cytokine profiles in humans during the acute phase of mers-cov infection are limited. in this study, we have analyzed the profile ...201829414327
the prevalence of middle east respiratory syndrome coronavirus (mers-cov) infection in livestock and temporal relation to locations and seasons.the middle east respiratory syndrome (mers) has been reported for the first time infecting a human being since 2012. the who was notified of 27 countries have reported cases of mers, the majority of these cases occur in the arabian peninsula, particularly in saudi arabia. dromedary camels are likely to be the main source of middle east respiratory syndrome virus (mers-cov) infection in humans.201829396257
mers-cov spillover at the camel-human interface.middle east respiratory syndrome coronavirus (mers-cov) is a zoonotic virus from camels causing significant mortality and morbidity in humans in the arabian peninsula. the epidemiology of the virus remains poorly understood, and while case-based and seroepidemiological studies have been employed extensively throughout the epidemic, viral sequence data have not been utilised to their full potential. here, we use existing mers-cov sequence data to explore its phylodynamics in two of its known majo ...201829336306
protective efficacy of a novel simian adenovirus vaccine against lethal mers-cov challenge in a transgenic human dpp4 mouse model.middle east respiratory syndrome coronavirus (mers-cov) is a novel zoonotic virus that causes severe respiratory disease in humans with a case fatality rate close to 40%, but for which no vaccines are available. here, we evaluated the utility of chadox1, a promising replication-deficient simian adenovirus vaccine vector platform with an established safety profile in humans and dromedary camels, for mers-cov vaccine development. using a transgenic lethal balb/c mers-cov mouse model we showed that ...201729263883
detection and full genome characterization of two beta cov viruses related to middle east respiratory syndrome from bats in italy.middle east respiratory syndrome coronavirus (mers-cov), which belongs to beta group of coronavirus, can infect multiple host species and causes severe diseases in humans. multiple surveillance and phylogenetic studies suggest a bat origin. in this study, we describe the detection and full genome characterization of two covs closely related to mers-cov from two italian bats, pipistrellus kuhlii and hypsugo savii.201729258555
a recombinant vsv-vectored mers-cov vaccine induces neutralizing antibody and t cell responses in rhesus monkeys after single dose immunization.middle east respiratory syndrome coronavirus (mers-cov) has been a highly threatening zoonotic pathogen since its outbreak in 2012. similar to sars-cov, mers-cov belongs to the coronavirus family and can induce severe respiratory symptoms in humans, with an average case fatality rate of 35% according to the world health organization. spike (s) protein of mers-cov is immunogenic and can induce neutralizing antibodies, thus is a potential major target for vaccine development. here we constructed a ...201829246504
identification of alpha and beta coronavirus in wildlife species in france: bats, rodents, rabbits, and hedgehogs.coronaviruses are closely monitored in the context of emerging diseases and, as illustrated with severe acute respiratory syndrome coronavirus (sars-cov) and middle east respiratory syndrome-coronavirus (mers-cov), are known to cross the species barrier and eventually to move from wildlife to humans. knowledge of the diversity of coronaviruses in wildlife is therefore essential to better understand and prevent emergence events. this study explored the presence of coronaviruses in four wild mamma ...201729186061
expression and cleavage of middle east respiratory syndrome coronavirus nsp3-4 polyprotein induce the formation of double-membrane vesicles that mimic those associated with coronaviral rna replication.betacoronaviruses, such as middle east respiratory syndrome coronavirus (mers-cov), are important pathogens causing potentially lethal infections in humans and animals. coronavirus rna synthesis is thought to be associated with replication organelles (ros) consisting of modified endoplasmic reticulum (er) membranes. these are transformed into double-membrane vesicles (dmvs) containing viral double-stranded rna and into other membranous elements such as convoluted membranes, together forming a re ...201729162711
middle east respiratory syndrome coronavirus nonstructural protein 16 is necessary for interferon resistance and viral pathogenesis.coronaviruses (covs) encode a mixture of highly conserved and novel genes, as well as genetic elements necessary for infection and pathogenesis, raising the possibility of common targets for attenuation and therapeutic design. in this study, we focused on highly conserved nonstructural protein 16 (nsp16), a viral 2'o-methyltransferase (2'o-mtase) that encodes critical functions in immune modulation and infection. using reverse genetics, we disrupted a key motif in the conserved kdke motif of mid ...201729152578
diversity of middle east respiratory syndrome coronaviruses in 109 dromedary camels based on full-genome sequencing, abu dhabi, united arab emirates.middle east respiratory syndrome coronavirus (mers-cov) was identified on the arabian peninsula in 2012 and is still causing cases and outbreaks in the middle east. when mers-cov was first identified, the closest related virus was in bats; however, it has since been recognized that dromedary camels serve as a virus reservoir and potential source for human infections. a total of 376 camels were screened for mers-cov at a live animal market in the eastern region of the emirate of abu dhabi, uae. i ...201729116217
knowledge and awareness of middle east respiratory syndrome coronavirus among saudi and non-saudi arabian pilgrims.the current study was intended to evaluate the knowledge and awareness toward middle east respiratory syndrome coronavirus (mers-cov) of pilgrims from saudi arabia and from different arabian countries.201729114190
dpp4, the middle east respiratory syndrome coronavirus receptor, is upregulated in lungs of smokers and chronic obstructive pulmonary disease patients.middle east respiratory syndrome coronavirus (mers-cov) causes pneumonia with a relatively high case fatality rate in humans. smokers and chronic obstructive pulmonary disease (copd) patients have been reported to be more susceptible to mers-cov infection. here, we determined the expression of mers-cov receptor, dipeptidyl peptidase iv (dpp4), in lung tissues of smokers without airflow limitation and copd patients in comparison to nonsmoking individuals (never-smokers).201829020176
cross-sectional study of mers-cov-specific rna and antibodies in animals that have had contact with mers patients in saudi arabia.middle east respiratory syndrome coronavirus (mers-cov) is a newly emerged coronavirus that is associated with a severe respiratory disease in humans in the middle east. the epidemiological profiles of the mers-cov infections suggest zoonotic transmission from an animal reservoir to humans.201728993171
identification of sialic acid-binding function for the middle east respiratory syndrome coronavirus spike glycoprotein.middle east respiratory syndrome coronavirus (mers-cov) targets the epithelial cells of the respiratory tract both in humans and in its natural host, the dromedary camel. virion attachment to host cells is mediated by 20-nm-long homotrimers of spike envelope protein s. the n-terminal subunit of each s protomer, called s1, folds into four distinct domains designated s1athrough s1dbinding of mers-cov to the cell surface entry receptor dipeptidyl peptidase 4 (dpp4) occurs via s1bwe now demonstrate ...201728923942
identification of diverse viruses in upper respiratory samples in dromedary camels from united arab emirates.camels are known carriers for many viral pathogens, including middle east respiratory syndrome coronavirus (mers-cov). it is likely that there are additional, as yet unidentified viruses in camels with the potential to cause disease in humans. in this study, we performed metagenomic sequencing analysis on nasopharyngeal swab samples from 108 mers-cov-positive dromedary camels from a live animal market in abu dhabi, united arab emirates. we obtained a total of 846.72 million high-quality reads fr ...201728902913
human coronaviruses: a review of virus-host interactions.human coronaviruses (hcovs) are known respiratory pathogens associated with a range of respiratory outcomes. in the past 14 years, the onset of severe acute respiratory syndrome coronavirus (sars-cov) and middle east respiratory syndrome coronavirus (mers-cov) have thrust hcovs into spotlight of the research community due to their high pathogenicity in humans. the study of hcov-host interactions has contributed extensively to our understanding of hcov pathogenesis. in this review, we discuss som ...201628933406
importance of neutralizing monoclonal antibodies targeting multiple antigenic sites on mers-cov spike to avoid neutralization escape.middle east respiratory syndrome coronavirus (mers-cov) causes a highly lethal pulmonary infection with ∼35% mortality. the potential for a future pandemic originating from animal reservoirs or healthcare-associated events is a major public health concern. there are no vaccines or therapeutic agents currently available for mers-cov. using a probe-based single b cell-cloning strategy, we have identified and characterized multiple neutralizing mabs specifically binding to the receptor binding doma ...201829514901
coronavirus susceptibility to the antiviral remdesivir (gs-5734) is mediated by the viral polymerase and the proofreading exoribonuclease.emerging coronaviruses (covs) cause severe disease in humans, but no approved therapeutics are available. the cov nsp14 exoribonuclease (exon) has complicated development of antiviral nucleosides due to its proofreading activity. we recently reported that the nucleoside analogue gs-5734 (remdesivir) potently inhibits human and zoonotic covsin vitroand in a severe acute respiratory syndrome coronavirus (sars-cov) mouse model. however, studies with gs-5734 have not reported resistance associated w ...201829511076
mers-cov: understanding the latest human coronavirus threat.human coronaviruses cause both upper and lower respiratory tract infections in humans. in 2012, a sixth human coronavirus (hcov) was isolated from a patient presenting with severe respiratory illness. the 60-year-old man died as a result of renal and respiratory failure after admission to a hospital in jeddah, saudi arabia. the aetiological agent was eventually identified as a coronavirus and designated middle east respiratory syndrome coronavirus (mers-cov). mers-cov has now been reported in mo ...201829495250
recent advances in aiv biosensors composed of nanobio hybrid material.since the beginning of the 2000s, globalization has accelerated because of the development of transportation systems that allow for human and material exchanges throughout the world. however, this globalization has brought with it the rise of various pathogenic viral agents, such as middle east respiratory syndrome coronavirus (mers-cov), severe acute respiratory syndrome coronavirus (sars-cov), zika virus, and dengue virus. in particular, avian influenza virus (aiv) is highly infectious and cau ...201830544883
adaptive evolution of mers-cov to species variation in dpp4.middle east respiratory syndrome coronavirus (mers-cov) likely originated in bats and passed to humans through dromedary camels; however, the genetic mechanisms underlying cross-species adaptation remain poorly understood. variation in the host receptor, dipeptidyl peptidase 4 (dpp4), can block the interaction with the mers-cov spike protein and form a species barrier to infection. to better understand the species adaptability of mers-cov, we identified a suboptimal species-derived variant of dp ...201830110630
a systematic review of therapeutic agents for the treatment of the middle east respiratory syndrome coronavirus (mers-cov).the middle east respiratory syndrome coronavirus (mers-cov) was first described in 2012 and attracted a great international attention due to multiple healthcare associated outbreaks. the disease carries a high case fatality rate of 34.5%, and there is no internationally or nationally recommended therapy.202031252170
[advances in the animal models of mers-cov].the middle east respiratory syndrome coronavirus (mers-cov) was first isolated in 2012 from patients that died from severe pneumonia. it was another coronavirus which resulted in severe infection of humans, apart from the severe acute respiratory syndrome coronavirus. the development of an appropriate animal model is necessary to study the pathogenesis and to evaluate the intervening measures against mers-cov infection. to date, several small animals(e.g., mice, syrian hamsters, and ferrets) hav ...201629963837
a spike-modified middle east respiratory syndrome coronavirus (mers-cov) infectious clone elicits mild respiratory disease in infected rhesus macaques.the recurrence of new human cases of middle east respiratory syndrome coronavirus (mers-cov) underscores the need for effective therapeutic countermeasures. nonhuman primate models are considered the gold standard for preclinical evaluation of therapeutic countermeasures. however, mers-cov-induced severe respiratory disease in humans is associated with high viral loads in the lower respiratory tract, which may be difficult to achieve in nonhuman primate models. considering this limitation, we wa ...201830013082
effects of the severe acute respiratory syndrome coronavirus (sars-cov) and the middle east respiratory syndrome coronavirus (mers-cov) on the nervous system. what can we expect from sars -cov-2?coronaviruses cause respiratory and gastrointestinal disorders in animals and humans. the current sars-cov-2, the covid-19 infectious agent, belongs to a subgroup called betacoronavirus including the sars-cov and mers-cov responsible for epidemics in 2002 and 2012, respectively.these viruses can also infect the nervous system due to their affinity for the human angiotensin-converting enzyme 2 (ace2) expressed in neurons and glial cells. infections with sars-cov, mers-cov, and now sars-cov-2 also ...202033152201
middle east respiratory syndrome coronavirus gene 5 modulates pathogenesis in mice.middle east respiratory syndrome coronavirus (mers-cov) causes a highly lethal pneumonia that emerged in 2012. there is limited information on mers-cov pathogenesis, as data from patients are scarce and the generation of animal models reproducing mers clinical manifestations has been challenging. human dipeptidyl peptidase 4 knock-in (hdpp4-ki) mice and a mouse-adapted mers-cov (mersma-6-1-2) were recently described. hdpp4-ki mice infected with mersma-6-1-2 show pathological signs of respiratory ...202033144319
utility of proteomics in emerging and re-emerging infectious diseases caused by rna viruses.emerging and re-emerging infectious diseases due to rna viruses cause major negative consequences for the quality of life, public health, and overall economic development. most of the rna viruses causing illnesses in humans are of zoonotic origin. zoonotic viruses can directly be transferred from animals to humans through adaptation, followed by human-to-human transmission, such as in human immunodeficiency virus (hiv), severe acute respiratory syndrome coronavirus (sars-cov), middle east respir ...202033095583
neutralizing and binding activities against sars-cov-1/2, mers-cov, and human coronaviruses 229e and oc43 by normal human intravenous immunoglobulin derived from healthy donors in japan.there are several types of coronaviruses that infect humans and cause disease. the latest is severe acute respiratory syndrome coronavirus 2 (sars-cov-2), which is an emerging global threat with no current effective treatment. normal intravenous immunoglobulin (n-ivig) has been administered to coronavirus disease 2019 (covid-19) patients to control severe inflammation and the cellular immune response. however, the neutralizing activity of n-ivig against sars-cov-2 has not yet been fully evaluate ...202033104267
molecular diversity of coronavirus host cell entry receptors.coronaviruses are a group of viruses causing disease in a wide range of animals including humans. since 2002, the successive emergence of bat-borne severe acute respiratory syndrome coronavirus (sars-cov), middle east respiratory syndrome coronavirus (mers-cov), swine acute diarrhea syndrome coronavirus (sads-cov) and sars-cov-2 have reinforced efforts in uncovering the molecular and evolutionary mechanisms governing coronavirus cell tropism and interspecies transmission. decades of studies have ...202033118022
anti-s1 mers-cov igy specific antibodies decreases lung inflammation and viral antigen positive cells in the human transgenic mouse model.the middle east respiratory syndrome coronavirus (mers-cov) was identified in 2012 and causes severe and often fatal acute respiratory illness in humans. no approved prophylactic and therapeutic interventions are currently available. in this study, we have developed egg yolk antibodies (immunoglobulin y (igy)) specific for mers-cov spike protein (s1) in order to evaluate their neutralizing efficiency against mers-cov infection. s1-specific immunoglobulins were produced by injecting chickens with ...202033139631
inhibition of coronavirus entry in vitro and ex vivo by a lipid-conjugated peptide derived from the sars-cov-2 spike glycoprotein hrc domain.the emergence of severe acute respiratory syndrome coronavirus type 2 (sars-cov-2), the etiological agent of the 2019 coronavirus disease (covid-19), has erupted into a global pandemic that has led to tens of millions of infections and hundreds of thousands of deaths worldwide. the development of therapeutics to treat infection or as prophylactics to halt viral transmission and spread is urgently needed. sars-cov-2 relies on structural rearrangements within a spike (s) glycoprotein to mediate fu ...202033082259
immunosuppressive drugs and covid-19: a review.coronavirus disease 2019 (covid-19) is caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2). it is currently unknown whether immunosuppressive drugs are advantageous or detrimental in patients with covid-19. immunosuppressive drugs could be harmful in the initial phase of covid-19. in this phase, the host immune response is necessary to inhibit viral replication. however, immunosuppressive drugs might have a beneficial effect in the later, more severe phase of covid-19. in this ...202032982743
update of the current knowledge on genetics, evolution, immunopathogenesis, and transmission for coronavirus disease 19 (covid-19).in december 2019, an acute respiratory disease caused by novel species of coronavirus (sars-cov-2), emerged in china and has spread throughout the world. on 11th march 2020, the world health organization (who) officially declared coronavirus disease 19 (covid-19) a pandemic, severe coronavirus-mediated human disease. based on genomic and phylogenetic studies, sars-cov-2 might originate from bat coronaviruses and infects humans directly or through intermediate zoonotic hosts. however, the exact o ...202033061805
immunopathogenesis of coronavirus-induced acute respiratory distress syndrome (ards): potential infection-associated hemophagocytic lymphohistiocytosis.the outbreak of coronavirus disease 2019 (covid-19) in december 2019 in wuhan, china, introduced the third highly pathogenic coronavirus into humans in the 21st century. scientific advance after the severe acute respiratory syndrome coronavirus (sars-cov) epidemic and middle east respiratory syndrome coronavirus (mers-cov) emergence enabled clinicians to understand the epidemiology and pathophysiology of sars-cov-2. in this review, we summarize and discuss the epidemiology, clinical features, an ...202033055229
the middle east respiratory syndrome coronavirus in the breath of some infected dromedary camels (camelus dromedarius).dromedary camels remain the currently identified reservoir for the middle east respiratory syndrome coronavirus (mers-cov). the virus is released in the secretions of the infected camels, especially the nasal tract. the virus shedding curve through the nasal secretions was studied. although human transmission of the virus through the respiratory tract of close contact people with dromedary reported previously, the exact mechanism of transmission is still largely unknown. the main goal of this st ...202033050973
middle east respiratory coronavirus (mers-cov) spike (s) protein vesicular stomatitis virus pseudoparticle neutralization assays offer a reliable alternative to the conventional neutralization assay in human seroepidemiological studies.middle east respiratory syndrome coronavirus (mers-cov) is a novel zoonotic coronavirus that was identified in 2012. mers-cov infection in humans can result in an acute, severe respiratory disease and in some cases multi-organ failure; the global mortality rate is approximately 35 %. the mers-cov spike (s) protein is a major target for neutralizing antibodies in infected patients. the mers-cov microneutralization test (mnt) is the gold standard method for demonstrating prior infection. however, ...201932974558
coronavirus infections in children: from sars and mers to covid-19, a narrative review of epidemiological and clinical features.emerging and re-emerging viruses represent an important challenge for global public health. in the 1960s, coronaviruses (covs) were recognized as disease agents in humans. in only two decades, three strains of covs have crossed species barriers rapidly emerging as human pathogens resulting in life-threatening disease with a pandemic potential: severe acute respiratory syndrome coronavirus (sars-cov) in 2002, middle-east respiratory syndrome coronavirus (mers-cov) in 2012 and the recently emerged ...202032921726
targeting polyamines inhibits coronavirus infection by reducing cellular attachment and entry.coronaviruses first garnered widespread attention in 2002 when the severe acute respiratory syndrome coronavirus (sars-cov) emerged from bats in china and rapidly spread in human populations. since then, middle east respiratory syndrome coronavirus (mers-cov) emerged and still actively infects humans. the recent sars-cov-2 outbreak and the resulting disease (coronavirus disease 2019, covid19) have rapidly and catastrophically spread and highlighted significant limitations to our ability to contr ...202032966040
stability of mers-cov rna on spin columns of rna extraction kit at room temperature.middle east respiratory syndrome coronavirus (mers-cov) is an emerging virus causing a highly fatal respiratory disease in humans. confirmation of mers-cov infection and molecular study on the virus may require transportation of samples to specialized laboratories. while freezing at -80 °c is the gold standard method for rna preservation, maintaining the integrity of viral rna during transport will require additional precautions and, as a result, increase transport costs. we aimed at testing the ...202032947111
molecular basis of pathogenesis of coronaviruses: a comparative genomics approach to planetary health to prevent zoonotic outbreaks in the 21st century.in the first quarter of the 21st century, we are already facing the third emergence of a coronavirus outbreak, the severe acute respiratory syndrome coronavirus 2 (sars-cov-2) responsible for the coronavirus disease 2019 (covid-19) pandemic. comparative genomics can inform a deeper understanding of the pathogenesis of covid-19. previous strains of coronavirus, sars-cov, and middle-east respiratory syndrome-coronavirus (mers-cov), have been known to cause acute lung injuries in humans. sars-cov-2 ...202032940573
structural basis of sars-cov-2 main protease inhibition by a broad-spectrum anti-coronaviral drug.the coronavirus disease 2019 (covid-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2) or 2019 novel coronavirus (2019-ncov), took tens of thousands of lives and caused tremendous economic losses. the main protease (mpro) of sars-cov-2 is a potential target for treatment of covid-19 due to its critical role in maturation of viral proteins and subsequent viral replication. conceptually and technically, targeting therapy against mpro is similar to target therapy t ...202032905393
in silico structure modelling of sars-cov-2 nsp13 helicase and nsp14 and repurposing of fda approved antiviral drugs as dual inhibitors.the high mortality rate from the severe acute respiratory syndrome coronavirus 2 (sars-cov-2) infections in humans and the lack of effective therapeutic regime for its treatment necessitates the identification of new antivirals. sars-cov-2 relies on non-structural proteins such as nsp13 helicase and nsp14 which are the key components of the replication-transcription complex (rtc) to complete its infectious life cycle. therefore, targeting these essential viral proteins with small molecules will ...202032875166
predicting the recombination potential of severe acute respiratory syndrome coronavirus 2 and middle east respiratory syndrome coronavirus.severe acute respiratory syndrome coronavirus 2 (sars-cov-2) recently emerged to cause widespread infections in humans. sars-cov-2 infections have been reported in the kingdom of saudi arabia, where middle east respiratory syndrome coronavirus (mers-cov) causes seasonal outbreaks with a case fatality rate of ~37 %. here we show that there exists a theoretical possibility of future recombination events between sars-cov-2 and mers-cov rna. through computational analyses, we have identified homolog ...202032902372
current state of vaccine development and targeted therapies for covid-19: impact of basic science discoveries.coronavirus disease-19 (covid-19) is caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2). sars-cov-2 is closely related to two other coronaviruses that caused disease epidemic breakouts in humans in the last 2 decades, namely, severe acute respiratory distress syndrome coronavirus (sars-cov) and middle east respiratory syndrome coronavirus (mers-cov). the similarities have enabled the scientists to apply the basic scientific discoveries garnered from studying the structure and ...202032889088
coronaviruses and endocrine system: a systematic review on evidences and shadows.coronaviruses are a big family of viruses that can infect mammalians and birds. in humans they mainly cause respiratory tract infections, with a large spectrum of severity, from mild, self-limited infections to highly lethal forms as severe acute respiratory syndrome coronavirus (sars-cov), middle east respiratory syndrome coronavirus (mers-cov) and coronavirus disease 2019 (covid-19). scanty data are reported for the involvement of endocrine glands by human coronaviruses, in particular sars-cov ...202032888287
an overview of middle east respiratory syndrome coronavirus vaccines in preclinical studies.middle east respiratory syndrome coronavirus (mers-cov) causes high mortality in humans. no vaccines are approved for use in humans; therefore, a consistent effort to develop safe and effective mers vaccines is needed.202032842811
covid-19 vaccines: a race against time in the middle of death and devastation!the coronavirus disease 2019 (covid-19) has turned into a global human tragedy and economic devastation. governments have implemented lockdown measures, blocked international travel, and enforced other public containment measures to mitigate the virus morbidity and mortality. as of today, no drug has the power to fight the infection and bring normalcy to the utter chaos. this leaves us with only one choice namely an effective and safe vaccine that shall be manufactured as soon as possible and av ...202032837093
antiviral potential of garlic (allium sativum) and its organosulfur compounds: a systematic update of pre-clinical and clinical data.garlic (allium sativum l.) is a common herb consumed worldwide as functional food and traditional remedy for the prevention of infectious diseases since ancient time. garlic and its active organosulfur compounds (oscs) have been reported to alleviate a number of viral infections in pre-clinical and clinical investigations. however, so far no systematic review on its antiviral effects and the underlying molecular mechanisms exists.202032836826
severe acute respiratory syndrome coronavirus-2 (sars-cov-2), a newly emerged pathogen: an overview.coronavirus disease 2019 (covid-19) is a viral pneumonia, responsible for the recent pandemic, and originated from wuhan, china, in december 2019. the causative agent of the outbreak was identified as coronavirus and designated as severe acute respiratory syndrome coronavirus 2 (sars- cov-2). few years back, the severe acute respiratory syndrome coronavirus (sars- cov) and the middle east respiratory syndrome coronavirus (mers-cov) were reported to be highly pathogenic and caused severe infectio ...202032840560
approach to childhood asthma in the era of covid-19: the official statement endorsed by the saudi pediatric pulmonology association (sppa).coronaviruses are a large family of viruses that infect humans, which may result in mild symptoms similar to those of the common cold. covid-19 is most recent subtype similar or even worse than the two previous pandemic strains which were the severe acute respiratory syndrome coronavirus (sars-cov) and the middle east respiratory syndrome coronavirus (mers-cov). the first cases of covid-19 emerged in december 2019. since then, the virus causing the disease has infected more than four million peo ...202032838011
structure-based virtual screening of phytochemicals and repurposing of fda approved antiviral drugs unravels lead molecules as potential inhibitors of coronavirus 3c-like protease enzyme.coronaviruses are enveloped positive-strand rna viruses belonging to family coronaviridae and order nidovirales which cause infections in birds and mammals. among the human coronaviruses, highly pathogenic ones are severe acute respiratory syndrome coronavirus (sars-cov) and the middle east respiratory syndrome coronavirus (mers-cov) which have been implicated in severe respiratory syndrome in humans. there are no approved antiviral drugs or vaccines for the treatment of human cov infection to d ...202032837113
neurological manifestations of covid-19 and other coronaviruses: a systematic review.to describe the main neurological manifestations related to coronavirus infection in humans.202032834527
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