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characteristics and outcome of viral pneumonia caused by influenza and middle east respiratory syndrome-coronavirus infections: a 4-year experience from a tertiary care center.after the emergence of new influenza viruses, the morbidity and mortality of viral pneumonia have received a great attention.202031333767
superior immune responses induced by intranasal immunization with recombinant adenovirus-based vaccine expressing full-length spike protein of middle east respiratory syndrome coronavirus.middle east respiratory syndrome coronavirus (mers-cov) causes an acute and severe lower respiratory illness as well as vomiting, diarrhea, and renal failure. because no licensed mers-cov vaccines are currently available, preventive and therapeutic measures are urgently needed. the surface spike (s) glycoprotein of mers-cov, which binds to the cellular receptor dipeptidyl peptidase 4 (dpp4), is considered as a major target for mers-cov vaccine development. here, we designed recombinant replicati ...201931329652
spatiotemporal clustering of middle east respiratory syndrome coronavirus (mers-cov) incidence in saudi arabia, 2012-2019.middle east respiratory syndrome coronavirus (mers-cov) is a great public health concern globally. although 83% of the globally confirmed cases have emerged in saudi arabia, the spatiotemporal clustering of mers-cov incidence has not been investigated. this study analysed the spatiotemporal patterns and clusters of laboratory-confirmed mers-cov cases reported in saudi arabia between june 2012 and march 2019. temporal, seasonal, spatial and spatiotemporal cluster analyses were performed using kul ...201931311073
structural definition of a neutralization epitope on the n-terminal domain of mers-cov spike glycoprotein.most neutralizing antibodies against middle east respiratory syndrome coronavirus (mers-cov) target the receptor-binding domain (rbd) of the spike glycoprotein and block its binding to the cellular receptor dipeptidyl peptidase 4 (dpp4). the epitopes and mechanisms of mabs targeting non-rbd regions have not been well characterized yet. here we report the monoclonal antibody 7d10 that binds to the n-terminal domain (ntd) of the spike glycoprotein and inhibits the cell entry of mers-cov with high ...201931296843
knowledge and practices of dentists regarding mers-cov. a cross-sectional survey in saudi arabia.to assess virus knowledge among dentists in saudi arabia and to identify factors associated with recommended management practices of patients. method: a structured questionnaire was distributed to dentists in major saudi cities between september 2016 and december 2017. the questionnaire investigated participants' knowledge about middle east respiratory syndrome coronavirus (mers-cov) transmission, consequences, patient identification and history taking practices. data was collected using paper-b ...201931287133
verification and diagnostic evaluation of the realstar® middle east respiratory syndrome coronavirus (n gene) reverse transcription-pcr kit 1.0.aim: we report the diagnostic evaluation of a confirmatory reverse transcription-pcr (rt-pcr) kit targeting the middle east respiratory syndrome coronavirus (mers-cov) n gene. material & methods: 33 patient samples from two collections sites in riyadh, saudi arabia, which were pre-characterized via real-time rt-pcr targeting mers-cov orf1a and upe, and were tested using the mers-cov n gene, as a confirmatory assay. this diagnostic procedure follows a two-step diagnostics scheme, recommended by t ...201931271059
controversy around airborne versus droplet transmission of respiratory viruses: implication for infection prevention.health agencies recommend transmission-based precautions, including contact, droplet and airborne precautions, to mitigate transmission of respiratory viruses in healthcare settings. there is particular controversy over the importance of aerosol transmission and whether airborne precautions should be recommended for some respiratory viruses. here, we review the current recommendations of transmission-based precautions and the latest evidence on the aerosol transmission of respiratory viruses.201931259864
narrative review of middle east respiratory syndrome coronavirus (mers-cov) infection: updates and implications for practice. 202031256729
effectiveness of an education health programme about middle east respiratory syndrome coronavirus tested during travel consultations.we aimed to evaluate the level of knowledge of middle east respiratory syndrome coronavirus (mers-cov) among hajj pilgrims before and after an education health programme during international vaccine consultations in france.201931252151
detection of multiple viral sequences in the respiratory tract samples of suspected middle east respiratory syndrome coronavirus patients in jakarta, indonesia 2015-2016.the identification and analysis of viral etiological agents from suspected middle east respiratory syndrome coronavirus (mers-cov) cases admitted to prof. dr. sulianti saroso infectious disease hospital (idh) using molecular assays.201931238156
human coronavirus: host-pathogen interaction.human coronavirus (hcov) infection causes respiratory diseases with mild to severe outcomes. in the last 15 years, we have witnessed the emergence of two zoonotic, highly pathogenic hcovs: severe acute respiratory syndrome coronavirus (sars-cov) and middle east respiratory syndrome coronavirus (mers-cov). replication of hcov is regulated by a diversity of host factors and induces drastic alterations in cellular structure and physiology. activation of critical signaling pathways during hcov infec ...201931226023
preventive behavioral responses to the 2015 middle east respiratory syndrome coronavirus outbreak in korea.this study examined the public's preventive behavioral responses during the 2015 middle east respiratory syndrome coronavirus (mers-cov) outbreak in korea and the influencing factors. two cross-sectional telephone surveys were conducted by gallup korea using random digit dialing in june 2015 (n = 2004). the main outcome variables were nonpharmaceutical preventive measures (survey (1): measures for reducing transmission (handwashing, face masks); and survey (2): measures for avoiding contact with ...201931216779
correction: case characteristics among middle east respiratory syndrome coronavirus outbreak and non-outbreak cases in saudi arabia from 2012 to 2015. 201931175202
antibodies and vaccines against middle east respiratory syndrome coronavirus.the middle east respiratory syndrome coronavirus (mers-cov) has spread through 27 countries and infected more than 2,200 people since its first outbreak in saudi arabia in 2012. the high fatality rate (35.4%) of this novel coronavirus and its persistent wide spread infectiousness in animal reservoirs have generated tremendous global public health concern. however, no licensed therapeutic agents or vaccines against mers-cov are currently available and only a limited few have entered clinical tria ...201931169078
generation of full-length infectious cdna clones of middle east respiratory syndrome coronavirus.middle east respiratory syndrome coronavirus (mers-cov) was first identified in saudi arabia in 2012 and related infection cases have been reported in over 20 countries. roughly 10,000 human cases have so far been reported in total with fatality rates at up to 40%. the majority of cases have occurred in saudi arabia with mostly sporadic outbreaks outside the country except for the one in south korea in 2015. the korean mers-cov strain was isolated from the second korean patient and its genome wa ...201931154749
a yeast suppressor screen used to identify mammalian sirt1 as a proviral factor for middle east respiratory syndrome coronavirus replication.viral proteins must intimately interact with the host cell machinery during virus replication. here, we used the yeast saccharomyces cerevisiae as a system to identify novel functional interactions between viral proteins and eukaryotic cells. our work demonstrates that when the middle east respiratory syndrome coronavirus (mers-cov) orf4a accessory gene is expressed in yeast it causes a slow-growth phenotype. orf4a has been characterized as an interferon antagonist in mammalian cells, and yet ye ...201931142674
bacterial outer membrane vesicles (omvs)-based dual vaccine for influenza a h1n1 virus and mers-cov.vaccination is the most functional medical intervention to prophylactically control severe diseases caused by human-to-human or animal-to-human transmissible viral pathogens. annually, seasonal influenza epidemics attack human populations leading to 290-650 thousand deaths/year worldwide. recently, a novel middle east respiratory syndrome coronavirus emerged. together, those two viruses present a significant public health burden in areas where they circulate. herein, we generated a bacterial out ...201931141982
middle east respiratory syndrome coronavirus in the last two years: health care workers still at risk.an important emerging respiratory virus is the middle east respiratory syndrome coronavirus (mers-cov). mers-cov had been associated with a high case fatality rate especially among severe cases.201931128983
human β-defensin 2 is involved in ccr2-mediated nod2 signal transduction, leading to activation of the innate immune response in macrophages.beta-defensins contribute to host innate defense against various pathogens, including viruses, although the details of their roles in innate immune cells are unclear. we previously reported that human β-defensin 2 (hbd 2) activates primary innate immunity against viral infection and suggested that it plays a role in the induction of the adaptive immune response. we analyzed the mechanisms by which hbd 2 primes innate antiviral immunity and polarized activation of macrophage-like thp-1 cells usin ...201931126693
middle east respiratory syndrome coronavirus (mers-cov) in oman: current situation and going forward. 201931110623
novel gold nanorod-based hr1 peptide inhibitor for middle east respiratory syndrome coronavirus.middle east respiratory syndrome coronavirus (mers-cov) causes a severe acute respiratory syndrome-like illness with high pathogenicity and mortality due to the lack of effective therapeutics. currently, only few antiviral agents are available for the treatment of mers, but their effects have been greatly impaired by low antiviral activity, poor metabolic stability, and serious adverse effects. therefore, the development of effective treatment for mers is urgently needed. in this study, a series ...201931099550
middle east respiratory syndrome coronavirus (mers-cov): infection, immunological response, and vaccine development.middle east respiratory syndrome coronavirus (mers-cov) first emerged in late 2012. since its emergence, a total of 2279 patients from 27 countries have been infected across the globe according to a world health organization (who) report (feb. 12th, 2019). approximately 806 patients have died. the virus uses its spike proteins as adhesive factors that are proinflammatory for host entry through a specific receptor called dipeptidyl peptidase-4 (dpp4). this receptor is considered a key factor in t ...201931089478
comparative analysis of eleven healthcare-associated outbreaks of middle east respiratory syndrome coronavirus (mers-cov) from 2015 to 2017.since its emergence in 2012, 2,260 cases and 803 deaths due to middle east respiratory syndrome coronavirus (mers-cov) have been reported to the world health organization. most cases were due to transmission in healthcare settings, sometimes causing large outbreaks. we analyzed epidemiologic and clinical data of laboratory-confirmed mers-cov cases from eleven healthcare-associated outbreaks in the kingdom of saudi arabia and the republic of korea between 2015-2017. we quantified key epidemiologi ...201931089148
development of label-free colorimetric assay for mers-cov using gold nanoparticles.worldwide outbreaks of infectious diseases necessitate the development of rapid and accurate diagnostic methods. colorimetric assays are a representative tool to simply identify the target molecules in specimens through color changes of an indicator (e.g., nanosized metallic particle, and dye molecules). the detection method is used to confirm the presence of biomarkers visually and measure absorbance of the colored compounds at a specific wavelength. in this study, we propose a colorimetric ass ...201931062580
mers-cov infection among healthcare workers and risk factors for death: retrospective analysis of all laboratory-confirmed cases reported to who from 2012 to 2 june 2018.approximately half of the reported laboratory-confirmed infections of middle east respiratory syndrome coronavirus (mers-cov) have occurred in healthcare settings, and healthcare workers constitute over one third of all secondary infections. this study aimed to describe secondary cases of mers-cov infection among healthcare workers and to identify risk factors for death.202031056437
influenza virus rna recovered from droplets and droplet nuclei emitted by adults in an acute care setting.transmission in hospital settings of seasonal influenza viruses and novel agents such as the middle east respiratory syndrome coronavirus (mers-cov) is well-described but poorly understood. the characterization of potentially infectious bio-aerosols in the healthcare setting remains an important yet ill-defined factor in the transmission of respiratory viruses. empiric data describing the distribution of bio-aerosols enable discernment of potential exposure risk to respiratory viruses. we sought ...201931050610
current epidemiological status of middle east respiratory syndrome coronavirus in the world from 1.1.2017 to 17.1.2018: a cross-sectional study.middle east respiratory syndrome coronavirus (mers-cov) is considered to be responsible for a new viral epidemic and an emergent threat to global health security. this study describes the current epidemiological status of mers-cov in the world.201931029095
diagnostic delays in middle east respiratory syndrome coronavirus patients and health systems.although middle east respiratory syndrome coronavirus (mers-cov) diagnostic delays remain a major challenge in health systems, the source of delays has not been recognized in the literature. the aim of this study is to quantify patient and health-system delays and to identify their associated factors.202031006635
risk factors for mers-cov seropositivity among animal market and slaughterhouse workers, abu dhabi, united arab emirates, 2014-2017.camel contact is a recognized risk factor for middle east respiratory syndrome coronavirus (mers-cov) infection. because specific camel exposures associated with mers-cov seropositivity are not fully understood, we investigated worker-camel interactions and mers-cov seroprevalence. we assessed worker seroprevalence in 2 slaughterhouses and 1 live-animal market in abu dhabi, united arab emirates, during 2014-2017 and administered an epidemiologic survey in 2016 and 2017. across 3 sampling rounds ...201931002068
emerging respiratory infections threatening public health in the asia-pacific region: a position paper of the asian pacific society of respirology.in past decades, we have seen several epidemics of respiratory infections from newly emerging viruses, most of which originated in animals. these emerging infections, including severe acute respiratory syndrome coronavirus (sars-cov), middle east respiratory syndrome coronavirus (mers-cov) and the pandemic influenza a(h1n1) and avian influenza (ai) viruses, have seriously threatened global health and the economy. in particular, mers-cov and ai a(h7n9) are still causing infections in several area ...201930985968
knowledge and practices of primary health care physicians regarding updated guidelines of mers-cov infection in abha city.human coronaviruses (hcov) usually cause mild to moderate upper respiratory tract illnesses. the novel coronavirus (ncov), or middle east respiratory syndrome coronavirus (mers-cov), is a particular strain different from any other known hcov with the possibility of human and also zoonotic transmissions. the aim of the study to assess primary health care (phc) physicians' knowledge and adherence regarding saudi ministry of health guidelines regarding mers-cov.201930984654
recent aspects on the pathogenesis mechanism, animal models and novel therapeutic interventions for middle east respiratory syndrome coronavirus infections.middle east respiratory syndrome coronavirus (mers-cov) is an emerging zoonotic virus considered as one of the major public threat with a total number of 2 298 laboratory-confirmed cases and 811 associated deaths reported by world health organization as of january 2019. the transmission of the virus was expected to be from the camels found in middle eastern countries via the animal and human interaction. the genome structure provided information about the pathogenicity and associated virulent fa ...201930984127
construction of lentivirus-based reference material for rt-pcr detection of middle east respiratory syndrome coronavirus and its application in external quality assessment.nucleic acid amplification technology (nat) has been the most used one for rapid detection of middle east respiratory syndrome coronavirus (mers-cov) since mers-cov was first detected in 2012. it is important to develop stable and safe reference materials for assessing the quality of nat kits and performing an external quality assessment (eqa) in different laboratories. in this study, the mers-cov rna fragments including upe, orf1b, and n were packed within human immunodeficiency virus type 1 (h ...201930961704
inevitable isolation and the change of stress markers in hemodialysis patients during the 2015 mers-cov outbreak in korea.during the outbreak of middle east respiratory syndrome coronavirus(mers-cov) in 2015, one hemodialysis patient was infected with mers-cov, and the remaining hemodialysis(hd) patients (n = 83) and medical staff (n = 12) had to undergo dialysis treatment in an isolated environment. this study was performed to investigate the effects of stress caused by dialysis treatment under isolation. plasma samples from the hd patients and medical staff were collected at the time of isolation(m0), the followi ...201930952879
evolutionary relationship analysis of middle east respiratory syndrome coronavirus 4a and 4b protein coding sequences.the 4a and 4b proteins of the middle east respiratory syndrome coronavirus (mers-cov) have been described for their antagonism on host innate immunity. however, unlike clustering patterns of the complete gene sequences of human and camel mers-covs, the 4a and 4b protein coding regions did not constitute species-specific phylogenetic groups. moreover, given the estimated evolutionary rates of the complete, 4a, and 4b gene sequences, the 4a and 4b proteins might be less affected by species-specifi ...201930944524
identification and design of novel small molecule inhibitors against mers-cov papain-like protease via high-throughput screening and molecular modeling.the development of new therapeutic agents against the coronavirus causing middle east respiratory syndrome (mers) is a continuing imperative. the initial mers-cov epidemic was contained entirely through public health measures, but episodic cases continue, as there are currently no therapeutic agents effective in the treatment of mers-cov, although multiple strategies have been proposed. in this study, we screened 30,000 compounds from three different compound libraries against one of the essenti ...201930940566
migrating a lab-developed mers-cov real-time pcr to 3 "sample to result" systems: experiences on optimization and validation.the goal of the study was to adapt our middle east respiratory syndrome coronavirus (mers-cov) lab-developed test (ldt) to 3 "sample to result" (s2r) systems: bd max (bd), elite ingenius (elitechgroup), and aries (luminex). the bd max and ingenius system allowed use of lab-developed primers and taqman probes, while aries required conversion to multicode primers for melting curve analysis. each device required ≤1 day of training and assay optimization. no discordant results were noted after analy ...201930929995
3-trifluoromethylpyrazolones derived nucleosides: synthesis and antiviral evaluation.dengue (denv) viral infection is a global public health problem that infrequently develops life threatening diseases such as dengue hemorrhagic fever (dfs) and dengue shock syndrome (dss). middle east respiratory syndrome coronavirus (mers-cov) is a highly pathogenic human corona virus with 38% fatality rate of infected patients. a series of 4-arylhydrazono-5-trifluoromethyl-pyrazolones, their ribofuranosyl, and 5'-deoxyribofuranosyl nucleosides were synthesized, geometry optimized using density ...201930929566
a highly immunogenic, protective, and safe adenovirus-based vaccine expressing middle east respiratory syndrome coronavirus s1-cd40l fusion protein in a transgenic human dipeptidyl peptidase 4 mouse model.infection control measures have played a major role in limiting human/camel-to-human transmission of middle east respiratory syndrome coronavirus (mers-cov); however, development of effective and safe human or camel vaccines is warranted.201930911758
comparative serological study for the prevalence of anti-mers coronavirus antibodies in high- and low-risk groups in qatar.infection with middle east respiratory syndrome coronavirus (mers-cov) could be asymptomatic or cause mild influenza-like illness. therefore, the prevalence of mers-cov infections in the general population could be underestimated, which necessitates active surveillance to determine the epidemiological importance of asymptomatic cases. the aim of this study is to evaluate the performance of various serological assays and to estimate the seroprevalence of anti-mers-cov antibodies in high- and low- ...201930906787
sequential emergence and wide spread of neutralization escape middle east respiratory syndrome coronavirus mutants, south korea, 2015.the unexpectedly large outbreak of middle east respiratory syndrome in south korea in 2015 was initiated by an infected traveler and amplified by several "superspreading" events. previously, we reported the emergence and spread of mutant middle east respiratory syndrome coronavirus bearing spike mutations (i529t or d510g) with reduced affinity to human receptor cd26 during the outbreak. to assess the potential association of spike mutations with superspreading events, we collected virus genetic ...201930900977
the perceived effectiveness of mers-cov educational programs and knowledge transfer among primary healthcare workers: a cross-sectional survey.knowledge transfer of middle east respiratory syndrome coronavirus (mers-cov) involves the dissemination of created/acquired information on mers-cov in hospitals, making this information accessible to all healthcare workers (hcws). this study evaluated the perceived effectiveness of mers-cov educational programs and knowledge transfer among primary care hcws at a hospital in saudi arabia that witnessed the largest outbreak of confirmed mers-cov cases in this country.201930898086
production of pseudotyped particles to study highly pathogenic coronaviruses in a biosafety level 2 setting.the protocol aims to generate coronavirus (cov) spike (s) fusion protein pseudotyped particles with a murine leukemia virus (mlv) core and luciferase reporter, using a simple transfection procedure of the widely available hek-293t cell line. once formed and released from producer cells, these pseudovirions incorporate a luciferase reporter gene. since they only contain the heterologous coronavirus spike protein on their surface, the particles behave like their native coronavirus counterparts for ...201930882796
middle east respiratory syndrome coronavirus infection dynamics and antibody responses among clinically diverse patients, saudi arabia.middle east respiratory syndrome coronavirus (mers-cov) shedding and antibody responses are not fully understood, particularly in relation to underlying medical conditions, clinical manifestations, and mortality. we enrolled mers-cov-positive patients at a hospital in saudi arabia and periodically collected specimens from multiple sites for real-time reverse transcription pcr and serologic testing. we conducted interviews and chart abstractions to collect clinical, epidemiologic, and laboratory ...201930882305
clinical predictors of mortality of middle east respiratory syndrome coronavirus (mers-cov) infection: a cohort study.since the emergence of the middle east respiratory syndrome coronavirus (mers-cov) in 2012, the virus had caused a high case fatality rate. the clinical presentation of mers varied from asymptomatic to severe bilateral pneumonia, depending on the case definition and surveillance strategies. there are few studies examining the mortality predictors in this disease. in this study, we examined clinical predictors of mortality of middle east respiratory syndrome (mers) infection.202030872071
broad-spectrum coronavirus antiviral drug discovery.the highly pathogenic coronaviruses severe acute respiratory syndrome coronavirus (sars-cov) and middle east respiratory syndrome coronavirus (mers-cov) are lethal zoonotic viruses that have emerged into human populations these past 15 years. these coronaviruses are associated with novel respiratory syndromes that spread from person-to-person via close contact, resulting in high morbidity and mortality caused by the progression to acute respiratory distress syndrome (ards). areas covered: the ri ...201930849247
correction to: genetic evidence of middle east respiratory syndrome coronavirus (mers-cov) and widespread seroprevalence among camels in kenya.the acknowledgement section in the original article was published incorrectly.201930820836
dampened nlrp3-mediated inflammation in bats and implications for a special viral reservoir host.bats are special in their ability to host emerging viruses. as the only flying mammal, bats endure high metabolic rates yet exhibit elongated lifespans. it is currently unclear whether these unique features are interlinked. the important inflammasome sensor, nlr family pyrin domain containing 3 (nlrp3), has been linked to both viral-induced and age-related inflammation. here, we report significantly dampened activation of the nlrp3 inflammasome in bat primary immune cells compared to human or mo ...201930804542
survey on implementation of one health approach for mers-cov preparedness and control in gulf cooperation council and middle east countries.in 2015, a one health working group was established in qatar to conduct a survey in the gulf cooperation council countries, egypt, and jordan to monitor preparedness of public health and veterinary health authorities in response to the middle east respiratory syndrome coronavirus epidemic. all but 1 country indicated they established joint one health policy teams for investigation and response. however, the response to the questionnaires was largely limited to veterinary authorities. critical ba ...201930789338
absence of neutralizing activity in serum 1 year after successful treatment with antivirals and recovery from mers in south korea.we evaluated the neutralizing activity in serum from three patients >1 year after recovery from middle east respiratory syndrome (mers) associated with mild pneumonia treated with antivirals during the mers outbreak in south korea at 2015. the neutralizing activity in serum was measured by pseudovirus inhibition assays. three-fold diluted serum of subjects showed only 9.7%, 10.3%, and 2.2% reductions in relative light units. so, significant neutralizing activity was not demonstrated in any sera ...201930775355
genetic characterization of middle east respiratory syndrome coronavirus, south korea, 2018.we evaluated genetic variation in middle east respiratory syndrome coronavirus (mers-cov) imported to south korea in 2018 using specimens from a patient and isolates from infected caco-2 cells. the mers-cov strain in this study was genetically similar to a strain isolated in riyadh, saudi arabia, in 2017.201930753126
mers-cov, influenza and other respiratory viruses among symptomatic pilgrims during 2014 hajj season.more than two million muslims visit makkah, saudi arabia, annually to perform the religious rituals of hajj where the risk of spreading respiratory infections is very common. the aim here was to screen symptomatic pilgrims for middle east respiratory syndrome coronavirus (mers-cov) and other viral etiologies. thus, 132 nasopharyngeal samples were collected from pilgrims presenting with acute respiratory symptoms at the healthcare facilities in the holy sites during the 5 days of the 2014 hajj se ...201930729547
international biological reference preparations for epidemic infectious diseases.recent years have seen unprecedented investment in research and development for countermeasures for high-threat pathogens, including specific and ambitious objectives for development of diagnostics, therapeutics, and vaccines. the inadequate availability of biological reference materials for these pathogens poses a genuine obstacle in pursuit of these objectives, and the lack of a comprehensive and equitable framework for developing reference materials is a weakness. we outline the need for inte ...201930666925
middle east respiratory syndrome vaccine candidates: cautious optimism.efforts towards developing a vaccine for middle east respiratory syndrome coronavirus (mers-cov) have yielded promising results. utilizing a variety of platforms, several vaccine approaches have shown efficacy in animal models and begun to enter clinical trials. in this review, we summarize the current progress towards a mers-cov vaccine and highlight potential roadblocks identified from previous attempts to generate coronavirus vaccines.201930658390
characterization of the lipidomic profile of human coronavirus-infected cells: implications for lipid metabolism remodeling upon coronavirus replication.lipids play numerous indispensable cellular functions and are involved in multiple steps in the replication cycle of viruses. infections by human-pathogenic coronaviruses result in diverse clinical outcomes, ranging from self-limiting flu-like symptoms to severe pneumonia with extrapulmonary manifestations. understanding how cellular lipids may modulate the pathogenicity of human-pathogenic coronaviruses remains poor. to this end, we utilized the human coronavirus 229e (hcov-229e) as a model cor ...201930654597
potent mers-cov fusion inhibitory peptides identified from hr2 domain in spike protein of bat coronavirus hku4.the middle east respiratory syndrome coronavirus (mers-cov) emerged in 2012 and caused continual outbreaks worldwide with high mortality. however, no effective anti-mers-cov drug is currently available. recently, numerous evolutionary studies have suggested that mers-cov originated from bat coronavirus (batcov). we herein reported that three peptides derived from the hr2 region in spike protein of batcov hku4, including hku4-hr2p1, hku4-hr2p2 and hku4-hr2p3, could bind the mers-cov hr1-derived p ...201930646495
structure and oligomerization state of the c-terminal region of the middle east respiratory syndrome coronavirus nucleoprotein.middle east respiratory syndrome coronavirus (mers-cov) is a human pathogen responsible for a severe respiratory illness that emerged in 2012. structural information about the proteins that constitute the viral particle is scarce. in order to contribute to a better understanding of the nucleoprotein (n) in charge of rna genome encapsidation, the structure of the c-terminal domain of n from mers-cov obtained using single-crystal x-ray diffraction is reported here at 1.97 å resolution. the molecul ...201930644840
complement receptor c5ar1 inhibition reduces pyroptosis in hdpp4-transgenic mice infected with mers-cov.middle east respiratory syndrome coronavirus (mers-cov) is a highly pathogenic virus with a crude mortality rate of ~35%. previously, we established a human dpp4 transgenic (hdpp4-tg) mouse model in which we studied complement overactivation-induced immunopathogenesis. here, to better understand the pathogenesis of mers-cov, we studied the role of pyroptosis in thp-1 cells and hdpp4 tg mice with mers-cov infection. we found that mers-cov infection induced pyroptosis and over-activation of comple ...201930634407
srebp-dependent lipidomic reprogramming as a broad-spectrum antiviral target.viruses are obligate intracellular microbes that exploit the host metabolic machineries to meet their biosynthetic demands, making these host pathways potential therapeutic targets. here, by exploring a lipid library, we show that am580, a retinoid derivative and rar-α agonist, is highly potent in interrupting the life cycle of diverse viruses including middle east respiratory syndrome coronavirus and influenza a virus. using click chemistry, the overexpressed sterol regulatory element binding p ...201930631056
acute respiratory infection in human dipeptidyl peptidase 4-transgenic mice infected with middle east respiratory syndrome coronavirus.middle east respiratory syndrome coronavirus (mers-cov) infection can manifest as a mild illness, acute respiratory distress, organ failure, or death. several animal models have been established to study disease pathogenesis and to develop vaccines and therapeutic agents. here, we developed transgenic (tg) mice on a c57bl/6 background; these mice expressed human cd26/dipeptidyl peptidase 4 (hdpp4), a functional receptor for mers-cov, under the control of an endogenous hdpp4 promoter. we then cha ...201930626685
combining a fusion inhibitory peptide targeting the mers-cov s2 protein hr1 domain and a neutralizing antibody specific for the s1 protein receptor-binding domain (rbd) showed potent synergism against pseudotyped mers-cov with or without mutations in rbd.middle east respiratory syndrome coronavirus (mers-cov) has continuously posed a threat to public health worldwide, yet no therapeutics or vaccines are currently available to prevent or treat mers-cov infection. we previously identified a fusion inhibitory peptide (hr2p-m2) targeting the mers-cov s2 protein hr1 domain and a highly potent neutralizing monoclonal antibody (m336) specific to the s1 spike protein receptor-binding domain (rbd). however, m336 was found to have reduced efficacy against ...201930621343
an atypical case of middle east respiratory syndrome in a returning traveler to korea from kuwait, 2018.we report a case of middle east respiratory syndrome coronavirus (mers-cov) infection in a 61-year-old businessman returning from kuwait. the patient arrived there on august 16, 2018, developed watery diarrhea on august 28 (day 0), and came back to korea on september 7 (day 10) as his condition worsened. upon arrival, he complained of diarrhea and weakness, but denied any respiratory symptoms, and he directly went to visit an emergency room. chest radiography revealed interstitial infiltrates in ...201830595687
scope and extent of healthcare-associated middle east respiratory syndrome coronavirus transmission during two contemporaneous outbreaks in riyadh, saudi arabia, 2017.to investigate a middle east respiratory syndrome coronavirus (mers-cov) outbreak event involving multiple healthcare facilities in riyadh, saudi arabia; to characterize transmission; and to explore infection control implications.201930595141
clinical and laboratory findings of middle east respiratory syndrome coronavirus infection.there is a paucity of data regarding the differentiating characteristics of patients with laboratory-confirmed and those negative for middle east respiratory syndrome coronavirus (mers-cov) in south korea. this hospital-based retrospective study compared mers-cov-positive and mers-cov-negative patients. a total of seven positive patients and 55 negative patients with a median age of 43 years (p = 0.845) were included. no statistical differences were observed with respect to their sex and the pre ...201930584196
individual and network characteristic associated with hospital-acquired middle east respiratory syndrome coronavirus.during outbreaks of infectious diseases, transmission of the pathogen can form networks of infected individuals connected either directly or indirectly.202030578142
identification and characterization of coronaviridae genomes from vietnamese bats and rats based on conserved protein domains.the coronaviridae family of viruses encompasses a group of pathogens with a zoonotic potential as observed from previous outbreaks of the severe acute respiratory syndrome coronavirus and middle east respiratory syndrome coronavirus. accordingly, it seems important to identify and document the coronaviruses in animal reservoirs, many of which are uncharacterized and potentially missed by more standard diagnostic assays. a combination of sensitive deep sequencing technology and computational algo ...201830568804
development of small-molecule mers-cov inhibitors.middle east respiratory syndrome coronavirus (mers-cov) with potential to cause global pandemics remains a threat to the public health, security, and economy. in this review, we focus on advances in the research and development of small-molecule mers-cov inhibitors targeting different stages of the mers-cov life cycle, aiming to prevent or treat mers-cov infection.201830562987
asymptomatic middle east respiratory syndrome coronavirus (mers-cov) infection: extent and implications for infection control: a systematic review.the middle east respiratory syndrome coronavirus (mers-cov) emerged in 2012 and attracted an international attention as the virus caused multiple healthcare associated outbreaks. there are reports of the role of asymptomatic individuals in the transmission of mers-cov, however, the exact role is not known.202030550839
structural basis of development of multi-epitope vaccine against middle east respiratory syndrome using in silico approach.middle east respiratory syndrome (mers) is caused by mers coronavirus (mers-cov). thus far, mers outbreaks have been reported from saudi arabia (2013 and 2014) and south korea (2015). no specific vaccine has yet been reported against mers.201830538505
evaluation of preparedness of healthcare student volunteers against middle east respiratory syndrome coronavirus (mers-cov) in makkah, saudi arabia: a cross-sectional study.to assess the knowledge and attitude of senior medical, dental, nursing and pharmacy students toward middle east respiratory syndrome-corona virus (mers-cov) in saudi arabia.201830533343
co-localization of middle east respiratory syndrome coronavirus (mers-cov) and dipeptidyl peptidase-4 in the respiratory tract and lymphoid tissues of pigs and llamas.this study investigated the co-localization of the middle east respiratory syndrome coronavirus (mers-cov) and its receptor dipeptidyl peptidase-4 (dpp4) by immunohistochemistry (ihc) across respiratory and lymphoid organs of experimentally mers-cov infected pigs and llamas. also, scanning electron microscopy was performed to assess the ciliary integrity of respiratory epithelial cells in both species. in pigs, on day 2 post-inoculation (p.i.), dpp4-mers-cov co-localization was detected in media ...201930520548
middle east respiratory syndrome coronavirus (mers-cov): impact on saudi arabia, 2015.middle east respiratory syndrome is the acute respiratory syndrome caused by betacoronavirus mers-cov. the first case of this disease was reported from saudi arabia in 2012. this virus is lethal and is a close relative of a severe acute respiratory syndrome (sars), which is responsible for more than 3000 deaths in 2002-2003. according to ministry of health, saudi arabia. the number of new cases is 457 in 2015. riyadh has the highest number of reports in comparison to the other cities. according ...201830505188
infection control influence of middle east respiratory syndrome coronavirus: a hospital-based analysis.middle east respiratory syndrome coronavirus (mers-cov) caused multiple outbreaks. such outbreaks increase economic and infection control burdens. we studied the infection control influence of mers-cov using a hospital-based analysis.201930502108
neutralizing monoclonal antibodies as promising therapeutics against middle east respiratory syndrome coronavirus infection.since emerging in 2012, middle east respiratory syndrome coronavirus (mers-cov) has been a global public health threat with a high fatality rate and worldwide distribution. there are no approved vaccines or therapies for mers until now. passive immunotherapy with neutralizing monoclonal antibodies (mabs) is an effective prophylactic and therapeutic reagent against emerging viruses. in this article, we review current advances in neutralizing mabs against mers-cov. the receptor-binding domain (rbd ...201830513619
a high-throughput inhibition assay to study mers-cov antibody interactions using image cytometry.the emergence of new pathogens, such as middle east respiratory syndrome coronavirus (mers-cov), poses serious challenges to global public health and highlights the urgent need for methods to rapidly identify and characterize potential therapeutic or prevention options, such as neutralizing antibodies. spike (s) proteins are present on the surface of mers-cov virions and mediate viral entry. s is the primary target for mers-cov vaccine and antibody development, and it has become increasingly imp ...201930468747
critically ill healthcare workers with the middle east respiratory syndrome (mers): a multicenter study.middle east respiratory syndrome coronavirus (mers-cov) leads to healthcare-associated transmission to patients and healthcare workers with potentially fatal outcomes.201830439974
respiratory viruses in returning hajj & umrah pilgrims with acute respiratory illness in 2014-2015.respiratory tract infections are common among hajj and umrah pilgrims which pose a public health risk of spread of respiratory infections. influenza has been reported from indian hajj and umrah returning pilgrims, but data on other respiratory pathogens are sparse in india. here we report the presence of common respiratory viral pathogens in returning hajj and umrah pilgrims suffering from acute respiratory illness (ari) in 2014-2015.201830425224
mutations in the spike protein of middle east respiratory syndrome coronavirus transmitted in korea increase resistance to antibody-mediated neutralization.middle east respiratory syndrome coronavirus (mers-cov) poses a threat to public health. the virus is endemic in the middle east but can be transmitted to other countries by travel activity. the introduction of mers-cov into the republic of korea by an infected traveler resulted in a hospital outbreak of mers that entailed 186 cases and 38 deaths. the mers-cov spike (s) protein binds to the cellular protein dpp4 via its receptor binding domain (rbd) and mediates viral entry into target cells. du ...201930404801
highly infectious diseases in the mediterranean sea area: inventory of isolation capabilities and recommendations for appropriate isolation.epidemics such as viral haemorrhagic fevers, severe acute respiratory syndrome, middle east respiratory syndrome coronavirus or yet unknown ones have few chances of disappearing. globalization, worldwide travel, climate change, social conflicts and wars, among others, are likely to favor the emergence of epidemics. preparedness of hospitals to prevent the spread of these outbreaks is among the prioritized political programmes of many countries. the euronhid network has in the past drawn a map of ...201830402245
prevalence of comorbidities in cases of middle east respiratory syndrome coronavirus: a retrospective study.the middle east respiratory syndrome coronavirus (mers-cov) is a life-threatening respiratory disease with a high case fatality rate; however, its risk factors remain unclear. we aimed to explore the influence of demographic factors, clinical manifestations and underlying comorbidities on mortality in mers-cov patients. retrospective chart reviews were performed to identify all laboratory-confirmed cases of mers-cov infection in saudi arabia that were reported to the ministry of health of saudi ...201830394248
significant spike-specific igg and neutralizing antibodies in mice induced by a novel chimeric virus-like particle vaccine candidate for middle east respiratory syndrome coronavirus. 201830374826
generation and characterization of a monoclonal antibody against mers-cov targeting the spike protein using a synthetic peptide epitope-cpg-dna-liposome complex.middle east respiratory syndrome coronavirus (mers-cov) uses the spike (s) glycoprotein to recognize and enter target cells. in this study, we selected two epitope peptide sequences within the receptor binding domain (rbd) of the mers-cov s protein. we used a complex consisting of the epitope peptide of the mers-cov s protein and cpg-dna encapsulated in liposome complex to immunize mice, and produced the monoclonal antibodies 506-2g10g5 and 492-1g10e4e2. the western blotting data showed that bot ...201930355437
middle east respiratory syndrome coronavirus intermittent positive cases: implications for infection control.middle east respiratory syndrome coronavirus (mers-cov) continues to be reported from the kingdom of saudi arabia. data on the phenomenon of intermittent positive results for mers-cov on reverse-transcription polymerase chain reaction (rt-pcr) with negative results in between are lacking. here we describe cases with intermittent positive mers-cov test results and highlight the required number of tests to rule out or rule in mers-cov infection based on a large retrospective cohort of patients wit ...201930352694
psychological impact of the 2015 mers outbreak on hospital workers and quarantined hemodialysis patients.this study aimed to assess the immediate stress and psychological impact experienced by quarantined patients undergoing hemodialysis and university hospital workers who treated patients middle east respiratory syndrome (mers) during its outbreak.201830343247
comparison of perceived and observed hand hygiene compliance in healthcare workers in mers-cov endemic regions.this study investigated healthcare workers' perceptions of hand hygiene practices by comparing personal reports, as assessed by questionnaires, to direct observations of the workers' hand hygiene practices. the study employed a cross-sectional research design. observations were made using a 16-item checklist, based on three sources: centers for disease control and prevention (cdc), world health organization (who), and boyce and pittet's guidelines of hand hygiene. the checklist was used for both ...201830301272
infectious mers-cov isolated from a mildly ill patient, saudi arabia.middle east respiratory syndrome coronavirus (mers-cov) is associated with a wide range of clinical presentations, from asymptomatic or mildly ill to severe respiratory illness including death. we describe isolation of infectious mers-cov from the upper respiratory tract of a mildly ill 27-year-old female in saudi arabia 15 days after illness onset.201830294617
multihospital outbreak of a middle east respiratory syndrome coronavirus deletion variant, jordan: a molecular, serologic, and epidemiologic investigation.an outbreak of middle east respiratory syndrome coronavirus (mers-cov) in jordan in 2015 involved a variant virus that acquired distinctive deletions in the accessory open reading frames. we conducted a molecular and seroepidemiologic investigation to describe the deletion variant's transmission patterns and epidemiology.201830294616
temporal dynamics of middle east respiratory syndrome coronavirus in the arabian peninsula, 2012-2017.middle east respiratory syndrome coronavirus (mers-cov) remains a notable disease and poses a significant threat to global public health. the arabian peninsula is considered a major global epicentre for the disease and the virus has crossed regional and continental boundaries since 2012. in this study, we focused on exploring the temporal dynamics of mers-cov in human populations in the arabian peninsula between 2012 and 2017, using publicly available data on case counts and combining two analyt ...201830293534
clinical implication of radiographic scores in acute middle east respiratory syndrome coronavirus pneumonia: report from a single tertiary-referral center of south korea.the aim of this study is to determine the earliest cutoff of radiographic score as a potential prognostic indicator of fatal outcomes in patients with acute middle east respiratory syndrome coronavirus (mers-cov) pneumonia. the institutional review board approved this retrospective study. serial chest radiographies (cxrs) were obtained from viral exposure until death or discharge in 35 patients with laboratory confirmed mers-cov infection. radiographic scores were calculated by multiplying a fou ...201830292266
assessment of fever in the returning traveller.evaluation of people returning from trips abroad with fever is an important skill for all general physicians given the increasing trend in foreign travel. this evaluation should comprise a detailed travel history, thorough clinical examination, appropriate initial tests and a knowledge of when to ask for further advice. an understanding of the incubation periods of common imported infections and a syndromic approach to patients' symptoms is helpful in order to narrow down the likely diagnosis. t ...201830290751
atypical presentation of middle east respiratory syndrome coronavirus in a lebanese patient returning from saudi arabia.around 2090 confirmed cases of middle east respiratory syndrome coronavirus (mers-cov) from 27 countries have been reported to the world health organization (who) between september 2012 and october 2017, the majority of whom occurring in countries in the arabian peninsula, mainly in saudi arabia. mers- cov can have atypical and misleading presentations resulting in delays in diagnosis and is associated with a high mortality rate especially in elderly patients with multiple comorbidities. herein, ...201831999642
lysosomal proteases are a determinant of coronavirus tropism.cell entry by coronaviruses involves two principal steps, receptor binding and membrane fusion; the latter requires activation by host proteases, particularly lysosomal proteases. despite the importance of lysosomal proteases in both coronavirus entry and cell metabolism, the correlation between lysosomal proteases and cell tropism of coronaviruses has not been established. here, we examined the roles of lysosomal proteases in activating coronavirus surface spike proteins for membrane fusion, us ...201830258004
elevated human dipeptidyl peptidase 4 expression reduces the susceptibility of hdpp4 transgenic mice to middle east respiratory syndrome coronavirus infection and disease.the ongoing middle east respiratory syndrome coronavirus (mers-cov) infections pose threats to public health worldwide, making an understanding of mers pathogenesis and development of effective medical countermeasures (mcms) urgent.201930256968
human coronavirus infections in israel: epidemiology, clinical symptoms and summer seasonality of hcov-hku1.human coronaviruses (hcovs) cause mild to severe respiratory diseases. six types of hcovs have been discovered, the most recent one termed the middle east respiratory syndrome coronavirus (mers-cov). the aim of this study is to monitor the circulation of hcov types in the population during 2015⁻2016 in israel. hcovs were detected by real-time pcr analysis in 1910 respiratory samples, collected from influenza-like illness (ili) patients during the winter sentinel influenza survey across israel. m ...201830241410
post-exposure prophylaxis for middle east respiratory syndrome in healthcare workers.an effective post-exposure prophylaxis (pep) strategy may limit the spread of infection. however, there is no consensus regarding pep for middle east respiratory syndrome coronavirus (mers-cov) infection. this study assessed the efficacy of ribavirin and lopinavir/ritonavir as pep for healthcare workers (hcws) exposed to patients with severe mers-cov pre-isolation pneumonia. the safety of the pep regimen was assessed. hcws with high-risk exposure to mers-cov pre-isolation pneumonia were retrospe ...201930240813
evaluation of visual triage for screening of middle east respiratory syndrome coronavirus patients.the emergence of middle east respiratory syndrome coronavirus (mers-cov) in september 2012 in saudi arabia had attracted the attention of the global health community. in 2017 the saudi ministry of health released a visual triage system with scoring to alert healthcare workers in emergency departments (eds) and haemodialysis units for the possibility of occurrence of mers-cov infection. we performed a retrospective analysis of this visual score to determine its sensitivity and specificity. the st ...201830224971
lack of seasonal variation of middle east respiratory syndrome coronavirus (mers-cov). 202030218713
de novo design of α-helical lipopeptides targeting viral fusion proteins: a promising strategy for relatively broad-spectrum antiviral drug discovery.class i enveloped viruses share similarities in their apparent use of a hexameric coiled-coil assembly to drive the merging of virus and host cell membranes. inhibition of coiled coil-mediated interactions using bioactive peptides that replicate an α-helical chain from the viral fusion machinery has significant antiviral potential. here, we present the construction of a series of lipopeptides composed of a de novo heptad repeat sequence-based α-helical peptide plus a hydrocarbon tail. promisingl ...201830192544
screening for middle east respiratory syndrome coronavirus among febrile indonesian hajj pilgrims: a study on 28,197 returning pilgrims.there were 211,000 indonesian hajj pilgrims going to mecca through 11 main airports in 2015 who were at risk of contracting the middle east respiratory syndrome coronavirus (mers-cov). we aimed to find out whether there was any occurrence of mers-cov by performing screening on 28,197 returning pilgrims. those with a body temperature of > 38 °c and respiratory symptoms were sent to the airport clinic to have an oropharyngeal swab and a bacterial culture. fifteen pilgrims had fever (> 38 °c) accom ...201830159042
a screening campaign in sea urchin egg homogenate as a platform for discovering modulators of naadp-dependent ca2+ signaling in human cells.the ca2+ mobilizing second messenger nicotinic acid adenine dinucleotide phosphate (naadp) regulates intracellular trafficking events, including translocation of certain enveloped viruses through the endolysosomal system. targeting naadp-evoked ca2+ signaling may therefore be an effective strategy for discovering novel antivirals as well as therapeutics for other disorders. to aid discovery of novel scaffolds that modulate naadp-evoked ca2+ signaling in human cells, we have investigated the pote ...201830145428
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