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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
two novel dromedary camel bocaparvoviruses from dromedaries in the middle east with unique genomic features.the recent emergence of middle east respiratory syndrome (mers) coronavirus and its discovery from dromedary camels has boosted interest in the search for novel viruses in dromedaries. while bocaparvoviruses are known to infect various animals, it was not known that they exist in dromedaries. in this study, we describe the discovery of two novel dromedary camel bocaparvoviruses (dbovs), dbov1 and dbov2, from dromedary faecal samples in dubai. among 667 adult dromedaries and 72 dromedary calves, ...201728613145
estimation of basic reproduction number of the middle east respiratory syndrome coronavirus (mers-cov) during the outbreak in south korea, 2015.in south korea, an outbreak of middle east respiratory syndrome (mers) occurred in 2015. it was the second largest mers outbreak. as a result of the outbreak in south korea, 186 infections were reported, and 36 patients died. at least 16,693 people were isolated with suspicious symptoms. this paper estimates the basic reproduction number of the mers coronavirus (cov), using data on the spread of mers in south korea.201728610609
computational modeling of the bat hku4 coronavirus 3cl(pro) inhibitors as a tool for the development of antivirals against the emerging middle east respiratory syndrome (mers) coronavirus.the middle east respiratory syndrome coronavirus (mers-cov) is an emerging virus that poses a major challenge to clinical management. the 3c-like protease (3cl(pro) ) is essential for viral replication and thus represents a potential target for antiviral drug development. presently, very few data are available on mers-cov 3cl(pro) inhibition by small molecules. we conducted extensive exploration of the pharmacophoric space of a recently identified set of peptidomimetic inhibitors of the bat hku4 ...201728608547
comparative epidemiology of middle east respiratory syndrome coronavirus (mers-cov) in saudi arabia and south korea.mers-cov infection emerged in the kingdom of saudi arabia (ksa) in 2012 and has spread to 26 countries. however, 80% of all cases have occurred in ksa. the largest outbreak outside ksa occurred in south korea (sk) in 2015. in this report, we describe an epidemiological comparison of the two outbreaks. data from 1299 cases in ksa (2012-2015) and 186 cases in sk (2015) were collected from publicly available resources, including flutrackers, the world health organization (who) outbreak news and the ...201728588290
mers-cov antibody responses 1 year after symptom onset, south korea, 2015.we investigated the kinetics of the middle east respiratory syndrome coronavirus (mers-cov) neutralizing and spike protein antibody titers over the course of 1 year in 11 patients who were confirmed by reverse transcription pcr to have been infected during the outbreak in south korea in 2015. robust antibody responses were detected in all survivors who had severe disease; responses remained detectable, albeit with some waning, for <1 year. the duration of viral rna detection (but not viral load) ...201728585916
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
rapid development of vaccines against emerging pathogens: the replication-deficient simian adenovirus platform technology.despite the fact that there had been multiple small outbreaks of ebola virus disease, when a large outbreak occurred in 2014 there were no vaccines or drugs available for use. clinical development of multiple candidate vaccines was then initiated in parallel with attempts to contain the outbreak but only one vaccine was eventually tested in a phase iii trial. in order to be better prepared for future outbreaks of known human pathogens, platform technologies to accelerate vaccine development shou ...201728576573
identified transmission dynamics of middle east respiratory syndrome coronavirus infection during an outbreak: implications of an overcrowded emergency department.a total 130 cases of middle east respiratory syndrome coronavirus were identified during a large hospital outbreak in saudi arabia; 87 patients and 43 healthcare workers. the majority (80%) of transmission was healthcare-acquired (hai) infection, with 4 generations of hai transmission. the emergency department was the main location of exposure.201728575307
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
to what extent are arab pilgrims to makkah aware of the middle east respiratory syndrome coronavirus and the precautions against it?approximately, 80% of the many cases of the middle east respiratory syndrome coronavirus (mers-cov) confirmed worldwide were diagnosed in the kingdom of saudi arabia (ksa). the risk of the disease spreading internationally is especially worrying given the role of ksa as the home of the most important islamic pilgrimage sites. this means the need to assess arab pilgrims' awareness of mers-cov is of paramount importance.201728566972
evaluation of a real-time reverse transcription-pcr (rt-pcr) assay for detection of middle east respiratory syndrome coronavirus (mers-cov) in clinical samples from an outbreak in south korea in 2015. 201728566313
atypical presentations of mers-cov infection in immunocompromised hosts.during the 2015 korean mers outbreak, we experienced atypical presentations of mers-cov infections in three immunocompromised hosts that warranted exceptional management. case 1 showed delayed symptom development after a four-day asymptomatic period, case 2 experienced a 20-day incubation period, and case 3 exhibited persistent viral shedding without clinical deterioration. recognizing these exceptions is extremely important in the management of mers-cov-exposed or -infected patients and for con ...201728545936
potent and selective inhibition of pathogenic viruses by engineered ubiquitin variants.the recent middle east respiratory syndrome coronavirus (mers-cov), ebola and zika virus outbreaks exemplify the continued threat of (re-)emerging viruses to human health, and our inability to rapidly develop effective therapeutic countermeasures. many viruses, including mers-cov and the crimean-congo hemorrhagic fever virus (cchfv) encode deubiquitinating (dub) enzymes that are critical for viral replication and pathogenicity. they bind and remove ubiquitin (ub) and interferon stimulated gene 1 ...201728542609
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
efficient reverse genetic systems for rapid genetic manipulation of emergent and preemergent infectious coronaviruses.emergent and preemergent coronaviruses (covs) pose a global threat that requires immediate intervention. rapid intervention necessitates the capacity to generate, grow, and genetically manipulate infectious covs in order to rapidly evaluate pathogenic mechanisms, host and tissue permissibility, and candidate antiviral therapeutic efficacy. covs encode the largest viral rna genomes at about 28-32,000 nucleotides in length, and thereby complicate efficient engineering of the genome. deconstructing ...201728508214
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
perception and attitude of emergency room resident physicians toward middle east respiratory syndrome outbreak.introduction. middle east respiratory syndrome (mers) outbreaks have had a considerable negative impact on health systems in saudi arabia. we aimed to study the psychological impact of a middle east respiratory syndrome coronavirus (mers-cov) outbreak on emergency room resident physicians (errps). methods. we assessed the mers-related psychological impact and concerns of errps using a self-report questionnaire. results. the majority (91%) of the errps agreed that their work put them at risk of i ...201728487774
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
zero transmission of middle east respiratory syndrome: lessons learned from thailand.new emerging pathogens can quickly become a global health threat in this era. a number of middle east respiratory syndrome (mers) outbreaks have been linked to healthcare facilities. the healthcare-associated transmission of middle east respiratory syndrome coronavirus (mers-cov) has been attributed to overcrowding, delayed diagnosis, and the breakdown of infection control systems. strict infection control precautions and a well-prepared hospital system may have contributed to no nosocomial tran ...201728475787
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
virucidal activity of world health organization-recommended formulations against enveloped viruses, including zika, ebola, and emerging coronaviruses.the world health organization (who) published 2 alcohol-based formulations to be used in healthcare settings and for outbreak-associated infections, but inactivation efficacies of these products have not been determined against (re-)emerging viruses. in this study, we evaluated the virucidal activity of these who products in a comparative analysis. zika virus (zikv), ebola virus (ebov), severe acute respiratory syndrome coronavirus (sars-cov), and middle east respiratory syndrome coronavirus (me ...201728453839
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
hematologic, hepatic, and renal function changes in hospitalized patients with middle east respiratory syndrome coronavirus.there are no longitudinal data on the changes in hematologic, hepatic, and renal function findings in patients with middle east respiratory syndrome coronavirus (mers-cov) infection.201728444873
infectivity of an asymptomatic patient with middle east respiratory syndrome coronavirus infection.during the mers outbreak in korea, one case of asymptomatic or mild mers-cov infection was noted. eighty-two persons were exposed to the case without protection. they were isolated and rt-pcr and serology for mers were performed. there was no transmission through an asymptomatic mers case in this study.201728444154
structural insights into the interaction of coronavirus papain-like proteases and interferon-stimulated gene product 15 from different species.severe acute respiratory syndrome coronavirus (sars-cov) and middle east respiratory syndrome coronavirus (mers-cov) encode multifunctional papain-like proteases (plps) that have the ability to process the viral polyprotein to facilitate rna replication and antagonize the host innate immune response. the latter function involves reversing the post-translational modification of cellular proteins conjugated with either ubiquitin (ub) or ub-like interferon-stimulated gene product 15 (isg15). ub is ...201728438633
research needed to prevent mers coronavirus outbreaks. 201728422017
two deletion variants of middle east respiratory syndrome coronavirus found in a patient with characteristic symptoms.significant sequence variation of middle east respiratory syndrome coronavirus (mers cov) has never been detected since it was first reported in 2012. a mers patient came from korea to china in late may 2015. the patient was 44 years old and had symptoms including high fever, dry cough with a little phlegm, and shortness of breath, which are roughly consistent with those associated with mers, and had had close contact with individuals with confirmed cases of mers.after one month of therapy with ...201728421366
synonymous and biased codon usage by mers cov papain-like and 3cl-proteases.middle east respiratory syndrome coronavirus (mers cov) is a recently evolved fatal respiratory disease that poses a concern for a global epidemic. mers cov encodes 2 proteases, 3c-like protease (3clpro) and papain-like protease (plpro). these proteases share in processing mers cov polyproteins at different sites to yield 16 nonstructural proteins. in this work, we provide evidence that mers cov 3clpro and plpro are subject to different genetic and evolutionary influences that shape the protein ...201728420819
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
comparison of eplex respiratory pathogen panel with laboratory-developed real-time pcr assays for detection of respiratory pathogens.infections of the respiratory tract can be caused by a diversity of pathogens, both viral and bacterial. rapid microbiological diagnosis ensures appropriate antimicrobial therapy as well as effective implementation of isolation precautions. the eplex respiratory pathogen panel (rp panel) is a novel molecular biology-based assay, developed by genmark diagnostics, inc. (carlsbad, ca), to be performed within a single cartridge for the diagnosis of 25 respiratory pathogens (viral and bacterial). the ...201728404682
middle east respiratory syndrome in children. dental considerations.as of january 2016, 1,633 laboratory-confirmed cases of middle east respiratory syndrome coronavirus (mers-cov) infection and 587 mers-related deaths have been reported by the world health organization globally. middle east respiratory syndrome coronavirus  may occur sporadically in communities or may be transmitted within families or hospitals. the number of confirmed mers-cov cases among healthcare workers has been increasing. middle east respiratory syndrome coronavirus may also spread throug ...201728397938
multiplex paper-based colorimetric dna sensor using pyrrolidinyl peptide nucleic acid-induced agnps aggregation for detecting mers-cov, mtb, and hpv oligonucleotides.the development of simple fluorescent and colorimetric assays that enable point-of-care dna and rna detection has been a topic of significant research because of the utility of such assays in resource limited settings. the most common motifs utilize hybridization to a complementary detection strand coupled with a sensitive reporter molecule. here, a paper-based colorimetric assay for dna detection based on pyrrolidinyl peptide nucleic acid (acpcpna)-induced nanoparticle aggregation is reported a ...201728394582
clinical and epidemiologic characteristics of spreaders of middle east respiratory syndrome coronavirus during the 2015 outbreak in korea.nosocomial transmission is an important characteristic of middle east respiratory syndrome coronavirus (mers-cov) infection. risk factors for transmission of mers-cov in healthcare settings are not well defined. during the korean outbreak in 2015, 186 patients had laboratory-confirmed mers-cov infection. those suspected as a source of viral transmission were categorized into the spreader groups (super-spreader [n = 5] and usual-spreader [n = 10]) and compared to the non-spreader group (n = 171). ...201728378546
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
effects of operational decisions on the diffusion of epidemic disease: a system dynamics modeling of the mers-cov outbreak in south korea.we evaluated the nosocomial outbreak of middle east respiratory syndrome (mers) coronavirus (cov) in the republic of korea, 2015, from a healthcare operations management perspective. establishment of healthcare policy in south korea provides patients' freedom to select and visit multiple hospitals. current policy enforces hospitals preference for multi-patient rooms to single-patient rooms, to lower financial burden. existing healthcare systems tragically contributed to 186 mers outbreak cases, ...201728351702
mouse-adapted mers coronavirus causes lethal lung disease in human dpp4 knockin mice.the middle east respiratory syndrome (mers) emerged in saudi arabia in 2012, caused by a zoonotically transmitted coronavirus (cov). over 1,900 cases have been reported to date, with ∼36% fatality rate. lack of autopsies from mers cases has hindered understanding of mers-cov pathogenesis. a small animal model that develops progressive pulmonary manifestations when infected with mers-cov would advance the field. as mice are restricted to infection at the level of dpp4, the mers-cov receptor, we g ...201728348219
surveillance and testing for middle east respiratory syndrome coronavirus, saudi arabia, april 2015-february 2016.saudi arabia has reported >80% of the middle east respiratory syndrome coronavirus (mers-cov) cases worldwide. during april 2015-february 2016, saudi arabia identified and tested 57,363 persons (18.4/10,000 residents) with suspected mers-cov infection; 384 (0.7%) tested positive. robust, extensive, and timely surveillance is critical for limiting virus transmission.201728322710
domestic pig unlikely reservoir for mers-cov.we tested the suitability of the domestic pig as a model for middle east respiratory syndrome coronavirus (mers-cov) infection. inoculation did not cause disease, but a low level of virus replication, shedding, and seroconversion were observed. pigs do not recapitulate human mers-cov and are unlikely to constitute a reservoir in nature.201728318484
dna vaccine encoding middle east respiratory syndrome coronavirus s1 protein induces protective immune responses in mice.the middle east respiratory syndrome coronavirus (mers-cov), is an emerging pathogen that continues to cause outbreaks in the arabian peninsula and in travelers from this region, raising the concern that a global pandemic could occur. here, we show that a dna vaccine encoding the first 725 amino acids (s1) of mers-cov spike (s) protein induces antigen-specific humoral and cellular immune responses in mice. with three immunizations, high titers of neutralizing antibodies (up to 1: 10(4)) were gen ...201728314561
receptor-binding domain of mers-cov with optimal immunogen dosage and immunization interval protects human transgenic mice from mers-cov infection.middle east respiratory syndrome (mers) continues to raise worldwide concerns due to its pandemic potential. increased mers cases and no licensed mers vaccines highlight the need to develop safe and effective vaccines against mers. we have previously demonstrated that a receptor-binding domain (rbd) fragment containing residues 377-588 of mers-coronavirus (mers-cov) spike protein is a critical neutralizing domain and an important vaccine target. nevertheless, its optimal immunogen dosage and imm ...201728277821
molecular dynamic studies of interferon and innate immunity resistance in mers cov non-structural protein 3.the new emerging middle east respiratory syndrome coronavirus (mers cov) encodes several resistance proteins against the innate immune response of the host, including interferon (ifn) resistance. monitoring of the status of such proteins will be important to track viral pathogenicity. in this study, molecular dynamics approaches were used to investigate mers cov non-structural protein 3 (nsp3) specific proteins that resist host innate immunity. mers cov papain-like protease (plpro) was more conf ...201728250277
mers-cov spike nanoparticles protect mice from mers-cov infection.the middle east respiratory syndrome coronavirus (mers-cov) was first discovered in late 2012 and has gone on to cause over 1800 infections and 650 deaths. there are currently no approved therapeutics or vaccinations for mers-cov. the mers-cov spike (s) protein is responsible for receptor binding and virion entry to cells, is immunodominant and induces neutralizing antibodies in vivo, all of which, make the s protein an ideal target for anti-mers-cov vaccines. in this study, we demonstrate prote ...201728237499
acute respiratory infections among returning hajj pilgrims-jordan, 2014.the emergence of middle east respiratory syndrome coronavirus (mers-cov) has prompted enhanced surveillance for respiratory infections among pilgrims returning from the hajj, one of the largest annual mass gatherings in the world.201728226273
high fatality rates and associated factors in two hospital outbreaks of mers in daejeon, the republic of korea.to explore the epidemiological and clinical factors predictive of the case fatality rate (cfr) of middle east respiratory syndrome-coronavirus (mers-cov) infection in an outbreak in daejeon, the republic of korea.201728223175
identification and evaluation of potent middle east respiratory syndrome coronavirus (mers-cov) 3cl(pro) inhibitors.middle east respiratory syndrome coronavirus (mers-cov) causes severe acute respiratory illness with fever, cough and shortness of breath. up to date, it has resulted in 1826 human infections, including 649 deaths. analogous to picornavirus 3c protease (3c(pro)), 3c-like protease (3cl(pro)) is critical for initiation of the mers-cov replication cycle and is thus regarded as a validated drug target. as presented here, our peptidomimetic inhibitors of enterovirus 3c(pro) (6b, 6c and 6d) inhibited ...201728216367
middle east respiratory syndrome (mers) coronavirus: putting one health principles into practice? 201728216233
"your health essential for your hajj": muslim pilgrims' knowledge, attitudes and practices regarding middle east respiratory syndrome coronavirus (mers-cov) during hajj season.up to date, there have been no studies to evaluate pilgrims' knowledge, attitude and practices regarding mers-cov during the annual hajj pilgrimage in order to see whether there is a need for these aspects to be improved.201728216182
questionnaire-based analysis of infection prevention and control in healthcare facilities in saudi arabia in regards to middle east respiratory syndrome.effective implementation of infection prevention and control in healthcare facilities depends on training, awareness and compliance of healthcare workers. in saudi arabia recent significant hospital outbreaks, including middle east respiratory syndrome coronavirus (mers-cov), have resulted from lack of, or breakdown in, infection prevention and control procedures. this study was designed to assess attitudes to, and awareness of, infection prevention and control policies and guidelines among heal ...201728215912
epigenetic landscape during coronavirus infection.coronaviruses (cov) comprise a large group of emerging human and animal pathogens, including the highly pathogenic severe acute respiratory syndrome coronavirus (sars-cov) and middle east respiratory syndrome coronavirus (mers-cov) strains. the molecular mechanisms regulating emerging coronavirus pathogenesis are complex and include virus-host interactions associated with entry, replication, egress and innate immune control. epigenetics research investigates the genetic and non-genetic factors t ...201728212305
effective inhibition of mers-cov infection by resveratrol.middle east respiratory syndrome coronavirus (mers-cov) is an emerging viral pathogen that causes severe morbidity and mortality. up to date, there is no approved or licensed vaccine or antiviral medicines can be used to treat mers-cov-infected patients. here, we analyzed the antiviral activities of resveratrol, a natural compound found in grape seeds and skin and in red wine, against mers-cov infection.201728193191
resource impact of managing suspected middle east respiratory syndrome patients in a uk teaching hospital.clinical challenges exist in the management of hospitalized patients returning to the uk with potential middle east respiratory syndrome coronavirus (mers-cov) infection, particularly with its clinical overlap with influenza, as demonstrated in this case-series and cost-analysis review of returning hajj pilgrims. these patients were hospitalized with acute febrile respiratory illness, initially managed as potential mers-cov infections, but were eventually diagnosed with influenza. additional cos ...201728131646
progress of middle east respiratory syndrome coronavirus vaccines: a patent review.middle east respiratory syndrome coronavirus (mers-cov) has emerged as a new pathogen, causing severe complications and a high case fatality rate. no direct treatments are available as yet, highlighting the importance of prevention through suitable vaccination regimes. the viral spike (s) protein has been characterized as a key target antigen for vaccines. in particular, s protein domains have been utilized to produce high titers of neutralizing antibodies. areas covered: since the first report ...201728121202
clinical validation of 3 commercial real-time reverse transcriptase polymerase chain reaction assays for the detection of middle east respiratory syndrome coronavirus from upper respiratory tract specimens.since discovery of middle east respiratory syndrome coronavirus (mers-cov), a novel betacoronavirus first isolated and characterized in 2012, mers-cov real-time reverse transcriptase polymerase chain reaction (rrt-pcr) assays represent one of the most rapidly expanding commercial tests. however, in the absence of extensive evaluations of these assays on positive clinical material of different sources, evaluating their diagnostic effectiveness remains challenging. we describe the diagnostic perfo ...201728104327
case characteristics among middle east respiratory syndrome coronavirus outbreak and non-outbreak cases in saudi arabia from 2012 to 2015.as of 1 november 2015, the saudi ministry of health had reported 1273 cases of middle east respiratory syndrome (mers); among these cases, which included 9 outbreaks at several hospitals, 717 (56%) patients recovered, 14 (1%) remain hospitalised and 543 (43%) died. this study aimed to determine the epidemiological, demographic and clinical characteristics that distinguished cases of mers contracted during outbreaks from those contracted sporadically (ie, non-outbreak) between 2012 and 2015 in sa ...201728082362
x-ray structure and enzymatic activity profile of a core papain-like protease of mers coronavirus with utility for structure-based drug design.ubiquitin-like domain 2 (ubl2) is immediately adjacent to the n-terminus of the papain-like protease (plpro) domain in coronavirus polyproteins, and it may play a critical role in protease regulation and stability as well as in viral infection. however, our recent cellular studies reveal that removing the ubl2 domain from mers plpro has no effect on its ability to process the viral polyprotein or act as an interferon antagonist, which involves deubiquitinating and deisgylating cellular proteins. ...201728079137
middle east respiratory syndrome coronavirus (mers-cov) infection.middle east respiratory syndrome coronavirus was first described in 2012. more than 1800 cases have been reported so far, the majority from countries in the middle east region. this article outlines current understanding of the epidemiological and clinical features of middle east respiratory syndrome coronavirus infection.201728067571
an assessment of the level of concern among hospital-based health-care workers regarding mers outbreaks in saudi arabia.middle east respiratory syndrome (mers) is caused by mers coronavirus (mers-cov). more than 80% of reported cases have occurred in saudi arabia, with a mortality exceeding 50%. health-care workers (hcws) are at risk of acquiring and transmitting this virus, so the concerns of hcws in saudi arabia regarding mers were evaluated.201728049440
binding of the methyl donor s-adenosyl-l-methionine to middle east respiratory syndrome coronavirus 2'-o-methyltransferase nsp16 promotes recruitment of the allosteric activator nsp10.the middle east respiratory syndrome coronavirus (mers-cov) nonstructural protein 16 (nsp16) is an s-adenosyl-l-methionine (sam)-dependent 2'-o-methyltransferase (2'-o-mtase) that is thought to methylate the ribose 2'-oh of the first transcribed nucleotide (n1) of viral rna cap structures. this 2'-o-mtase activity is regulated by nsp10. the 2'-o methylation prevents virus detection by cell innate immunity mechanisms and viral translation inhibition by the interferon-stimulated ifit-1 protein. to ...201728031370
delayed management of staphyloccocus aureus infective endocarditis in a middle east respiratory syndrome coronavirus possible case hospitalized in 2015 in paris, france. 201727986520
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
risk factors for transmission of middle east respiratory syndrome coronavirus infection during the 2015 outbreak in south korea.transmission heterogeneity was observed during the 2015 south korean outbreak of middle east respiratory syndrome coronavirus (mers-cov) infection. only 22 of 186 cases transmitted the infection, and 5 super-spreading events caused 150 transmissions. we investigated the risk factors for mers-cov transmission.201727940937
update on therapeutic options for middle east respiratory syndrome coronavirus (mers-cov).the middle east respiratory syndrome coronavirus (mers-cov) is an important emerging respiratory pathogen. mers-cov resulted in multiple hospital outbreaks within and outside the arabian peninsula. the disease has a high case fatality rate, with the need for a therapeutic option. areas covered: in this review, we provide an overview of the progress in the development of therapeutic strategies for mers. we searched pubmed, embase, cochrane, scopus, and google scholar, using the following terms: ' ...201727937060
mers-cov spike protein: a key target for antivirals.the continual middle east respiratory syndrome (mers) threat highlights the importance of developing effective antiviral therapeutics to prevent and treat mers coronavirus (mers-cov) infection. a surface spike (s) protein guides mers-cov entry into host cells by binding to cellular receptor dipeptidyl peptidase-4 (dpp4), followed by fusion between virus and host cell membranes. mers-cov s protein represents a key target for developing therapeutics to block viral entry and inhibit membrane fusion ...201727936982
middle east respiratory syndrome coronavirus (mers-cov) outbreak in south korea, 2015: epidemiology, characteristics and public health implications.since the first case of middle east respiratory syndrome coronavirus (mers-cov) in south korea was reported on 20(th) may 2015, there have been 186 confirmed cases, 38 deaths and 16,752 suspected cases. previously published research on south korea's mers outbreak was limited to the early stages, when few data were available. now that the outbreak has ended, albeit unofficially, a more comprehensive review is appropriate.201728153558
differential cell count and crp level in blood as predictors for middle east respiratory syndrome coronavirus infection in acute febrile patients during nosocomial outbreak.a case-control study was performed to identify clinical predictors for middle east respiratory syndrome coronavirus (mers-cov) infection among patients with acute febrile illness during the nosocomial outbreak. patients with mers-cov were more likely to have monocytosis with normal white blood cell (wbc) count and lower c-reactive protein (crp) level. simple laboratory data such as complete blood counts (cbc) with differential count could be a useful marker for the prediction of mers and triage ...201727914145
protective t cell responses featured by concordant recognition of middle east respiratory syndrome coronavirus-derived cd8+ t cell epitopes and host mhc.the coordinated recognition of virus-derived t cell epitopes and mhc molecules by t cells plays a pivotal role in cellular immunity-mediated virus clearance. it has been demonstrated that the conformation of mhc class i (mhc i) molecules can be adjusted by the presented peptide, which impacts t cell activation. however, it is still largely unknown whether the conformational shift of mhc i influences the protective effect of virus-specific t cells. in this study, utilizing the middle east respira ...201727903740
the recombinant n-terminal domain of spike proteins is a potential vaccine against middle east respiratory syndrome coronavirus (mers-cov) infection.the persistent public health threat of infection with the middle east respiratory syndrome coronavirus (mers-cov) highlights the need for an effective mers-cov vaccine. previous studies have focused mainly on the receptor-binding domain (rbd) on the spike protein of mers-cov. herein, we investigated the immunogenicity and protective potential of the recombinant n-terminal domain (rntd) of spike proteins as a vaccine candidate. balb/c mice vaccinated with 5 or 10μg of rntd protein demonstrated a ...201727899228
passive immunotherapy for middle east respiratory syndrome coronavirus infection with equine immunoglobulin or immunoglobulin fragments in a mouse model.middle east respiratory syndrome (mers) is a highly lethal pulmonary infection caused by a coronavirus (cov), mers-cov. with the continuing spread of mers-cov, prophylactic and therapeutic treatments are urgently needed. in this study, we prepared purified equine f(ab')2 from horses immunized with mers-cov virus-like particles (vlps) expressing mers-cov s, m and e proteins. both igg and f(ab')2 efficiently neutralized mers-cov replication in tissue culture. passive transfer of equine immune anti ...201727890674
middle east respiratory syndrome coronavirus and children. 201727872356
t-cell immunity of sars-cov: implications for vaccine development against mers-cov.over 12 years have elapsed since severe acute respiratory syndrome (sars) triggered the first global alert for coronavirus infections. virus transmission in humans was quickly halted by public health measures and human infections of sars coronavirus (sars-cov) have not been observed since. however, other coronaviruses still pose a continuous threat to human health, as exemplified by the recent emergence of middle east respiratory syndrome (mers) in humans. the work on sars-cov widens our knowled ...201727840203
alisporivir inhibits mers- and sars-coronavirus replication in cell culture, but not sars-coronavirus infection in a mouse model.currently, there is no registered treatment for infections with emerging zoonotic coronaviruses like sars- and mers-coronavirus. we here report that in cultured cells low-micromolar concentrations of alisporivir, a non-immunosuppressive cyclosporin a-analog, inhibit the replication of four different coronaviruses, including mers- and sars-coronavirus. ribavirin was found to further potentiate the antiviral effect of alisporivir in these cell culture-based infection models, but this combination t ...201727840112
mplex: a robust and universal protocol for single-sample integrative proteomic, metabolomic, and lipidomic analyses.integrative multi-omics analyses can empower more effective investigation and complete understanding of complex biological systems. despite recent advances in a range of omics analyses, multi-omic measurements of the same sample are still challenging and current methods have not been well evaluated in terms of reproducibility and broad applicability. here we adapted a solvent-based method, widely applied for extracting lipids and metabolites, to add proteomics to mass spectrometry-based multi-om ...201727822525
cd8+ t cells and macrophages regulate pathogenesis in a mouse model of middle east respiratory syndrome.middle east respiratory syndrome coronavirus (mers-cov) is an important emerging pathogen that was first described in 2012. while the cell surface receptor for mers-cov has been identified as dipeptidyl peptidase 4 (dpp4), the mouse dpp4 homologue does not allow virus entry into cells. therefore, development of mouse models of mers-cov has been hampered by the fact that mers-cov does not replicate in commonly available mouse strains. we have previously described a mouse model in which mdpp4 was ...201727795435
recombinant receptor-binding domains of multiple middle east respiratory syndrome coronaviruses (mers-covs) induce cross-neutralizing antibodies against divergent human and camel mers-covs and antibody escape mutants.middle east respiratory syndrome coronavirus (mers-cov) binds to cellular receptor dipeptidyl peptidase 4 (dpp4) via the spike (s) protein receptor-binding domain (rbd). the rbd contains critical neutralizing epitopes and serves as an important vaccine target. since rbd mutations occur in different mers-cov isolates and antibody escape mutants, cross-neutralization of divergent mers-cov strains by rbd-induced antibodies remains unknown. here, we constructed four recombinant rbd (rrbd) proteins w ...201727795425
risk assessment and laboratory investigation of respiratory illness in travellers returning to singapore 2012-2015: experience from the mers-cov surveillance programme.since the emergence of middle east respiratory syndrome coronavirus (mers-cov), singapore has enhanced its national surveillance system to detect the potential importation of this novel pathogen. using the guidelines from the singapore ministry of health, a suspect case was defined as a person with clinical signs and symptoms suggestive of pneumonia or severe respiratory infection with breathlessness, and with an epidemiological link to countries where mers-cov cases had been reported within the ...201727780489
middle east respiratory syndrome: emergence of a pathogenic human coronavirus.in 2012, a zoonotic coronavirus was identified as the causative agent of middle east respiratory syndrome and was named mers coronavirus (mers-cov). as of august 11, 2016, the virus has infected 1,791 patients, with a mortality rate of 35.6%. although mers-cov generally causes subclinical or mild disease, infection can result in serious outcomes, including acute respiratory distress syndrome and multi-organ failure in patients with comorbidities. the virus is endemic in camels in the arabian pen ...201727576010
association of human leukocyte antigen class ii alleles with severe middle east respiratory syndrome-coronavirus infection.middle east respiratory syndrome (mers) is a disease of the lower respiratory tract and is characterized by high mortality. it is caused by a beta coronavirus (cov) referred to as mers-cov. majority of mers-cov cases have been reported from saudi arabia.201727512511
assessment of the risk posed to singapore by the 2015 middle east respiratory syndrome outbreak in the republic of korea.to assess the public health risk to singapore posed by the middle east respiratory syndrome (mers) outbreak in the republic of korea in 2015.201727508087
are saudi medical students aware of middle east respiratory syndrome coronavirus during an outbreak?recently, an outbreak of mers-cov occurred in king abdulaziz medical city (kamc), riyadh. this outbreak contributed to the students at the king saud bin abdulaziz university for health sciences (ksau-hs) becoming more involved in promoting health awareness in their communities. this was a cross-sectional study that evaluated students in the clinical phase of medical school. the data were collected by an online questionnaire. the measurements were obtained using a researcher-administered and a se ...201727502524
tracing airline travelers for a public health investigation: middle east respiratory syndrome coronavirus (mers-cov) infection in the united states, 2014.cdc routinely conducts contact investigations involving travelers on commercial conveyances, such as aircrafts, cargo vessels, and cruise ships.201727453599
consise statement on the reporting of seroepidemiologic studies for influenza (roses-i statement): an extension of the strobe statement.population-based serologic studies are a vital tool for understanding the epidemiology of influenza and other respiratory viruses, including the early assessment of the transmissibility and severity of the 2009 influenza pandemic, and middle east respiratory syndrome coronavirus. however, interpretation of the results of serologic studies has been hampered by the diversity of approaches and the lack of standardized methods and reporting.201727417916
middle east respiratory syndrome coronavirus in al-madinah city, saudi arabia: demographic, clinical and survival data.middle east respiratory syndrome coronavirus (mers-cov), is an emerging virus respiratory infection. it has a high mortality rate and a wide spectrum of clinical features. this study describes the clinical characteristics and outcome of mers infected patients.201727302882
cross-sectional survey and surveillance for influenza viruses and mers-cov among egyptian pilgrims returning from hajj during 2012-2015.approximately 80 000 egyptians participate in hajj pilgrimage annually. the purpose of this study was to estimate influenza virus and mers-cov prevalence among egyptian pilgrims returning from hajj.201727603034
infections in symptomatic travelers returning from the arabian peninsula to france: a retrospective cross-sectional study. 201727185404
epidemiological and clinical characteristics of patients with middle east respiratory syndrome coronavirus in iran in 2014.the middle east respiratory syndrome coronavirus (mers-cov) was a great global concern in 2014. it has a wide range of manifestations that may differ in each area as well as high mortality. in this study, we report the epidemiological characteristics, history, clinical, and paraclinical information of all 5 patients from iran with laboratory-confirmed mers-cov. all patients were from kerman province. none of them had a history of travel, contact with animals, or consumption of camel milk product ...201727169943
patient characteristics infected with middle east respiratory syndrome coronavirus infection in a tertiary hospital.in april 2014, a surge in cases of middle east respiratory syndrome coronavirus (mers-cov) infection was seen in jeddah, saudi arabia. the aim of this study is to describe the demographic and clinical features, laboratory and radiological findings of mers-cov patients identified during this outbreak in a single tertiary hospital.201727168861
preventing healthcare-associated transmission of the middle east respiratory syndrome (mers): our achilles heel.middle east respiratory syndrome (mers) coronavirus is the most recent among the coronaviridae family to jump species and infect humans. major healthcare associated mers outbreaks have occurred in the middle east and korea that affected both patients and healthcare workers. these outbreaks were characterized by intra and inter-hospital spread and were exacerbated specifically by overcrowding, delayed diagnosis and appropriate use of personal protective equipment. recent experience with this viru ...201727158023
clinical spectrum of the middle east respiratory syndrome coronavirus (mers-cov). 201727140697
nitazoxanide, a new drug candidate for the treatment of middle east respiratory syndrome coronavirus.nitazoxanide is a broad-spectrum antiviral agent undergoing clinical development for treatment of influenza and other viral respiratory infections. nitazoxanide exhibits in vitro activity against middle east respiratory syndrome coronavirus (mers-cov) and other coronaviruses, inhibiting expression of the viral n protein. nitazoxanide also suppresses production of pro-inflammatory cytokines in peripheral blood mononuclear cells and suppresses interleukin 6 production in mice. having been used ext ...201727095301
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
proceedings of the middle east respiratory syndrome (mers) coronavirus research initiative workshop, september 9-10 2015 in riyadh, ksa. 201727036308
fatality risks for nosocomial outbreaks of middle east respiratory syndrome coronavirus in the middle east and south korea.middle east respiratory syndrome coronavirus (mers-cov) was first isolated in 2012. the largest known outbreak outside the middle east occurred in south korea in 2015. as of 29 june 2016, 1769 laboratory-confirmed cases (630 deaths; 35.6 % case fatality rate [cfr]) had been reported from 26 countries, particularly in the middle east. however, the cfr for hospital outbreaks was higher than that of family clusters in the middle east and korea. here, we compared the mortality rates for 51 nosocomia ...201727664026
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
correction: middle east respiratory syndrome coronavirus intra-host populations are characterized by numerous high frequency variants.[this corrects the article doi: 10.1371/journal.pone.0146251.].201727111439
is the saudi public aware of middle east respiratory syndrome?to limit the spread of middle east respiratory syndrome coronavirus (mers-cov) in saudi arabia, the ministry of health tried to raise public awareness using different public campaigns. we aimed to measure public awareness of mers in saudi arabia. a cross-sectional study was conducted between may and june 2014 using a newly designed arabic questionnaire that was distributed and completed online. we analyzed the response of 1149 respondents across saudi arabia. we found that 97% of the participant ...201726589657
cdc's early response to a novel viral disease, middle east respiratory syndrome coronavirus (mers-cov), september 2012-may 2014.the first ever case of middle east respiratory syndrome coronavirus (mers-cov) was reported in september 2012. this report describes the approaches taken by cdc, in collaboration with the world health organization (who) and other partners, to respond to this novel virus, and outlines the agency responses prior to the first case appearing in the united states in may 2014. during this time, cdc's response integrated multiple disciplines and was divided into three distinct phases: before, during, a ...201726345122
assessment of the awareness level of dental students toward middle east respiratory syndrome-coronavirus.infection prevention and control measures are critical to prevent the possible spread of middle east respiratory syndrome-coronavirus (mers-cov) in healthcare facilities. therefore, healthcare workers should be aware of all procedures concerning prevention of and protection from mers-cov.201726236674
re-emerging middle east respiratory syndrome coronavirus: the hibernating bat hypothesis. 201726229568
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