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the global spread of middle east respiratory syndrome: an analysis fusing traditional epidemiological tracing and molecular phylodynamics.since its discovery in 2012, over 1700 confirmed cases of middle east respiratory syndrome (mers) have been documented worldwide and more than a third of those cases have died. while the greatest number of cases has occurred in saudi arabia, the recent export of mers-coronavirus (mers-cov) to republic of korea showed that a pandemic is a possibility that cannot be ignored. due to the deficit of knowledge in transmission methodology, targeted treatment and possible vaccines, understanding this vi ...201629202063
transmissible gastroenteritis virus papain-like protease 1 antagonizes production of interferon-βthrough its deubiquitinase activity.coronaviruses (covs), such as human coronavirus nl63 (hcov-nl63), severe acute respiratory syndrome cov (sars-cov), murine hepatitis virus (mhv), porcine epidemic diarrhea virus (pedv), and middle east respiratory syndrome coronavirus (mers-cov), encode papain-like (pl) proteases that inhibit sendai virus- (sev-) induced interferon (ifn-β) production. recently, the crystal structure of transmissible gastroenteritis virus (tgev) pl1 has been solved, which was similar to that of sars-cov pl2pro, w ...201729201911
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
development of small-molecule viral inhibitors targeting various stages of the life cycle of emerging and re-emerging viruses.in recent years, unexpected outbreaks of infectious diseases caused by emerging and re-emerging viruses have become more frequent, which is possibly due to environmental changes. these outbreaks result in the loss of life and economic hardship. vaccines and therapeutics should be developed for the prevention and treatment of infectious diseases. in this review, we summarize and discuss the latest progress in the development of small-molecule viral inhibitors against highly pathogenic coronavirus ...201729170916
the french infectious diseases society's readiness and response to epidemic or biological risk-the current situation following the middle east respiratory syndrome coronavirus and ebola virus disease alerts.in 2012, the french infectious diseases society (french acronym spilf) initiated the "coordination of epidemic and biological risk" (spilf-coreb - emergences [sce]) group to support the readiness and response of healthcare workers (hcws) to new alerts.201729169817
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
corticosteroid therapy for critically ill patients with the middle east respiratory syndrome.corticosteroid therapy is commonly used among critically ill patients with the middle east respiratory syndrome (mers), but its impact on outcomes is uncertain. analyses of observational studies often do not account for patients' clinical condition at the time of corticosteroid therapy initiation.201729161116
human monoclonal antibodies as candidate therapeutics against emerging viruses.the emergence of new pathogens, such as severe acute respiratory syndrome coronavirus (sars-cov), middle east respiratory syndrome coronavirus (mers-cov), and ebola virus, poses serious challenges to global public health and highlights the urgent need for novel antiviral approaches. monoclonal antibodies (mabs) have been successfully used to treat various diseases, particularly cancer and immunological disorders. antigen-specific mabs have been isolated using several different approaches, includ ...201729159596
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
us federal travel restrictions for persons with higher-risk exposures to communicable diseases of public health concern.published guidance recommends controlled movement for persons with higher-risk exposures (hres) to communicable diseases of public health concern; us federal public health travel restrictions (phtrs) might be implemented to enforce these measures. we describe persons eligible for and placed on phtrs because of hres during 2014-2016. there were 160 persons placed on phtrs: 142 (89%) involved exposure to ebola virus, 16 (10%) to lassa fever virus, and 2 (1%) to middle east respiratory syndrome cor ...201729155659
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
human intestinal tract serves as an alternative infection route for middle east respiratory syndrome coronavirus.middle east respiratory syndrome coronavirus (mers-cov) has caused human respiratory infections with a high case fatality rate since 2012. however, the mode of virus transmission is not well understood. the findings of epidemiological and virological studies prompted us to hypothesize that the human gastrointestinal tract could serve as an alternative route to acquire mers-cov infection. we demonstrated that human primary intestinal epithelial cells, small intestine explants, and intestinal orga ...201729152574
one health and zoonoses: the evolution of one health and incorporation of zoonoses.zoonotic disease outbreaks have surged in the last two decades. these include severe acute respiratory syndrome (sars), hendra virus, nipah virus, influenza viruses, middle east respiratory syndrome (mers) coronavirus, and ebola. one health is the initiative of an inclusive collaboration linking human, animal, and environmental health. one health is advocated through an intersectoral coordination to combat zoonoses, and the term has evolved over centuries. the primary aim of this literature revi ...201529138713
healthcare worker infected with middle east respiratory syndrome during cardiopulmonary resuscitation in korea, 2015.during the outbreak of the middle east respiratory syndrome (mers) in korea in 2015, the korea centers for disease control and prevention (kcdc) confirmed a case of mers in a healthcare worker in daejeon, south korea. to verify the precise route of infection for the case, we conducted an in-depth epidemiological investigation in cooperation with the kcdc.201729129042
nsp3 of coronaviruses: structures and functions of a large multi-domain protein.the multi-domain non-structural protein 3 (nsp3) is the largest protein encoded by the coronavirus (cov) genome, with an average molecular mass of about 200 kd. nsp3 is an essential component of the replication/transcription complex. it comprises various domains, the organization of which differs between cov genera, due to duplication or absence of some domains. however, eight domains of nsp3 exist in all known covs: the ubiquitin-like domain 1 (ubl1), the glu-rich acidic domain (also called "hy ...201829128390
no mers-cov but positive influenza viruses in returning hajj pilgrims, china, 2013-2015.there is global health concern that the mass movement of pilgrims to and from mecca annually could contribute to the international spread of middle east respiratory syndrome coronavirus (mers-cov). in china, about 11,000 muslim pilgrims participate in the hajj gathering in mecca annually. this is the first report of mers-cov and respiratory virus molecular screening of returning pilgrims at points of entry in china from 2013 to 2015.201729126397
design and delivery of therapeutic sirnas: application to mers-coronavirus.the mers-cov is a novel human coronavirus causing respiratory syndrome since april 2012. the replication of mers-cov is mediated by orf 1ab and viral gene activity can be modulated by rnai approach. the inhibition of virus replication has been documented in cell culture against multiple viruses by rnai approach. currently, very few sirna against mers-cov have been computationally designed and published.201729119921
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
follow-up chest radiographic findings in patients with mers-cov after recovery.to evaluate the follow-up chest radiographic findings in patients with middle east respiratory syndrome coronavirus (mers-cov) who were discharged from the hospital following improved clinical symptoms.201729089687
a pandemic risk assessment of middle east respiratory syndrome coronavirus (mers-cov) in saudi arabia.since the initial emergence of middle east respiratory syndrome coronavirus (mers-cov) in 2012, a high incidence rate has been observed in saudi arabia. this suggests that the country is at continuous risk. the epidemic level of mers-cov infection was examined in saudi arabia by the susceptible-infectious-recovered (sir) model using a bayesian approach for estimation of time dependent reproduction number (r) across a two-year interval (may, 2013-may, 2015) in five defined clusters, followed by s ...201729062261
retrospective, epidemiological cluster analysis of the middle east respiratory syndrome coronavirus (mers-cov) epidemic using open source data.the middle east respiratory syndrome coronavirus (mers-cov) is caused by a novel coronavirus discovered in 2012. since then, 1806 cases, including 564 deaths, have been reported by the kingdom of saudi arabia (ksa) and affected countries as of 1 june 2016. previous literature attributed increases in mers-cov transmission to camel breeding season as camels are likely the reservoir for the virus. however, this literature review and subsequent analysis indicate a lack of seasonality. a retrospectiv ...201729061208
re: "assessing the detection of middle east respiratory syndrome coronavirus igg in suspected and proven cases of middle east respiratory syndrome coronavirus infection" by alhetheel et al. (viral immunol 2017;30:649-653.). 201729058554
development of middle east respiratory syndrome coronavirus vaccines - advances and challenges.middle east respiratory syndrome coronavirus (mers-cov) is an emerging pathogen with the potential to pose a threat to global public health. sporadic cases and outbreaks continue to be reported in the middle east, and case fatality rates remain high at approximately 36% globally. no specific preventive or therapeutic countermeasures currently exist. a safe and effective vaccine could play an important role in protecting against the threat from mers-cov. this review discusses human vaccine candid ...201829048984
nosocomial amplification of mers-coronavirus in south korea, 2015.nosocomial amplification resulted in nearly 200 cases of middle east respiratory syndrome (mers) during the 2015 south korean mers-coronavirus outbreak. it remains unclear whether certain types of cases were more likely to cause secondary infections than others, and if so, why.201729044371
molecular evolution of mers coronavirus: dromedaries as a recent intermediate host or long-time animal reservoir?while dromedary camels are the immediate animal source of mers coronavirus (mers-cov) infection, the evolutionary origin of mers-cov remains obscure. we analyzed 219 camel and human mers-cov genome sequences available in genbank. phylogenetic analysis showed that 5 and 214 strains belong to clade a and b, respectively, with clade a further divided into lineage a1 (3 human strains) and lineage a2 (2 camel strains), and clade b divided into b1 to b6 (each containing both human and camel strains). ...201729035289
influenza is more common than middle east respiratory syndrome coronavirus (mers-cov) among hospitalized adult saudi patients.since the initial description of middle east respiratory syndrome coronavirus (mers-cov), we adopted a systematic process of screening patients admitted with community acquired pneumonia. here, we report the result of the surveillance activity in a general hospital in saudi arabia over a four year period.201729031867
influenza virus but not mers coronavirus circulation in iran, 2013-2016: comparison between pilgrims and general population.the pilgrimage to mecca and karbala bring many muslims to a confined area. respiratory tract infections are the most common diseases transmitted during mass gatherings in hajj, umrah and karbala. the aim of this study was to determine and compare the prevalence of middle east respiratory syndrome coronavirus (mers-cov) and influenza virus infections among iranian general population and pilgrims with severe acute respiratory infections (sari) returning from mecca and karbala during 2013-2016.201729031546
investigation of nonlinear epidemiological models for analyzing and controlling the mers outbreak in korea.much concern has arisen regarding serious epidemics due to the middle east respiratory syndrome (mers) coronavirus. the first mers case of korea was reported on 20 may 2015, and since then, the mers outbreak in korea has resulted in hundreds of confirmed cases and tens of deaths. deadly infectious diseases such as mers have significant direct and indirect social impacts, which include disease-induced mortality and economic losses. also, a delayed response to the outbreak and underestimating its ...201829031518
occurrence of the middle east respiratory syndrome coronavirus (mers-cov) across the gulf corporation council countries: four years update.the emergence of the middle east respiratory syndrome coronavirus (mers-cov) infections has become a global issue of dire concerns. mers-cov infections have been identified in many countries all over the world whereas high level occurrences have been documented in the middle east and korea. mers-cov is mainly spreading across the geographical region of the middle east, especially in the arabian peninsula, while some imported sporadic cases were reported from the europe, north america, africa, an ...201729028812
dpp4, the middle east respiratory syndrome coronavirus receptor, is upregulated in lungs of smokers and chronic obstructive pulmonary disease patients.middle east respiratory syndrome coronavirus (mers-cov) causes pneumonia with a relatively high case fatality rate in humans. smokers and chronic obstructive pulmonary disease (copd) patients have been reported to be more susceptible to mers-cov infection. here, we determined the expression of mers-cov receptor, dipeptidyl peptidase iv (dpp4), in lung tissues of smokers without airflow limitation and copd patients in comparison to nonsmoking individuals (never-smokers).201829020176
cross-sectional study of mers-cov-specific rna and antibodies in animals that have had contact with mers patients in saudi arabia.middle east respiratory syndrome coronavirus (mers-cov) is a newly emerged coronavirus that is associated with a severe respiratory disease in humans in the middle east. the epidemiological profiles of the mers-cov infections suggest zoonotic transmission from an animal reservoir to humans.201728993171
characterization of novel monoclonal antibodies against the mers-coronavirus spike protein and their application in species-independent antibody detection by competitive elisa.since discovering the middle east respiratory syndrome coronavirus (mers-cov) as a causative agent of severe respiratory illness in the middle east in 2012, serological testing has been conducted to assess antibody responses in patients and to investigate the zoonotic reservoir of the virus. although the virus neutralization test is the gold standard assay for mers diagnosis and for investigating the zoonotic reservoir, it uses live virus and so must be performed in high containment laboratories ...201828993122
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
nmr structure and localization of a large fragment of the sars-cov fusion protein: implications in viral cell fusion.the lethal coronaviruses (covs), severe acute respiratory syndrome-associated coronavirus (sars-cov) and most recently middle east respiratory syndrome coronavirus, (mers-cov) are serious human health hazard. a successful viral infection requires fusion between virus and host cells carried out by the surface spike glycoprotein or s protein of cov. current models propose that the s2 subunit of s protein assembled into a hexameric helical bundle exposing hydrophobic fusogenic peptides or fusion pe ...201828988778
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
a study of the probable transmission routes of mers-cov during the first hospital outbreak in the republic of korea.infections caused by the middle east respiratory syndrome coronavirus (mers-cov) are a serious health issue due to their prevalence and associated mortality. however, the transmission routes of the virus remain unclear, and thus, the current recommended control strategies are not evidence based. in this study, we investigated the transmission routes of mers-cov during the first nosocomial outbreak in the republic of korea in may 2015 using a multi-agent modeling framework. we identified seven hy ...201828960494
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
middle east respiratory syndrome coronavirus transmission among health care workers: implication for infection control.many outbreaks of middle east respiratory syndrome coronavirus (mers-cov) have occurred in health care settings and involved health care workers (hcws). we describe the occurrence of an outbreak among hcws and attempt to characterize at-risk exposures to improve future infection control interventions.201828958446
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
human coronaviruses: a review of virus-host interactions.human coronaviruses (hcovs) are known respiratory pathogens associated with a range of respiratory outcomes. in the past 14 years, the onset of severe acute respiratory syndrome coronavirus (sars-cov) and middle east respiratory syndrome coronavirus (mers-cov) have thrust hcovs into spotlight of the research community due to their high pathogenicity in humans. the study of hcov-host interactions has contributed extensively to our understanding of hcov pathogenesis. in this review, we discuss som ...201628933406
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
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
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
inclusion of mers-spike protein elisa in algorithm to determine serologic evidence of mers-cov infection.the centers for disease control and prevention (cdc) algorithm for detecting presence of serum antibodies against middle east respiratory syndrome coronavirus (mers-cov) in subjects with potential infections with the virus has included screening by indirect elisa against recombinant nucleocapsid (n) protein and confirmation by immunofluorescent staining of infected monolayers and/or microneutralization titration. other international groups include indirect elisa assays using the spike (s) protei ...201828906003
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
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
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
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
clinical pearls in venovenous extracorporeal life support for adult respiratory failure.extracorporeal life support (ecls) has been widely utilized to treat neonatal respiratory failure for two decades. however, its uptake in the case of adult respiratory failure has been slow because of a paucity of quality evidence and a sluggish tempo of ecls-related technological advances. in recent years, interest in ecls has been piqued after encouraging results were reported from its use during the 2009 h1n1 influenza pandemic. in a world constantly under threat from another influenza epidem ...201828885377
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
current treatment options and the role of peptides as potential therapeutic components for middle east respiratory syndrome (mers): a review.middle east respiratory syndrome coronavirus (mers-cov) is a highly pathogenic respiratory virus with mechanisms that may be driven by innate immune responses. despite the effort of scientific studies related to this virus, middle east respiratory syndrome (mers) is still a public health concern. mers-cov infection has a high mortality rate, and to date, no therapeutic or vaccine has been discovered, that is effective in treating or preventing the disease. in this review, we summarize our unders ...201828864360
histopathology of middle east respiratory syndrome coronovirus (mers-cov) infection - clinicopathological and ultrastructural study.the pathogenesis, viral localization and histopathological features of middle east respiratory syndrome - coronavirus (mers-cov) in human are not sufficiently described. the aims of this study were to explore and define the spectrum of histological and ultrastructural pathological changes affecting various organs in a patient with mers-cov infection and represent a base of mers-cov histopathology.201728858401
a review of candidate therapies for middle east respiratory syndrome from a molecular perspective.there have been 2040 laboratory-confirmed cases of middle east respiratory syndrome coronavirus (mers-cov) in 27 countries, with a mortality rate of 34.9 %. there is no specific therapy. the current therapies have mainly been adapted from severe acute respiratory syndrome (sars-cov) treatments, including broad-spectrum antibiotics, corticosteroids, interferons, ribavirin, lopinavir-ritonavir or mycophenolate mofetil, and have not been subject to well-organized clinical trials. the development of ...201728855003
establishment and application of a universal coronavirus screening method using maldi-tof mass spectrometry.there are four human coronaviruses (hcovs), distributed worldwide, that are associated with a range of respiratory symptoms. the discovery of severe acute respiratory syndrome (sars)-cov and middle east respiratory syndrome (mers)-cov shows that hcovs pose a significant threat to human health. our work aims to develop a sensitive method (mcov-ms) which can not only identify known hcovs accurately, but also have the ability to provide clues for the emerging hcovs. the method was performed using a ...201728848521
vaccines for emerging infectious diseases: lessons from mers coronavirus and zika virus.the past decade and a half has been characterized by numerous emerging infectious diseases. with each new threat, there has been a call for rapid vaccine development. pathogens such as the middle east respiratory syndrome coronavirus (mers-cov) and the zika virus represent either new viral entities or viruses emergent in new geographic locales and characterized bywith novel complications. both serve as paradigms for the global spread that can accompany new pathogens. in this paper, we review the ...201728846484
malonic acid diazo esters for c,h - insertion crosslinking (chic) reactions: a versatile and powerful tool forthe generation of tailor made surfaces.we report on a simple and versatile way for the modification of a broad spectrum of surfaces with thin polymer films through the thermally or photo-chemically induced generation of surface-attached polymer networks. the system is based on copoly-mers containingdiazomalonate groups which can be activated by heat or light. to this end, the co-polymers are deposited from solution onto organic or inorganic substrates. upon activation the diaz-omalonate decomposes and forms a carbene, which inducesc- ...201728846177
a47 origin and possible genetic recombination of the middle east respiratory syndrome coronavirus from the first imported case in china: phylogenetics and coalescence analysis. 201728845291
a25 phylogenetic analysis of the nucleocapsid and rna-dependent rna polymerase fragments of the first imported case of middle east respiratory syndrome coronavirus (mers-cov) infection in the philippines from saudi arabia, february 2015. 201728845258
a46 mers-cov in arabian camels in africa and central asia. 201728845242
mers coronavirus nsp1 participates in an efficient propagation through a specific interaction with viral rna.mers-cov is the only lethal human cov still endemic in the arabian peninsula and neither vaccine nor therapeutics against mers-cov infection is available. the nsp1 of cov is thought to be a major virulence factor because it suppresses protein synthesis through the degradation of host mrna. in contrast, viral rna circumvents the nsp1-mediated translational shutoff for an efficient propagation. in this study, we identified amino acid residue in mers-cov nsp1 that differ from those of sars-cov nsp1 ...201728843094
ensvmb: metagenomics fragments classification using ensemble svm and blast.metagenomics brings in new discoveries and insights into the uncultured microbial world. one fundamental task in metagenomics analysis is to determine the taxonomy of raw sequence fragments. modern sequencing technologies produce relatively short fragments and greatly increase the number of fragments, and thus make the taxonomic classification considerably more difficult than before. therefore, fast and accurate techniques are called to classify large-scale fragments. we propose ensvm (ensemble ...201728842700
performance evaluation of the powerchek mers (upe & orf1a) real-time pcr kit for the detection of middle east respiratory syndrome coronavirus rna.molecular detection of middle east respiratory syndrome coronavirus (mers-cov) using real-time reverse transcription (rrt)-pcr assays is the method of choice for diagnosis of mers. we evaluated the performance of the powerchek mers (upe & orf1a) real-time pcr kit (powerchek mers assay; kogene biotech, korea) a one-step rrt-pcr assay for the qualitative detection of mers-cov.201728840986
imported case of middle east respiratory syndrome coronavirus (mers-cov) infection from oman to thailand, june 2015.thailand reported the first middle east respiratory syndrome (mers) case on 18 june 2015 (day 4) in an omani patient with heart condition who was diagnosed with pneumonia on hospital admission on 15 june 2015 (day 1). two false negative rt-pcr on upper respiratory tract samples on days 2 and 3 led to a 48-hour diagnosis delay and a decision to transfer the patient out of the negative pressure unit (npu). subsequent examination of sputum later on day 3 confirmed mers coronavirus (mers-cov) infect ...201728840828
use of high b value diffusion-weighted magnetic resonance imaging in acute encephalopathy/encephalitis during childhood.to determine the use of high b value diffusion-weighted imaging (dwi) in the diagnosis and assessment of acute febrile encephalopathy/encephalitis in childhood.201728838686
encephalitis with reversible splenial and deep cerebral white matter lesions associated with epstein-barr virus infection in adults.approximately 200 cases of mild encephalitis with reversible splenial (mers) and deep cerebral white matter lesions have been reported since mers was first defined in 2004. mers occurs more frequently in children; in adults, only ~60 cases have been reported. until now, only four cases of mers in adults have been associated with epstein-barr virus (ebv).201728831257
mers-cov accessory orfs play key role for infection and pathogenesis.while dispensable for viral replication, coronavirus (cov) accessory open reading frame (orf) proteins often play critical roles during infection and pathogenesis. utilizing a previously generated mutant, we demonstrate that the absence of all four middle east respiratory syndrome cov (mers-cov) accessory orfs (deletion of orf3, -4a, -4b, and -5 [dorf3-5]) has major implications for viral replication and pathogenesis. importantly, attenuation of the dorf3-5 mutant is primarily driven by dysregul ...201728830941
elucidating transmission patterns from internet reports: ebola and middle east respiratory syndrome as case studies.the paucity of traditional epidemiological data during epidemic emergencies calls for alternative data streams to characterize the key features of an outbreak, including the nature of risky exposures, the reproduction number, and transmission heterogeneities. we illustrate the potential of internet data streams to improve preparedness and response in outbreak situations by drawing from recent work on the 2014-2015 ebola epidemic in west africa and the 2015 middle east respiratory syndrome (mers) ...201628830110
middle east respiratory syndrome coronavirus: five years later.in the past five years, there have been 1,936 laboratory-confirmed cases of middle east respiratory syndrome coronavirus (mers-cov) in 27 countries, with a mortality rate of 35.6%. most cases have arisen in the middle east, particularly the kingdom of saudi arabia, however there was a large hospital-associated outbreak in the republic of korea in 2015. exposure to dromedary camels has been recognized by the world health organization (who) as a risk factor in primary cases, but the exact mechanis ...201728826284
serologic responses of 42 mers-coronavirus-infected patients according to the disease severity.we evaluated serologic response of 42 middle east respiratory syndrome coronavirus (mers-cov)-infected patients according to 4 severity groups: asymptomatic infection (group 0), symptomatic infection without pneumonia (group 1), pneumonia without respiratory failure (group 2), and pneumonia progressing to respiratory failure (group 3). none of the group 0 patients showed seroconversion, while the seroconversion rate gradually increased with increasing disease severity (0.0%, 60.0%, 93.8%, and 10 ...201728821364
conveyance contact investigation for imported middle east respiratory syndrome cases, united states, may 2014.in 2014, the centers for disease control and prevention conducted conveyance contact investigations for 2 middle east respiratory syndrome cases imported into the united states, comprising all passengers and crew on 4 international and domestic flights and 1 bus. of 655 contacts, 78% were interviewed; 33% had serologic testing. no secondary cases were identified.201728820379
a random forest classifier for detecting rare variants in ngs data from viral populations.we propose a random forest classifier for detecting rare variants from sequencing errors in next generation sequencing (ngs) data from viral populations. the method utilizes counts of varying length of k-mers from the reads of a viral population to train a random forest classifier, called multires, that classifies k-mers as erroneous or rare variants. our algorithm is rooted in concepts from signal processing and uses a frame-based representation of k-mers. frames are sets of non-orthogonal basi ...201728819548
enhanced inflammation in new zealand white rabbits when mers-cov reinfection occurs in the absence of neutralizing antibody.the middle east respiratory syndrome coronavirus (mers-cov) is a zoonotic betacoronavirus that was first detected in humans in 2012 as a cause of severe acute respiratory disease. as of july 28, 2017, there have been 2,040 confirmed cases with 712 reported deaths. while many infections have been fatal, there have also been a large number of mild or asymptomatic cases discovered through monitoring and contact tracing. new zealand white rabbits are a possible model for asymptomatic infection with ...201728817732
serogrouping and seroepidemiology of north european hantaviruses using a novel broadly targeted synthetic nucleoprotein antigen array.introduction: hantaviruses are globally distributed zoonotic pathogens. great diversity and high antigenic cross-reactivity makes diagnosis by traditional methods cumbersome. materials and methods: 'megapeptides', 119-120-mers from the amino terminus of the nucleoprotein of 16 hantaviruses, representing the four major branches of the hantavirus phylogenetic tree, were utilized in a novel igg-based hantavirus suspension multiplex immunoassay (hsmia) for detection of past hantavirus infections in ...201728815001
large-scale machine learning of media outlets for understanding public reactions to nation-wide viral infection outbreaks.from may to july 2015, there was a nation-wide outbreak of middle east respiratory syndrome (mers) in korea. mers is caused by mers-cov, an enveloped, positive-sense, single-stranded rna virus belonging to the family coronaviridae. despite expert opinions that the danger of mers might be exaggerated, there was an overreaction by the public according to the korean mass media, which led to a noticeable reduction in social and economic activities during the outbreak. to explain this phenomenon, we ...201728813689
prevalence of antibodies against the middle east respiratory syndrome coronavirus, influenza a and b viruses among blood donors, saudi arabia. 201728808497
immunogenicity and structures of a rationally designed prefusion mers-cov spike antigen.middle east respiratory syndrome coronavirus (mers-cov) is a lineage c betacoronavirus that since its emergence in 2012 has caused outbreaks in human populations with case-fatality rates of ∼36%. as in other coronaviruses, the spike (s) glycoprotein of mers-cov mediates receptor recognition and membrane fusion and is the primary target of the humoral immune response during infection. here we use structure-based design to develop a generalizable strategy for retaining coronavirus s proteins in th ...201728807998
evaluation and clinical validation of two field-deployable reverse transcription-insulated isothermal pcr assays for the detection of the middle east respiratory syndrome coronavirus.middle east respiratory syndrome (mers) is an emerging zoonotic viral respiratory disease that was first identified in saudi arabia in 2012. in 2015, the largest mers outbreak outside of the middle east region occurred in the republic of korea. the rapid nosocomial transmission of mers-coronavirus (mers-cov) in korean healthcare settings highlighted the importance and urgent need for a rapid and reliable on-site diagnostic assay to implement effective control and preventive measures. here, we de ...201728807812
what we are watching-top global infectious disease threats, 2013-2016: an update from cdc's global disease detection operations center.to better track public health events in areas where the public health system is unable or unwilling to report the event to appropriate public health authorities, agencies can conduct event-based surveillance, which is defined as the organized collection, monitoring, assessment, and interpretation of unstructured information regarding public health events that may represent an acute risk to public health. the us centers for disease control and prevention's (cdc's) global disease detection operati ...201728805465
advancing preparedness for highly hazardous contagious diseases: admitting 10 simulated patients with mers-cov.the ebola outbreak of 2014-2016 highlighted the need for the development of a more robust healthcare infrastructure in the united states to provide isolation care for patients infected with a highly hazardous contagious disease. routine exercises and skills practice are required to effectively and safely prepare care teams to confidently treat this special population of patients. the nebraska biocontainment unit (nbu) at nebraska medicine in omaha has been conducting exercises since 2005 when th ...201728805464
new episode of middle east respiratory syndrome coronavirus outbreak in saudi arabia: an emerging public health threat. 201728802180
sequence homology between hla-bound cytomegalovirus and human peptides: a potential trigger for alloreactivity.human cytomegalovirus (hcmv) reactivation may often coincide with the development of graft-versus-host-disease (gvhd) in stem cell transplantation (sct). seventy seven sct donor-recipient pairs (drp) (hla matched unrelated donor (mud), n = 50; matched related donor (mrd), n = 27) underwent whole exome sequencing to identify single nucleotide polymorphisms (snps) generating alloreactive peptide libraries for each drp (9-mer peptide-hla complexes); human cmv cross (cross-reactive open source seque ...201728800601
a molecular breadboard: removal and replacement of subunits in an hepatitis b virus capsid.hepatitis b virus (hbv) core protein is a model system for studying assembly and disassembly of icosahedral structures. controlling disassembly will allow re-engineering the 120 subunit hbv capsid, making it a molecular breadboard. we examined removal of subunits from partially crosslinked capsids to form stable incomplete particles. to characterize incomplete capsids, we used two single molecule techniques, resistive-pulse sensing and charge detection mass spectrometry. we expected to find a bi ...201728795465
an efficient strategy using k-mers to analyse 16s rrna sequences.the use of k-mers has been a successful strategy for improving metagenomics studies, including taxonomic classifications, or de novo assemblies, and can be used to obtain sequences of interest from the available databases. the aim of this manuscript was to propose a simple but efficient strategy to generate k-mers and to use them to obtain and analyse in silico 16s rrna sequence fragments. a total of 513,309 bacterial sequences contained in the silva database were considered for the study, and h ...201728795166
the history and epidemiology of middle east respiratory syndrome corona virus.corona viruses cause common cold, and infections caused by corona viruses are generally self-resolving. during the last 4 years, corona viruses have become the most important viruses worldwide because of the occurrence of several recent deaths caused by corona viruses in saudi arabia. spread of the infection occurred worldwide; however, most cases of mortality have occurred in the middle east. owing to the predominance of outbreaks in the middle eastern countries, the virus was renamed a middle ...201728794876
recovery from the middle east respiratory syndrome is associated with antibody and t-cell responses.the middle east respiratory syndrome coronavirus (mers-cov) causes a highly lethal pneumonia. mers was recently identified as a candidate for vaccine development, but most efforts focus on antibody responses, which are often transient after cov infections. cov-specific t cells are generally long-lived, but the virus-specific t cell response has not been addressed in mers patients. we obtained peripheral blood mononuclear cells and/or sera from 21 mers survivors. we detected mers-cov-specific cd4 ...201728778905
suggestions on improvement of infectious disease law and regulations.the study's perspective is through examining an enactment for the new amendment for legislation, to make proposals for a more rational and concrete basis in the interpretation and application of the korean legal regime in global infectious disease emergency situations.201728774161
evolution and emergence of pathogenic viruses: past, present, and future.incidences of emerging/re-emerging deadly viral infections have significantly affected human health despite extraordinary progress in the area of biomedical knowledge. the best examples are the recurring outbreaks of dengue and chikungunya fever in tropical and sub-tropical regions, the recent epidemic of zika in the americas and the caribbean, and the sars, mers, and influenza a outbreaks across the globe. the established natural reservoirs of human viruses are mainly farm animals, and, to a le ...201728772262
comparative genomic analysis mers cov isolated from humans and camels with special reference to virus encoded helicase.middle east respiratory syndrome coronavirus (mers cov) is a new emerging viral disease characterized by high fatality rate. understanding mers cov genetic aspects and codon usage pattern is important to understand mers cov survival, adaptation, evolution, resistance to innate immunity, and help in finding the unique aspects of the virus for future drug discovery experiments. in this work, we provide comprehensive analysis of 238 mers cov full genomes comprised of human (hmers) and camel (cmers) ...201728769010
the tetraspanin cd9 facilitates mers-coronavirus entry by scaffolding host cell receptors and proteases.infection by enveloped coronaviruses (covs) initiates with viral spike (s) proteins binding to cellular receptors, and is followed by proteolytic cleavage of receptor-bound s proteins, which prompts s protein-mediated virus-cell membrane fusion. infection therefore requires close proximity of receptors and proteases. we considered whether tetraspanins, scaffolding proteins known to facilitate cov infections, hold receptors and proteases together on cell membranes. using knockout cell lines, we f ...201728759649
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
a comprehensive review of common bacterial, parasitic and viral zoonoses at the human-animal interface in egypt.egypt has a unique geographical location connecting the three old-world continents africa, asia and europe. it is the country with the highest population density in the middle east, northern africa and the mediterranean basin. this review summarizes the prevalence, reservoirs, sources of human infection and control regimes of common bacterial, parasitic and viral zoonoses in animals and humans in egypt. there is a gap of knowledge conerning the epidemiology of zoonotic diseases at the human-anim ...201728754024
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
effective therapy with infliximab for clinically mild encephalitis/encephalopathy with a reversible splenial lesion in an infant with kawasaki disease.kawasaki disease (kd) is a systemic vasculitis in infants. in kd, encephalopathy is rarely (0.1%) associated, however, clinically mild encephalitis/encephalopathy with a reversible splenial lesion (mers) has previously been reported in some pediatric patients. here, we report on a 2-year-old girl who had kd complicated with mers. the patient experienced generalized clonic convulsion and prolonged consciousness disturbance with fever for 2 days. her head mri showed a high signal intensity lesion ...201728747606
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
short (16-mer) locked nucleic acid splice-switching oligonucleotides restore dystrophin production in duchenne muscular dystrophy myotubes.splice-switching antisense oligonucleotides (ssos) offer great potential for rna-targeting therapies, and two sso drugs have been recently approved for treating duchenne muscular dystrophy (dmd) and spinal muscular atrophy (sma). despite promising results, new developments are still needed for more efficient chemistries and delivery systems. locked nucleic acid (lna) is a chemically modified nucleic acid that presents several attractive properties, such as high melting temperature when bound to ...201728742140
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