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spatial modelling of contribution of individual level risk factors for mortality from middle east respiratory syndrome coronavirus in the arabian peninsula.middle east respiratory syndrome coronavirus is a contagious respiratory pathogen that is contracted via close contact with an infected subject. transmission of the pathogen has occurred through animal-to-human contact at first followed by human-to-human contact within families and health care facilities.201728759623
neurological complications during treatment of middle east respiratory syndrome.middle east respiratory syndrome (mers) has a high mortality rate and pandemic potential. however, the neurological manifestations of mers have rarely been reported since it first emerged in 2012.201728748673
permissivity of dpp4 orthologs to mers-coronavirus is governed by glycosylation and other complex determinants.middle east respiratory syndrome coronavirus (mers-cov) utilizes dipeptidyl peptidase 4 (dpp4) as an entry receptor. while bat, camel, and human dpp4 support mers-cov infection, several dpp4 orthologs, including mouse, ferret, hamster, and guinea pig, do not. previous work revealed that glycosylation of mouse dpp4 plays a role in blocking mers-cov infection. here, we test whether glycosylation also acts as a determinant of permissivity for ferret, hamster, and guinea pig dpp4. we find that while ...201728747502
outbreak of middle east respiratory syndrome-coronavirus causes high fatality after cardiac operations.middle east respiratory syndrome-coronavirus (mers-cov) resembles a severe form of community-acquired pneumonia initially reported in saudi arabia in 2012. the mers-cov epidemic poses a big challenge because of its high mortality. in january 2015, a patient who was potentially incubating mers-cov arrived from the emergency department of another hospital and was admitted with acute coronary syndrome. this resulted in an outbreak in the cardiac surgery ward that caused the deaths of 5 of 6 patient ...201728734432
awareness among a saudi arabian university community of middle east respiratory syndrome coronavirus following an outbreak.this study aimed to measure the level of awareness of faculty members, staff and students in a female saudi arabian university community towards middle east respiratory syndrome coronvirus (mers-cov) following an outbreak. a self-administered questionnaire containing knowledge questions was distributed and completed by the 1541 participants. the overall knowledge score was 43.2%. it was only significantly higher in participants from the health colleges (50.6%). the majority (78.9%) of the respon ...201728730588
diagnostic delays in 537 symptomatic cases of middle east respiratory syndrome coronavirus infection in saudi arabia.although the literature indicates that patient delays in seeking medical support for middle east respiratory syndrome coronavirus (mers-cov) infections are associated with poor clinical outcomes, delays in the diagnosis itself remain poorly understood in these patients. this study aimed to determine the median time interval from symptom onset to a confirmed diagnosis and to identify the potential predictors of this interval in saudi arabian mers patients.201728728926
the use of xenosurveillance to detect human bacteria, parasites, and viruses in mosquito bloodmeals.infectious disease surveillance is hindered by several factors, including limited infrastructure and geographic isolation of many resource-poor regions. in addition, the complexities of sample acquisition, processing, and analysis, even in developed regions, can be rate limiting. therefore, new strategies to survey human populations for emerging pathogens are necessary. xenosurveillance is a method that utilizes mosquitoes as sampling devices to search for genetic signatures of pathogens in vert ...201728722623
no serologic evidence of middle east respiratory syndrome coronavirus infection among camel farmers exposed to highly seropositive camel herds: a household linked study, kenya, 2013.abstracthigh seroprevalence of middle east respiratory syndrome coronavirus (mers-cov) among camels has been reported in kenya and other countries in africa. to date, the only report of mers-cov seropositivity among humans in kenya is of two livestock keepers with no known contact with camels. we assessed whether persons exposed to seropositive camels at household level had serological evidence of infection. in 2013, 760 human and 879 camel sera were collected from 275 and 85 households respecti ...201728719257
impact of middle east respiratory syndrome outbreak on the use of emergency medical resources in febrile patients.outbreaks of transmissible respiratory infection are suspected to have significant effects on the health of pediatric and geriatric patients. the objective was to assess the impact of the middle east respiratory syndrome (mers) outbreak on the use of emergency resources.201728717779
the clinical and virological features of the first imported case causing mers-cov outbreak in south korea, 2015.in 2015, the largest outbreak of middle east respiratory syndrome coronavirus (mers-cov) infection outside the middle east occurred in south korea. we summarized the epidemiological, clinical, and laboratory findings of the first korean case of mers-cov and analyzed whole-genome sequences of mers-cov derived from the patient.201728709419
suggested new breakpoints of anti-mers-cov antibody elisa titers: performance analysis of serologic tests.to provide optimal cut-off values of anti-middle east respiratory syndrome coronavirus (mers-cov) serologic tests, we evaluated performance of elisa igg, elisa iga, ifa igm, and ifa igg using 138 serum samples of 49 mers-cov-infected patients and 219 serum samples of 219 rrt-pcr-negative mers-cov-exposed healthcare personnel and patients. the performance analysis was conducted for two different purposes: (1) prediction of neutralization activity in mers-cov-infected patients, and (2) epidemiolog ...201728695355
middle east respiratory syndrome coronavirus and pulmonary tuberculosis coinfection: implications for infection control.coinfection of middle east respiratory syndrome coronavirus (mers-cov) with tuberculosis (tb) has not been previously reported. here, we present 2 cases with both mers-cov and pulmonary tb. the first case was a 13-year-old patient who was admitted with a 2-month history of fever, weight loss, night sweats, and cough. the second patient was a 30-year-old female who had a 4-week history of cough associated with shortness of breath and weight loss of 2 kg. the 2 patients were diagnosed with pulmona ...201728683463
middle east respiratory syndrome clinical practice guideline for hemodialysis facilities.the korean society of nephrology participated in the task force team consisting of government authorities and civilian experts to prevent and control the spread of middle east respiratory syndrome (mers) in 2015. the korean society of nephrology mers task force team took an immediate action and drafted 'the clinical recommendation for hemodialysis facilities' to follow when the first and the only confirmed case was reported in the hemodialysis unit. owing to the dedicated support from medical do ...201728680819
middle east respiratory syndrome coronavirus experimental transmission using a pig model.dromedary camels are the main reservoir of middle east respiratory syndrome coronavirus (mers-cov), but other livestock species (i.e., alpacas, llamas, and pigs) are also susceptible to infection with mers-cov. animal-to-animal transmission in alpacas was reported, but evidence for transmission in other species has not been proved. this study explored pig-to-pig mers-cov transmission experimentally. virus was present in nasal swabs of infected animals, and limited amounts of viral rna, but no in ...201728653496
crystal structure of middle east respiratory syndrome coronavirus helicase.middle east respiratory syndrome coronavirus (mers-cov) remains a threat to public health worldwide; however, effective vaccine or drug against covs remains unavailable. cov helicase is one of the three evolutionary most conserved proteins in nidoviruses, thus making it an important target for drug development. we report here the first structure of full-length coronavirus helicase, mers-cov nsp13. mers-cov helicase has multiple domains, including an n-terminal cys/his rich domain (ch) with three ...201728651017
mers-cov infection: mind the public knowledge gap.in august 2015, the corona outbreak caused by middle east respiratory syndrome coronavirus (mers-cov) was the 9th episode since june 2012 in saudi arabia. little is known about the public awareness toward the nature or prevention of the disease. the aim of this work was to assess the knowledge of the adult population in riyadh toward the mers-cov. in this cross-sectional survey, a self-administrated questionnaire was distributed to randomly selected participants visiting malls in riyadh. the que ...201728647126
discovery of a highly divergent coronavirus in the asian house shrew from china illuminates the origin of the alphacoronaviruses.although shrews are one of the largest groups of mammals little is known about their role in the evolution and transmission of viral pathogens including coronaviruses. we captured 266 asian house shrews (suncus murinus) in jiangxi and zhejiang provinces, china, during 2013-2015. coronavirus (cov) rna was detected in 24 asian house shrews, with an overall prevalence of 9.02%. complete viral genome sequences were successfully recovered from the rna positive samples. the newly discovered shrew cov ...201728637760
longitudinal study of middle east respiratory syndrome coronavirus infection in dromedary camel herds in saudi arabia, 2014-2015.two herds of dromedary camels were longitudinally sampled with nasal and rectal swabs and serum, between september 2014 and may 2015, and the samples were tested for middle east respiratory syndrome (mers) coronavirus rna and antibodies. evidence of mers-cov infection was confirmed in one herd on the basis of detection of virus rna in nasal swabs from three camels and significant increases in the antibody titers from three others. the three viruses were genetically identical, thus indicating int ...201728634355
dynamics of scientific publications on the mers-cov outbreaks in saudi arabia.middle east respiratory syndrome coronavirus (mers-cov) is an emerging disease with a relatively high case fatality rate. most cases have been reported from saudi arabia, and the disease epidemic potential is considered to be limited. however, human-human transmission has occurred, usually in the context of healthcare facility-associated outbreaks. the scientific and medical community depends on timely publication of epidemiological information on emerging diseases during outbreaks to appropriat ...201728625842
dromedary camels in northern mali have high seropositivity to mers-cov.a high percentage (up to 90%) of dromedary camels in the middle east as well as eastern and central africa have antibodies to middle east respiratory syndrome coronavirus (mers-cov). here we report comparably high positivity of mers-cov antibodies in dromedary camels from northern mali. this extends the range of mers-cov further west in africa than reported to date and cautions that mers-cov should be considered in cases of severe respiratory disease in the region.201728616502
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
[construction and identification of nanobody phage display library targeting middle east respiratory syndrome coronavirus].objective to construct a phage display library of specific nano-antibodies against the middle east respiratory syndrome coronavirus (mers-cov) and apply it to the screening of neutralizing nano-antibodies. methods mers-cov receptor-binding domain (rbd) recombinant protein was used to immunize alpaca. after the last immunization, peripheral blood mononuclear cells (pbmcs) were isolated from the whole blood and total rna was extracted. the vhh gene was amplified by pcr and used to construct recomb ...201729382428
transgene expression in the genome of middle east respiratory syndrome coronavirus based on a novel reverse genetics system utilizing red-mediated recombination cloning.middle east respiratory syndrome coronavirus (mers-cov) is a high-priority pathogen in pandemic preparedness research. reverse genetics systems are a valuable tool to study viral replication and pathogenesis, design attenuated vaccines and create defined viral assay systems for applications such as antiviral screening. here we present a novel reverse genetics system for mers-cov that involves maintenance of the full-length viral genome as a cdna copy inserted in a bacterial artificial chromosome ...201728984231
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
spectrum of pathogen- and model-specific histopathologies in mouse models of acute pneumonia.pneumonia may be caused by a wide range of pathogens and is considered the most common infectious cause of death in humans. murine acute lung infection models mirror human pathologies in many aspects and contribute to our understanding of the disease and the development of novel treatment strategies. despite progress in other fields of tissue imaging, histopathology remains the most conclusive and practical read out tool for the descriptive and semiquantitative evaluation of mouse pneumonia and ...201729155867
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
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
a novel dynamic model describing the spread of the mers-cov and the expression of dipeptidyl peptidase 4.the middle east respiratory syndrome (mers) coronavirus, a newly identified pathogen, causes severe pneumonia in humans. mers is caused by a coronavirus known as mers-cov, which attacks the respiratory system. the recently defined receptor for mers-cov, dipeptidyl peptidase 4 (dpp4), is generally expressed in endothelial and epithelial cells and has been shown to be present on cultured human nonciliated bronchiolar epithelium cells. in this paper, a class of novel four-dimensional dynamic model ...201728894474
pathogen genomic surveillance elucidates the origins, transmission and evolution of emerging viral agents in china.in the past twenty years, numerous novel zoonotic viral agents with pandemic potential have emerged in china, such as the severe acute respiratory syndrome (sars) coronavirus and, more recently, the avian-origin influenza a/h7n9 virus, which have caused outbreaks among humans with high morbidity and mortality. in addition, several emerging and re-emerging viral pathogens have also been imported into china from travelers, e.g. the middle east respiratory syndrome (mers) coronavirus and zika virus ...201729270793
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
research on the mechanism of cross-species infection and transmission for animal-origin emerging and re-emerging zoonosis has won support by the national key research and development program of china.emerging and re-emerging zoonotic diseases caused by pathogens such as middle east respiratory syndrome coronavirus (mers-cov), west nile virus (wnv) or chikungunya virus (chikv) pose considerable threats to public health worldwide. research on the mechanism of cross-species infection and transmission for animal-origin emerging and re-emerging zoonosis (2016yfd0500300) has won support by the national key research and development program of china. professor wenjie tan (national institute for vira ...201730702832
exploring nursing intention, stress, and professionalism in response to infectious disease emergencies: the experience of local public hospital nurses during the 2015 mers outbreak in south korea.this study aimed to examine levels of stress and professionalism of nurses who provided nursing care during the 2015 middle east respiratory syndrome outbreak based on their experience, to investigate the nurses' intention to respond to possible future outbreaks in relation to their experience during the outbreak, and to determine the relationship between the outbreak experience and nursing intention considering stress and professionalism.201728991605
high reproduction number of middle east respiratory syndrome coronavirus in nosocomial outbreaks: mathematical modelling in saudi arabia and south korea.effective countermeasures against emerging infectious diseases require an understanding of transmission rate and basic reproduction number (r0). r0for severe acute respiratory syndrome is generally considered to be >1, whereas that for middle east respiratory syndrome (mers) is considered to be <1. however, this does not explain the large-scale outbreaks of mers that occurred in kingdom of saudi arabia (ksa) and south korean hospitals.201728958834
first confirmed case of middle east respiratory syndrome coronavirus infection in the kingdom of bahrain: in a saudi gentleman after cardiac bypass surgery.middle east respiratory syndrome coronavirus (mers-cov) is well known to cause severe respiratory infection and was first reported in the kingdom of saudi arabia in 2012. we report here the first confirmed mers-cov infection in the kingdom of bahrain in a saudi gentleman who was admitted electively for coronary bypass surgery, postoperatively developed an acute respiratory illness, and tested positive for mers-cov. 40 close contacts, all healthcare workers, were traced and followed with no docum ...201728948054
structurally guided removal of deisgylase biochemical activity from papain-like protease originating from middle east respiratory syndrome coronavirus.middle east respiratory syndrome coronavirus (mers-cov) is an emerging human pathogen that is the causative agent for middle east respiratory syndrome (mers). with mers outbreaks resulting in over 35% fatalities and now spread to 27 countries, mers-cov poses a significant ongoing threat to global human health. as part of its viral genome, mers-cov encodes a papain-like protease (plpro) that has been observed to act as a deubiquitinase and deisgylase to antagonize type i interferon (ifn-i) immune ...201728931677
public health network structure and collaboration effectiveness during the 2015 mers outbreak in south korea: an institutional collective action framework.following the 2015 middle east respiratory syndrome (mers) outbreak in south korea, this research aims to examine the structural effect of public health network explaining collaboration effectiveness, which is defined as joint efforts to improve quality of service provision, cost savings, and coordination. we tested the bonding and bridging effects on collaboration effectiveness during the mers outbreak response by utilizing an institutional collective action framework. the analysis results of 1 ...201728914780
identification of a novel inhibitor against middle east respiratory syndrome coronavirus.the middle east respiratory syndrome coronavirus (mers-cov) was first isolated in 2012, and circulated worldwide with high mortality. the continual outbreaks of mers-cov highlight the importance of developing antiviral therapeutics. here, we rationally designed a novel fusion inhibitor named mers-five-helix bundle (mers-5hb) derived from the six-helix bundle (mers-6hb) which was formed by the process of membrane fusion. mers-5hb consists of three copies of heptad repeat 1 (hr1) and two copies of ...201728906430
structural insights into the middle east respiratory syndrome coronavirus 4a protein and its dsrna binding mechanism.middle east respiratory syndrome coronavirus (mers-cov) has evolved to navigate through the sophisticated network of a host's immune system. the immune evasion mechanism including type 1 interferon and protein kinase r-mediated antiviral stress responses has been recently attributed to the involvement of mers-cov protein 4a (p4a) that masks the viral dsrna. however, the structural mechanism of how p4a recognizes and establishes contacts with dsrna is not well explained. in this study, we report ...201728900197
impact of comorbidity on fatality rate of patients with middle east respiratory syndrome.to date, 1841 cases of middle east respiratory syndrome coronavirus (mers-cov) infection have been reported worldwide, with 652 deaths. we used a publically available case line list to explore the effect of relevant factors, notably underlying comorbidities, on fatal outcome of middle east respiratory syndrome (mers) cases up to the end of october 2016. a bayesian weibull proportional hazards regression model was used to assess the effect of comorbidity, age, epidemic period and sex on the fatal ...201728900101
the predictors of 3- and 30-day mortality in 660 mers-cov patients.the mortality rate of middle east respiratory syndrome coronavirus (mers-cov) patients is a major challenge in all healthcare systems worldwide. because the mers-cov risk-standardized mortality rates are currently unavailable in the literature, the author concentrated on developing a method to estimate the risk-standardized mortality rates using mers-cov 3- and 30-day mortality measures.201728893197
mers-cov infection in a pregnant woman in korea.middle east respiratory syndrome (mers) is a lethal respiratory disease - caused by mers-coronavirus (mers-cov) which was first identified in 2012. especially, pregnant women can be expected as highly vulnerable candidates for this viral infection. in may 2015, this virus was spread in korea and a pregnant woman was confirmed with positive result of mers-cov polymerase chain reaction (pcr). her condition was improved only with conservative treatment. after a full recovery of mers, the patient ma ...201728875620
assessing the detection of middle east respiratory syndrome coronavirus igg in suspected and proven cases of middle east respiratory syndrome coronavirus infection.middle east respiratory syndrome coronavirus (mers-cov) causes severe respiratory disease with significant mortality. two testing methods are currently used for mers-cov diagnostics: nucleic acid detection (the gold standard) and serological analysis. in this study, we evaluated the detection of mers-cov-igg in suspected and proven cases of mers-cov infection. we enrolled 174 patients: 113 had respiratory symptoms/suspected mers-cov infection, 31 had confirmed influenza a or b infection, 23 had ...201728873020
a multi-faceted approach of a nursing led education in response to mers-cov infection.the emergence of the middle east respiratory syndrome-coronavirus (mers-cov) resulted in multiple healthcare associated outbreaks. in response, we developed a nurse-led program to screen and triage patients with mers-cov infection.201728869153
zoonotic origin and transmission of middle east respiratory syndrome coronavirus in the uae.since the emergence of middle east respiratory syndrome coronavirus (mers-cov) in 2012, there have been a number of clusters of human-to-human transmission. these cases of human-to-human transmission involve close contact and have occurred primarily in healthcare settings, and they are suspected to result from repeated zoonotic introductions. in this study, we sequenced whole mers-cov genomes directly from respiratory samples collected from 23 confirmed mers cases in the united arab emirates (ua ...201729239118
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