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development of a recombinant replication-deficient rabies virus-based bivalent-vaccine against mers-cov and rabies virus and its humoral immunogenicity in mice.middle east respiratory syndrome-coronavirus (mers-cov) is an emerging virus that causes severe disease with fatal outcomes; however, there are currently no approved vaccines or specific treatments against mers-cov. here, we developed a novel bivalent vaccine against mers-cov and rabies virus (rv) using the replication-incompetent p-gene-deficient rv (rvδp), which has been previously established as a promising and safe viral vector. mers-cov spike glycoprotein comprises s1 and s2 subunits, with ...201931589656
evaluating the potential impact of targeted vaccination strategies against severe acute respiratory syndrome coronavirus (sars-cov) and middle east respiratory syndrome coronavirus (mers-cov) outbreaks in the healthcare setting.severe acute respiratory syndrome (sars) and middle east respiratory syndrome (mers) are two coronaviruses with demonstrated potential to generate significant nosocomial outbreaks. in particular, mers continues to pose a significant threat in the middle east since 2012. currently, no licensed vaccine or drug treatment is available to treat patients infected with either coronavirus. however, there are some mers vaccines in the preclinical stage of development. we sought to evaluate the potential ...201931587665
estimation of direct medical costs of middle east respiratory syndrome coronavirus infection: a single-center retrospective chart review study.among the countries affected by middle east respiratory syndrome (mers), saudi arabia was impacted the most, with 2,058 cases reported as of june 2019. however, the impact of the mers epidemic on the saudi economy is unknown.201931819541
viromimetic sting agonist-loaded hollow polymeric nanoparticles for safe and effective vaccination against middle east respiratory syndrome coronavirus.the continued threat of emerging, highly lethal infectious pathogens such as middle east respiratory syndrome coronavirus (mers-cov) calls for the development of novel vaccine technology that offers safe and effective prophylactic measures. here, a novel nanoparticle vaccine is developed to deliver subunit viral antigens and sting agonists in a virus-like fashion. sting agonists are first encapsulated into capsid-like hollow polymeric nanoparticles, which show multiple favorable attributes, incl ...201932313544
skp2 attenuates autophagy through beclin1-ubiquitination and its inhibition reduces mers-coronavirus infection.autophagy is an essential cellular process affecting virus infections and other diseases and beclin1 (becn1) is one of its key regulators. here, we identified s-phase kinase-associated protein 2 (skp2) as e3 ligase that executes lysine-48-linked poly-ubiquitination of becn1, thus promoting its proteasomal degradation. skp2 activity is regulated by phosphorylation in a hetero-complex involving fkbp51, phlpp, akt1, and becn1. genetic or pharmacological inhibition of skp2 decreases becn1 ubiquitina ...201931852899
middle east respiratory syndrome coronavirus in pediatrics: a report of seven cases from saudi arabia.infection with middle east respiratory syndrome coronavirus (mers-cov) emerged in 2012 as an important respiratory disease with high fatality rates of 40%-60%. despite the increased number of cases over subsequent years, the number of pediatric cases remained low. a review of studies conducted from june 2012 to april 19, 2016 reported 31 pediatric mers-cov cases. in this paper, we present the clinical and laboratory features of seven patients with pediatric mers. five patients had no underlying ...201929623560
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
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
lead molecule prediction and characterization for designing mers-cov 3c-like protease inhibitors: an in silico approach.3c-like protease also called the main protease is an essential enzyme for the completion of the life cycle of middle east respiratory syndrome coronavirus. in our study we predicted compounds which are capable of inhibiting 3c-like protease, and thus inhibit the lifecycle of middle east respiratory syndrome coronavirus using in silico methods.201929956635
middle east respiratory syndrome coronavirus (mers-cov) infection during pregnancy: report of two cases & review of the literature. 201929907538
serologic follow-up of middle east respiratory syndrome coronavirus cases and contacts-abu dhabi, united arab emirates.although there is evidence of person-to-person transmission of middle east respiratory syndrome coronavirus (mers-cov) in household and healthcare settings, more data are needed to describe and better understand the risk factors and transmission routes in both settings, as well as the extent to which disease severity affects transmission.201929905769
healthcare-associated infections: the hallmark of middle east respiratory syndrome coronavirus with review of the literature.middle east respiratory syndrome coronavirus (mers-cov) is capable of causing acute respiratory illness. laboratory-confirmed mers-cov cases may be asymptomatic, have mild disease, or have a life-threatening infection with a high case fatality rate. there are three patterns of transmission: sporadic community cases from presumed non-human exposure, family clusters arising from contact with an infected family index case, and healthcare-acquired infections among patients and from patients to healt ...201929864486
phylogenetic diversity and dna barcoding of the camel tick hyalomma dromedarii (acari: ixodidae) of the eastern region of saudi arabia.hard ticks are causative agents of physical illness and vectors of important diseases of human and livestock. the hard tick hyalomma dromedarii koch, 1844 is a major ectoparasite of livestock in the kingdom of saudi arabia (ksa), of which, the onehumped dromedaries camelus dromedarius is the most economically and culturally important and a potential reservoir of middle east respiratory syndrome coronavirus (merscov) disease. here we report on the molecular phylogenetic diversity of h. dromedarii ...201933597400
discovery and characterization of novel bat coronavirus lineages from kazakhstan.coronaviruses are positive-stranded rna viruses that infect a variety of hosts, resulting in a range of symptoms from gastrointestinal illness to respiratory distress. bats are reservoirs for a high diversity of coronaviruses, and focused surveillance detected several strains genetically similar to mers-coronavirus, sars-coronavirus, and the human coronaviruses 229e and nl63. the bat fauna of central asia, which link china to eastern europe, are relatively less studied than other regions of the ...201930999711
case report: detection of the middle east respiratory syndrome corona virus (mers-cov) in nasal secretions of a dead human.the middle east respiratory syndrome coronavirus (mers-cov) has been recognized as a highly pathogenic virus that infects the human respiratory tract and has high morbidity and mortality. the mers-cov is a huge burden on saudi arabian health-care facilities, causing approximately 40% mortality. the transmission mechanism of the virus is still not well understood. therefore, the prevention of any route of transmission is the best measure to arrest the spread of this disease. using the real time p ...201831435338
a novel role for cd26/dipeptidyl peptidase iv as a therapeutic target.cd26 is a 110 kda surface glycoprotein with intrinsic dipeptidyl peptidase iv activity that is expressed on numerous cell types and has a multitude of biological functions. the role of cd26 in immune regulation has been extensively characterized, with recent findings elucidating its linkage with signaling pathways and structures involved in t-lymphocyte activation as well as antigen presenting cell-t-cell interaction. in this paper, we will review emerging data on cd26-mediated immune regulation ...201829772527
development of fluorescent reverse transcription loop-mediated isothermal amplification (rt-lamp) using quenching probes for the detection of the middle east respiratory syndrome coronavirus.clinical detection of middle east respiratory syndrome (mers) coronavirus (mers-cov) in patients is achieved using genetic diagnostic methods, such as real-time rt-pcr assay. previously, we developed a reverse transcription-loop-mediated isothermal amplification (rt-lamp) assay for the detection of mers-cov [virol j. 2014. 11:139]. generally, amplification of rt-lamp is monitored by the turbidity induced by precipitation of magnesium pyrophosphate with newly synthesized dna. however, this mechan ...201829763640
radiographic and ct features of viral pneumonia.viruses are the most common causes of respiratory infection. the imaging findings of viral pneumonia are diverse and overlap with those of other nonviral infectious and inflammatory conditions. however, identification of the underlying viral pathogens may not always be easy. there are a number of indicators for identifying viral pathogens on the basis of imaging patterns, which are associated with the pathogenesis of viral infections. viruses in the same viral family share a similar pathogenesis ...201829757717
replicative virus shedding in the respiratory tract of patients with middle east respiratory syndrome coronavirus infection.information on the duration of replicative middle east respiratory syndrome coronavirus (mers-cov) shedding is important for infection control. the detection of mers-cov sub-genomic mrnas indicates that the virus is replicative. this study examined the duration for detecting mers-cov sub-genomic mrna compared with genomic rna in diverse respiratory specimens.201829753119
network analysis of mers coronavirus within households, communities, and hospitals to identify most centralized and super-spreading in the arabian peninsula, 2012 to 2016.contact history is crucial during an infectious disease outbreak and vital when seeking to understand and predict the spread of infectious diseases in human populations. the transmission connectivity networks of people infected with highly contagious middle east respiratory syndrome coronavirus (mers-cov) in saudi arabia were assessed to identify super-spreading events among the infected patients between 2012 and 2016. of the 1379 mers cases recorded during the study period, 321 (23.3%) cases we ...201829854034
an evaluation of emergency guidelines issued by the world health organization in response to four infectious disease outbreaks.the production of high-quality guidelines in response to public health emergencies poses challenges for the world health organization (who). the urgent need for guidance and the paucity of structured scientific data on emerging diseases hinder the formulation of evidence-informed recommendations using standard methods and procedures.201829847593
molecular dynamics of middle east respiratory syndrome coronavirus (mers cov) fusion heptad repeat trimers.structural studies related to middle east respiratory syndrome coronavirus (mers cov) infection process are so limited. in this study, molecular dynamics (md) simulations were carried out to unravel changes in the mers cov heptad repeat domains (hrs) and factors affecting fusion state hr stability. results indicated that hr trimer is more rapidly stabilized, having stable system energy and lower root mean square deviations (rmsds). while trimers were the predominant active form of covs hrs, mono ...201829803965
nucleocapsid protein-dependent assembly of the rna packaging signal of middle east respiratory syndrome coronavirus.middle east respiratory syndrome coronavirus (mers-cov) consists of a positive-sense, single-stranded rna genome and four structural proteins: the spike, envelope, membrane, and nucleocapsid protein. the assembly of the viral genome into virus particles involves viral structural proteins and is believed to be mediated through recognition of specific sequences and rna structures of the viral genome.201829793506
live-attenuated bivalent measles virus-derived vaccines targeting middle east respiratory syndrome coronavirus induce robust and multifunctional t cell responses against both viruses in an appropriate mouse model.cases of middle east respiratory syndrome coronavirus (mers-cov) continue to occur, making it one of the who´s targets for accelerated vaccine development. one vaccine candidate is based on live-attenuated measles virus (mv) vaccine encoding the mers-cov spike glycoprotein (mers-s). mvvac2-mers-s(h) induces robust humoral and cellular immunity against mers-s mediating protection. here, the induction and nature of immunity after vaccination with mvvac2-mers-s(h) or novel mvvac2-mers-n were furthe ...201829902727
a rapid and specific assay for the detection of mers-cov.middle east respiratory syndrome coronavirus (mers-cov) is a novel human coronavirus that can cause human respiratory disease. the development of a detection method for this virus that can lead to rapid and accurate diagnosis would be significant. in this study, we established a nucleic acid visualization technique that combines the reverse transcription loop-mediated isothermal amplification technique and a vertical flow visualization strip (rt-lamp-vf) to detect the n gene of mers-cov. the rt- ...201829896174
middle east respiratory syndrome coronavirus and bat coronavirus hku9 both can utilize grp78 for attachment onto host cells.coronavirus tropism is predominantly determined by the interaction between coronavirus spikes and the host receptors. in this regard, coronaviruses have evolved a complicated receptor-recognition system through their spike proteins. spikes from highly related coronaviruses can recognize distinct receptors, whereas spikes of distant coronaviruses can employ the same cell-surface molecule for entry. moreover, coronavirus spikes can recognize a broad range of cell-surface molecules in addition to t ...201829887526
underlying trend, seasonality, prediction, forecasting and the contribution of risk factors: an analysis of globally reported cases of middle east respiratory syndrome coronavirus.this study set out to identify and analyse trends and seasonal variations of monthly global reported cases of the middle east respiratory syndrome coronavirus (mers-cov). it also made a prediction based on the reported and extrapolated into the future by forecasting the trend. finally, the study assessed contributions of various risk factors in the reported cases. the motivation for this study is that mers-cov remains among the list of blueprint priority and potential pandemic diseases globally. ...201829886854
chaperna-mediated assembly of ferritin-based middle east respiratory syndrome-coronavirus nanoparticles.the folding of monomeric antigens and their subsequent assembly into higher ordered structures are crucial for robust and effective production of nanoparticle (np) vaccines in a timely and reproducible manner. despite significant advances in in silico design and structure-based assembly, most engineered nps are refractory to soluble expression and fail to assemble as designed, presenting major challenges in the manufacturing process. the failure is due to a lack of understanding of the kinetic p ...201829868035
global seasonal occurrence of middle east respiratory syndrome coronavirus (mers-cov) infection.middle east respiratory syndrome coronavirus (mers-cov) is an evolving global health crisis. despite recent efforts, there are numerous notable gaps in the understanding of mers-cov seasonal diversity. we aimed at investigating the global seasonal occurrence of middle east respiratory syndrome coronavirus (mers-cov) outbreaks.201829949167
underlying trend, seasonality, prediction, forecasting and the contribution of risk factors: an analysis of globally reported cases of middle east respiratory syndrome coronavirus - corrigendum. 201829945686
challenges of convalescent plasma infusion therapy in middle east respiratory coronavirus infection: a single centre experience.the effects of convalescent plasma (cp) infusion, one of the treatment options for severe middle east respiratory syndrome coronavirus (mers-cov) infections, have not yet been evaluated.201829923831
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
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
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
a human dpp4-knockin mouse's susceptibility to infection by authentic and pseudotyped mers-cov.infection by the middle east respiratory syndrome coronavirus (mers-cov) causes respiratory illness and has a high mortality rate (~35%). the requirement for the virus to be manipulated in a biosafety level three (bsl-3) facility has impeded development of urgently-needed antiviral agents. here, we established anovel mouse model by inserting human dipeptidyl peptidase 4 (hdpp4) into the rosa26 locus using crispr/cas9, resulting in global expression of the transgene in a genetically stable mouse ...201830142928
naadp-dependent ca2+ signaling regulates middle east respiratory syndrome-coronavirus pseudovirus translocation through the endolysosomal system.middle east respiratory syndrome coronavirus (mers-cov) infections are associated with a significant mortality rate, and existing drugs show poor efficacy. identifying novel targets/pathways required for mers infectivity is therefore important for developing novel therapeutics. as an enveloped virus, translocation through the endolysosomal system provides one pathway for cellular entry of mers-cov. in this context, ca2+-permeable channels within the endolysosomal system regulate both the luminal ...201830121440
the endonucleolytic rna cleavage function of nsp1 of middle east respiratory syndrome coronavirus promotes the production of infectious virus particles in specific human cell lines.middle east respiratory syndrome coronavirus (mers-cov) nsp1 suppresses host gene expression in expressed cells by inhibiting translation and inducing endonucleolytic cleavage of host mrnas, the latter of which leads to mrna decay. we examined the biological functions of nsp1 in infected cells and its role in virus replication by using wild-type mers-cov and two mutant viruses with specific mutations in the nsp1; one mutant lacked both biological functions, while the other lacked the rna cleavag ...201830111568
mortality rate of icu patients with the middle east respiratory syndrome - coronavirus infection at king fahad hospital, jeddah, saudi arabia.the middle east respiratory syndrome coronavirus (mers-cov) is a novel coronavirus circulating in the arabian peninsula since september 2012. it leads to significant respiratory disease and among patients with co-morbidities is associated with high mortality. this research studied the mortality rate of mers-cov among intensive care unit (icu) patients and the correlation of mortality with different co-morbidities.201830102495
human β-defensin 2 plays a regulatory role in innate antiviral immunity and is capable of potentiating the induction of antigen-specific immunity.antimicrobial peptides (amps) are primarily known for their innate immune defense against invading microorganisms, including viruses. in addition, recent research has suggested their modulatory activity in immune induction. given that most subunit vaccines require an adjuvant to achieve effective immune induction through the activation of innate immunity, amps are plausible candidate molecules for stimulating not only innate immune but also adaptive immune responses.201830089512
middle east respiratory syndrome coronavirus (mers-cov) infection: epidemiology, pathogenesis and clinical characteristics.middle east respiratory syndrome coronavirus-(mers-cov) infection is an evolving worldwide health crisis. the early diagnosis and management of the disease remains a major challenge. this study designed to discuss the epidemiology, pathogenesis and clinical appearances of mers-cov infections.201830070331
inhibition of stress granule formation by middle east respiratory syndrome coronavirus 4a accessory protein facilitates viral translation, leading to efficient virus replication.stress granule (sg) formation is generally triggered as a result of stress-induced translation arrest. the impact of sg formation on virus replication varies among different viruses, and the significance of sgs in coronavirus (cov) replication is largely unknown. the present study examined the biological role of sgs in middle east respiratory syndrome (mers)-cov replication. the mers-cov 4a accessory protein is known to inhibit sg formation in cells in which it was expressed by binding to double ...201830068649
middle east respiratory syndrome coronavirus spike protein is not activated directly by cellular furin during viral entry into target cells.middle east respiratory syndrome coronavirus (mers-cov) utilizes host cellular proteases to enter cells. a previous report shows that furin, which is distributed mainly in the golgi apparatus and cycled to the cell surface and endosomes, proteolytically activates the mers-cov spike (s) protein following receptor binding to mediate fusion between the viral and cellular membranes. in this study, we reexamined furin usage by mers-cov using a real-time pcr-based virus cell entry assay after inhibiti ...201830021905
proficiency testing for the detection of middle east respiratory syndrome coronavirus demonstrates global capacity to detect middle east respiratory syndrome coronavirus.the first reported case of middle east respiratory syndrome coronavirus (mers-cov) infection was identified in saudi arabia in september 2012, since which time there have been over 2000 laboratory-confirmed cases, including 750 deaths in 27 countries. nucleic acid testing (nat) is the preferred method for the detection of mers-cov. a single round of a proficiency testing program (ptp) was used to assess the capability of laboratories globally to accurately detect the presence of mers-cov using n ...201830016543
clinical management of respiratory syndrome in patients hospitalized for suspected middle east respiratory syndrome coronavirus infection in the paris area from 2013 to 2016.patients with suspected middle east respiratory syndrome coronavirus (mers-cov) infection should be hospitalized in isolation wards to avoid transmission. this suspicion can also lead to medical confusion and inappropriate management of acute respiratory syndrome due to causes other than mers-cov.201830012113
structural definition of a unique neutralization epitope on the receptor-binding domain of mers-cov spike glycoprotein.the major mechanism of antibody-mediated neutralization of the middle east respiratory syndrome coronavirus (mers-cov) involves competition with the cellular receptor dipeptidyl peptidase 4 (dpp4) for binding to the receptor-binding domain (rbd) of the spike (s) glycoprotein. here, we report a unique epitope and unusual neutralizing mechanism of the isolated human antibody mers-4. structurally, mers-4 approached the rbd from the outside of the rbd-dpp4 binding interface. such binding resulted in ...201829996104
tmprss11a activates the influenza a virus hemagglutinin and the mers coronavirus spike protein and is insensitive against blockade by hai-1.the influenza virus hemagglutinin (ha) facilitates viral entry into target cells. cleavage of ha by host cell proteases is essential for viral infectivity, and the responsible enzymes are potential targets for antiviral intervention. the type ii transmembrane serine protease (ttsp) tmprss2 has been identified as an ha activator in cell culture and in the infected host. however, it is less clear whether tmprss2-related enzymes can also activate ha for spread in target cells. moreover, the activit ...201829976755
enhanced protection in mice induced by immunization with inactivated whole viruses compare to spike protein of middle east respiratory syndrome coronavirus.the persistent public health threat of infection with middle east respiratory syndrome coronavirus (mers-cov) highlights the need for an effective and safe mers-cov vaccine. in this study, we prepared and vaccinated mice with either a spike (s) protein or inactivated whole mers-cov (iv) with a combined adjuvant (alum+cpg) as a vaccine formulation. similar levels of the anti-s protein igg response and neutralizing activity were induced by both the s protein and iv vaccines. in addition, immune re ...201829618723
reduction of soluble dipeptidyl peptidase 4 levels in plasma of patients infected with middle east respiratory syndrome coronavirus.dipeptidyl peptidase 4 (dpp4) is a receptor for mers-cov. the soluble form of dpp4 (sdpp4) circulates systematically and can competitively inhibit mers-cov entry into host cells. here, we measured the concentration of sdpp4 in the plasma and sputa of 14 mers-cov-infected patients of various degrees of disease severity. the concentration of sdpp4 in the plasma of mers patients (474.76 ± 108.06 ng/ml) was significantly lower than those of healthy controls (703.42 ± 169.96 ng/ml), but there were no ...201829587190
early identification of pneumonia patients at increased risk of middle east respiratory syndrome coronavirus infection in saudi arabia.the rapid and accurate identification of individuals who are at high risk of middle east respiratory syndrome coronavirus (mers-cov) infection remains a major challenge for the medical and scientific communities. the aim of this study was to develop and validate a risk prediction model for the screening of suspected cases of mers-cov infection in patients who have developed pneumonia.201829550445
structure-guided design of potent and permeable inhibitors of mers coronavirus 3cl protease that utilize a piperidine moiety as a novel design element.there are currently no approved vaccines or small molecule therapeutics available for the prophylaxis or treatment of middle east respiratory syndrome coronavirus (mers-cov) infections. mers-cov 3cl protease is essential for viral replication; consequently, it is an attractive target that provides a potentially effective means of developing small molecule therapeutics for combatting mers-cov. we describe herein the structure-guided design and evaluation of a novel class of inhibitors of mers-cov ...201829544147
the use of complementary and alternative medicine by patients with cancer: a cross-sectional survey in saudi arabia.a significant proportion of cancer patients use complementary and alternative medicine (cam) along with conventional therapies (ct), whereas a smaller proportion delay or defer ct in favor of cam. previous studies exploring cam use among cancer patients in the middle east region have shown discrepant results. this study investigates the prevalence and pattern of cam use by saudi cancer patients. it also discusses the possible benefits and harm related to cam use by cancer patients, and it explor ...201829530034
middle east respiratory syndrome: what we learned from the 2015 outbreak in the republic of korea.middle east respiratory syndrome coronavirus (mers-cov) was first isolated from a patient with severe pneumonia in 2012. the 2015 korea outbreak of merscov involved 186 cases, including 38 fatalities. a total of 83% of transmission events were due to five superspreaders, and 44% of the 186 mers cases were the patients who had been exposed in nosocomial transmission at 16 hospitals. the epidemic lasted for 2 months and the government quarantined 16,993 individuals for 14 days to control the outbr ...201829506344
nurses' experiences of care for patients with middle east respiratory syndrome-coronavirus in south korea.this study aimed to identify nurses' experiences of care for patients with middle east respiratory syndrome-coronavirus (mers-cov). their experiences can be useful to establish a safer healthcare system in preparation for infectious disease outbreaks.201829502886
inactivation of ebola virus and middle east respiratory syndrome coronavirus in platelet concentrates and plasma by ultraviolet c light and methylene blue plus visible light, respectively.ebola virus (ebov) and middle east respiratory syndrome coronavirus (mers-cov) have been identified as potential threats to blood safety. this study investigated the efficacy of the theraflex uv-platelets and theraflex mb-plasma pathogen inactivation systems to inactivate ebov and mers-cov in platelet concentrates (pcs) and plasma, respectively.201829732571
lectin affinity plasmapheresis for middle east respiratory syndrome-coronavirus and marburg virus glycoprotein elimination.middle east respiratory syndrome coronavirus (mers-cov) and marburg virus (marv) are among the world health organization's top 8 emerging pathogens. both zoonoses share nonspecific early symptoms, a high lethality rate, and a reduced number of specific treatment options. therefore, we evaluated extracorporeal virus and glycoprotein (gp) elimination by lectin affinity plasmapheresis (lap).201829698959
blockade of the c5a-c5ar axis alleviates lung damage in hdpp4-transgenic mice infected with mers-cov.the pathogenesis of highly pathogenic middle east respiratory syndrome coronavirus (mers-cov) remains poorly understood. in a previous study, we established an hdpp4-transgenic (hdpp4-tg) mouse model in which mers-cov infection causes severe acute respiratory failure and high mortality accompanied by an elevated secretion of cytokines and chemokines. since excessive complement activation is an important factor that contributes to acute lung injury after viral infection, in this study, we investi ...201829691378
epidemiological factors and worldwide pattern of middle east respiratory syndrome coronavirus from 2013 to 2016.middle east respiratory syndrome coronavirus (mers-cov) is an emerging threat to global health security with high intensity and lethality. this study was conducted to investigate epidemiological factors and patterns related to this disease.201829670390
unusual presentation of middle east respiratory syndrome coronavirus leading to a large outbreak in riyadh during 2017.the hallmark of middle east respiratory syndrome coronavirus (mers-cov) disease is the ability to cause major health care-associated nosocomial outbreaks with superspreading events leading to massive numbers of cases and excessive morbidity and mortality. in this report, we describe a patient who presented with acute renal failure requiring hemodialysis and became a mers-cov superspreader, igniting a recent multihospital outbreak in riyadh.201829661625
asymptomatic middle east respiratory syndrome coronavirus infection using a serologic survey in korea.the rates of asymptomatic infection with middle east respiratory syndrome (mers) coronavirus vary. a serologic study was conducted to determine the asymptomatic mers infection rate in healthcare workers and non-healthcare workers by exposure status.201829656631
development of a risk-prediction model for middle east respiratory syndrome coronavirus infection in dialysis patients.introduction the middle east respiratory syndrome coronavirus (mers-cov) infection can cause transmission clusters and high mortality in hemodialysis facilities. we attempted to develop a risk-prediction model to assess the early risk of mers-cov infection in dialysis patients. methods this two-center retrospective cohort study included 104 dialysis patients who were suspected of mers-cov infection and diagnosed with rrt-pcr between september 2012 and june 2016 at king fahd general hospital in j ...201829656480
healthcare worker exposure to middle east respiratory syndrome coronavirus (mers-cov): revision of screening strategies urgently needed.middle east respiratory syndrome coronavirus (mers-cov) continues to cause frequent hospital outbreaks in saudi arabia, with emergency departments as the initial site of the spread of this virus.201829649550
factors associated with recovery delay in a sample of patients diagnosed by mers-cov rrt-pcr: a saudi arabian multicenter retrospective study.research evidence exists that poor prognosis is common in middle east respiratory syndrome coronavirus (mers-cov) patients.201829624866
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
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
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
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
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
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
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
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
a spike-modified middle east respiratory syndrome coronavirus (mers-cov) infectious clone elicits mild respiratory disease in infected rhesus macaques.the recurrence of new human cases of middle east respiratory syndrome coronavirus (mers-cov) underscores the need for effective therapeutic countermeasures. nonhuman primate models are considered the gold standard for preclinical evaluation of therapeutic countermeasures. however, mers-cov-induced severe respiratory disease in humans is associated with high viral loads in the lower respiratory tract, which may be difficult to achieve in nonhuman primate models. considering this limitation, we wa ...201830013082
genetic evidence of middle east respiratory syndrome coronavirus (mers-cov) and widespread seroprevalence among camels in kenya.we describe the first genome isolation of middle east respiratory syndrome coronavirus (mers-cov) in kenya. this fatal zoonotic pathogen was first described in the kingdom of saudi arabia in 2012. epidemiological and molecular evidence revealed zoonotic transmission from camels to humans and between humans. currently, mers-cov is classified by the who as having high pandemic potential requiring greater surveillance. previous studies of mers-cov in kenya mainly focused on site-specific and archiv ...201830570714
cd8+ t cells responding to the middle east respiratory syndrome coronavirus nucleocapsid protein delivered by vaccinia virus mva in mice.middle east respiratory syndrome coronavirus (mers-cov), a novel infectious agent causing severe respiratory disease and death in humans, was first described in 2012. antibodies directed against the mers-cov spike (s) protein are thought to play a major role in controlling mers-cov infection and in mediating vaccine-induced protective immunity. in contrast, relatively little is known about the role of t cell responses and the antigenic targets of mers-cov that are recognized by cd8+ t cells. in ...201830558354
the human sodium iodide symporter as a reporter gene for studying middle east respiratory syndrome coronavirus pathogenesis.single photon emission computed tomography (spect) is frequently used in oncology and cardiology to evaluate disease progression and/or treatment efficacy. such technology allows for real-time evaluation of disease progression and when applied to studying infectious diseases may provide insight into pathogenesis. insertion of a spect-compatible reporter gene into a virus may provide insight into mechanisms of pathogenesis and viral tropism. the human sodium iodide symporter (hnis), a spect and p ...201830541777
countrywide survey for mers-coronavirus antibodies in dromedaries and humans in pakistan.middle east respiratory syndrome coronavirus (mers-cov) is a zoonotic pathogen capable of causing severe respiratory disease in humans. although dromedary camels are considered as a major reservoir host, the mers-cov infection dynamics in camels are not fully understood. through surveillance in pakistan, nasal (n = 776) and serum (n = 1050) samples were collected from camels between november 2015 and february 2018. samples were collected from animal markets, free-roaming herds and abattoirs. an ...201830311100
overexpression of the nucleocapsid protein of middle east respiratory syndrome coronavirus up-regulates cxcl10.middle east respiratory syndrome coronavirus (mers-cov) causes respiratory diseases in humans and has a high mortality rate. during infection, mers-cov regulates several host cellular processes including antiviral response genes. in order to determine if the nucleocapsid protein of mers-cov (mers-n) plays a role in viral-host interactions, a murine monoclonal antibody was generated so as to allow detection of the protein in infected cells as well as in overexpression system. then, mers-n was sta ...201830242057
the battle against sars and mers coronaviruses: reservoirs and animal models.in humans, infection with the coronavirus, especially the severe acute respiratory syndrome coronavirus (sars-cov) and the emerging middle east respiratory syndrome coronavirus (mers-cov), induces acute respiratory failure, resulting in high mortality. irregular coronavirus related epidemics indicate that the evolutionary origins of these two pathogens need to be identified urgently and there are still questions related to suitable laboratory animal models. thus, in this review we aim to highlig ...201830891557
a novel nanobody targeting middle east respiratory syndrome coronavirus (mers-cov) receptor-binding domain has potent cross-neutralizing activity and protective efficacy against mers-cov.the newly emerged middle east respiratory syndrome coronavirus (mers-cov) continues to infect humans and camels, calling for efficient, cost-effective, and broad-spectrum strategies to control its spread. nanobodies (nbs) are single-domain antibodies derived from camelids and sharks and are potentially cost-effective antivirals with small size and great expression yield. in this study, we developed a novel neutralizing nb (nbms10) and its human-fc-fused version (nbms10-fc), both of which target ...201829950421
ultrapotent human neutralizing antibody repertoires against middle east respiratory syndrome coronavirus from a recovered patient.the middle east respiratory syndrome coronavirus (mers-cov) causes severe respiratory infection with a high (~35%) mortality rate. neutralizing antibodies targeting the spike of mers-cov have been shown to be a therapeutic option for treatment of lethal disease.201829846635
modeling the spread of middle east respiratory syndrome coronavirus in saudi arabia.middle east respiratory syndrome coronavirus has been persistent in the middle east region since 2012. abundant scientific evidence showed that dromedary camels are the primary host of the virus. majority of human cases (i.e., 75% or 88%) are due to human-to-human transmission, while the others are due to camel-to-human transmission. mathematical modeling of middle east respiratory syndrome coronavirus camel-to-camel transmission was lacking. using the plug-and-play likelihood-based inference fr ...201829846148
no molecular evidence of mers-cov circulation in jeddah, saudi arabia between 2010-2012: a single-center retrospective study.middle east respiratory syndrome coronavirus (mers-cov) is an emerging zoonotic viral pathogen and a serious public health concern. the virus was first reported in saudi arabia in 2012 and continues to be endemic in the region. most of the initial mers-cov cases in 2012 and early 2013 were sporadic, and it remains unclear whether mers-cov was circulating before 2012 or not. therefore, we tried here to find any molecular evidence of mers-cov circulation in humans before or during 2012 in the city ...201831865304
saracatinib inhibits middle east respiratory syndrome-coronavirus replication in vitro.the middle east respiratory syndrome-coronavirus (mers-cov), first identified in saudi arabia, is an emerging zoonotic pathogen that causes severe acute respiratory illness in humans with a high fatality rate. since its emergence, mers-cov continues to spread to countries outside of the arabian peninsula and gives rise to sporadic human infections following the entry of infected individuals to other countries, which can precipitate outbreaks similar to the one that occurred in south korea in 201 ...201829795047
effect of interferon alpha and cyclosporine treatment separately and in combination on middle east respiratory syndrome coronavirus (mers-cov) replication in a human in-vitro and ex-vivo culture model.middle east respiratory syndrome coronavirus (mers-cov) has emerged as a coronavirus infection of humans in the past 5 years. though confined to certain geographical regions of the world, infection has been associated with a case fatality rate of 35%, and this mortality may be higher in ventilated patients. as there are few readily available animal models that accurately mimic human disease, it has been a challenge to ethically determine what optimum treatment strategies can be used for this dis ...201829772254
heterologous prime-boost vaccination with adenoviral vector and protein nanoparticles induces both th1 and th2 responses against middle east respiratory syndrome coronavirus.the middle east respiratory syndrome coronavirus (mers-cov) is a highly pathogenic and zoonotic virus with a fatality rate in humans of over 35%. although several vaccine candidates have been developed, there is still no clinically available vaccine for mers-cov. in this study, we developed two types of mers-cov vaccines: a recombinant adenovirus serotype 5 encoding the mers-cov spike gene (ad5/mers) and spike protein nanoparticles formulated with aluminum (alum) adjuvant. next, we tested a hete ...201829739720
discovery of novel bat coronaviruses in south china that use the same receptor as middle east respiratory syndrome coronavirus.middle east respiratory syndrome coronavirus (mers-cov) has represented a human health threat since 2012. although several mers-related covs that belong to the same species as mers-cov have been identified from bats, they do not use the mers-cov receptor, dipeptidyl peptidase 4 (dpp4). here, we screened 1,059 bat samples from at least 30 bat species collected in different regions in south china and identified 89 strains of lineage c betacoronaviruses, including tylonycteris pachypus coronavirus ...201829669833
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