Publications

TitleAbstractYear
Filter
PMID(sorted ascending)
Filter
mers-coronavirus replication induces severe in vitro cytopathology and is strongly inhibited by cyclosporin a or interferon-α treatment.coronavirus (cov) infections are commonly associated with respiratory and enteric disease in humans and animals. the 2003 outbreak of severe acute respiratory syndrome (sars) highlighted the potentially lethal consequences of cov-induced disease in humans. in 2012, a novel cov (middle east respiratory syndrome coronavirus; mers-cov) emerged, causing 49 human cases thus far, of which 23 had a fatal outcome. in this study, we characterized mers-cov replication and cytotoxicity in human and monkey ...201323620378
update: severe respiratory illness associated with middle east respiratory syndrome coronavirus (mers-cov)--worldwide, 2012-2013.cdc continues to work in consultation with the world health organization (who) and other partners to better understand the public health risk posed by the middle east respiratory syndrome coronavirus (mers-cov), formerly known as novel coronavirus, which was first reported to cause human infection in september 2012. the continued reporting of new cases indicates that there is an ongoing risk for transmission to humans in the area of the arabian peninsula. new reports of cases outside the region ...201323760190
molecular basis of binding between novel human coronavirus mers-cov and its receptor cd26.the newly emergent middle east respiratory syndrome coronavirus (mers-cov) can cause severe pulmonary disease in humans, representing the second example of a highly pathogenic coronavirus, the first being sars-cov. cd26 (also known as dipeptidyl peptidase 4, dpp4) was recently identified as the cellular receptor for mers-cov. the engagement of the mers-cov spike protein with cd26 mediates viral attachment to host cells and virus-cell fusion, thereby initiating infection. here we delineate the mo ...201323831647
the emerging novel middle east respiratory syndrome coronavirus: the "knowns" and "unknowns".a novel lineage c betacoronavirus, originally named human coronavirus emc/2012 (hcov-emc) and recently renamed middle east respiratory syndrome coronavirus (mers-cov), that is phylogenetically closely related to tylonycteris bat coronavirus hku4 and pipistrellus bat coronavirus hku5, which we discovered in 2007 from bats in hong kong, has recently emerged in the middle east to cause a severe acute respiratory syndrome (sars)-like infection in humans. the first laboratory-confirmed case, which in ...201323883791
crystal structure of the receptor-binding domain from newly emerged middle east respiratory syndrome coronavirus.the newly emerged middle east respiratory syndrome coronavirus (mers-cov) has infected at least 77 people, with a fatality rate of more than 50%. alarmingly, the virus demonstrates the capability of human-to-human transmission, raising the possibility of global spread and endangering world health and economy. here we have identified the receptor-binding domain (rbd) from the mers-cov spike protein and determined its crystal structure. this study also presents a structural comparison of mers-cov ...201323903833
spiking the mers-coronavirus receptor.a novel coronavirus, the middle east respiratory syndrome coronavirus, recently emerged through zoonotic transmission, causing a severe lower respiratory tract infection in humans. in two recent papers, one published in cell research, the crystal structure of the viral receptor-binding domain in complex with the host cd26/dipeptidyl peptidase 4 receptor has now been characterized.201323938293
from sars coronavirus to novel animal and human coronaviruses.in 2003, severe acute respiratory syndrome coronavirus (sars-cov) caused one of the most devastating epidemics known to the developed world. there were two important lessons from this epidemic. firstly, coronaviruses, in addition to influenza viruses, can cause severe and rapidly spreading human infections. secondly, bats can serve as the origin and natural animal reservoir of deadly human viruses. since then, researchers around the world, especially those in asia where sars-cov was first identi ...201323977429
tracing the sars-coronavirus.four coronaviruses (hcov-229e, hcov-oc43, hcov-nl63, hcov-hku1) are endemic in humans and mainly associated with mild respiratory illnesses; whereas the other two coronaviruses [severe acute respiratory syndrome coronavirus (sars-cov) and middle east respiratory syndrome coronavirus (mers-cov)] present as emerging infections causing severe respiratory syndrome. coronaviruses evolve by accumulation of point mutations and recombination of genomes among different strains or species. mammalian coron ...201323977431
middle east respiratory syndrome coronavirus spike protein delivered by modified vaccinia virus ankara efficiently induces virus-neutralizing antibodies.middle east respiratory syndrome coronavirus (mers-cov) has recently emerged as a causative agent of severe respiratory disease in humans. here, we constructed recombinant modified vaccinia virus ankara (mva) expressing full-length mers-cov spike (s) protein (mva-mers-s). the genetic stability and growth characteristics of mva-mers-s make it a suitable candidate vaccine for clinical testing. vaccinated mice produced high levels of serum antibodies neutralizing mers-cov. thus, mva-mers-s may serv ...201323986586
engineering a replication-competent, propagation-defective middle east respiratory syndrome coronavirus as a vaccine candidate.middle east respiratory syndrome coronavirus (mers-cov) is an emerging coronavirus infecting humans that is associated with acute pneumonia, occasional renal failure, and a high mortality rate and is considered a threat to public health. the construction of a full-length infectious cdna clone of the mers-cov genome in a bacterial artificial chromosome is reported here, providing a reverse genetics system to study the molecular biology of the virus and to develop attenuated viruses as vaccine can ...201324023385
middle east respiratory syndrome coronavirus (mers-cov) causes transient lower respiratory tract infection in rhesus macaques.in 2012, a novel betacoronavirus, designated middle east respiratory syndrome coronavirus or mers-cov and associated with severe respiratory disease in humans, emerged in the arabian peninsula. to date, 108 human cases have been reported, including cases of human-to-human transmission. the availability of an animal disease model is essential for understanding pathogenesis and developing effective countermeasures. upon a combination of intratracheal, ocular, oral, and intranasal inoculation with ...201324062443
origin, evolution, and genotyping of emergent porcine epidemic diarrhea virus strains in the united states.coronaviruses are known to infect humans and other animals and cause respiratory and gastrointestinal diseases. here we report the emergence of porcine epidemic diarrhea virus (pedv) in the united states and determination of its origin, evolution, and genotypes based on temporal and geographical evidence. histological lesions in small intestine sections of affected pigs and the complete genomic sequences of three emergent strains of pedv isolated from outbreaks in minnesota and iowa were charact ...201324129257
isolation and characterization of a bat sars-like coronavirus that uses the ace2 receptor.the 2002-3 pandemic caused by severe acute respiratory syndrome coronavirus (sars-cov) was one of the most significant public health events in recent history. an ongoing outbreak of middle east respiratory syndrome coronavirus suggests that this group of viruses remains a key threat and that their distribution is wider than previously recognized. although bats have been suggested to be the natural reservoirs of both viruses, attempts to isolate the progenitor virus of sars-cov from bats have bee ...201324172901
a decade after sars: strategies for controlling emerging coronaviruses.two novel coronaviruses have emerged in humans in the twenty-first century: severe acute respiratory syndrome coronavirus (sars-cov) and middle east respiratory syndrome coronavirus (mers-cov), both of which cause acute respiratory distress syndrome (ards) and are associated with high mortality rates. there are no clinically approved vaccines or antiviral drugs available for either of these infections; thus, the development of effective therapeutic and preventive strategies that can be readily a ...201324217413
state of knowledge and data gaps of middle east respiratory syndrome coronavirus (mers-cov) in humans.between september 2012 and 22 october 2013, 144 laboratory-confirmed and 17 probable mers-cov cases from nine countries were notified to who.201324270606
lack of mers coronavirus neutralizing antibodies in humans, eastern province, saudi arabia.we used a lentiviral vector bearing the viral spike protein to detect neutralizing antibodies against middle east respiratory syndrome coronavirus (mers-cov) in persons from the eastern province of saudi arabia. none of the 268 samples tested displayed neutralizing activity, which suggests that mers-cov infections in humans are infrequent in this province.201324274664
interferon-β and mycophenolic acid are potent inhibitors of middle east respiratory syndrome coronavirus in cell-based assays.the middle east respiratory syndrome coronavirus (mers-cov) presents a novel emerging threat to public health worldwide. several treatments for infected individuals have been suggested including ifn, ribavirin and passive immunotherapy with convalescent plasma. administration of ifn-α2b and ribavirin has improved outcomes of mers-cov infection in rhesus macaques when administered within 8 h post-challenge. however, detailed and systematic evidence on the activity of other clinically available dr ...201424323636
proteolytic processing, deubiquitinase and interferon antagonist activities of middle east respiratory syndrome coronavirus papain-like protease.the emerging middle east respiratory syndrome coronavirus (mers-cov) causes severe pulmonary disease in humans and represents the second example of a highly pathogenic coronavirus (cov) following severe acute respiratory syndrome coronavirus (sars-cov). genomic studies revealed that two viral proteases, papain-like protease (plpro) and 3c-like protease (3clpro), process the polyproteins encoded by the mers-cov genomic rna. we previously reported that sars-cov plpro acts as both deubiquitinase (d ...201424362959
reverse transcription recombinase polymerase amplification assay for the detection of middle east respiratory syndrome coronavirus.the emergence of middle east respiratory syndrome coronavirus (mers-cov) in the eastern mediterranean and imported cases to europe has alerted public health authorities. currently, detection of mers-cov in patient samples is done by real-time rt-pcr. samples collected from suspected cases are sent to highly-equipped centralized laboratories for screening. a rapid point-of-care test is needed to allow more widespread mobile detection of the virus directly from patient material. in this study, we ...201324459611
middle east respiratory syndrome coronavirus (mers-cov): evidence and speculations.in 2012, a novel human coronavirus emerged and was tentatively named "middle east respiratory syndrome coronavirus" (mers-cov). the high mortality rate of mers-cov focused attention on the ecology of the virus. it has been found that mers-cov belongs to the group c lineage of the genus betacoronavirus. coronavirus surveillance studies in different populations of bats have suggested that they are probable reservoirs for this novel virus, and phylogenetic analysis of both the spike (s1) and rna-de ...201424515532
distinct immune response in two mers-cov-infected patients: can we go from bench to bedside?one year after the occurrence of the first case of infection by the middle east respiratory syndrome coronavirus (mers-cov) there is no clear consensus on the best treatment to propose. the world health organization, as well as several other national agencies, are still working on different clinical approaches to implement the most relevant treatment in mers-cov infection. we compared innate and adaptive immune responses of two patients infected with mers-cov to understand the underlying mechani ...201424551142
receptor variation and susceptibility to middle east respiratory syndrome coronavirus infection.the middle east respiratory syndrome coronavirus (mers-cov) recently spread from an animal reservoir to infect humans, causing sporadic severe and frequently fatal respiratory disease. appropriate public health and control measures will require discovery of the zoonotic mers coronavirus reservoirs. the relevant animal hosts are liable to be those that offer optimal mers virus cell entry. cell entry begins with virus spike (s) protein binding to dpp4 receptors. we constructed chimeric dpp4 recept ...201424554656
middle east respiratory syndrome coronavirus infection in dromedary camels in saudi arabia.the middle east respiratory syndrome (mers) is proposed to be a zoonotic disease; however, the reservoir and mechanism for transmission of the causative agent, the mers coronavirus, are unknown. dromedary camels have been implicated through reports that some victims have been exposed to camels, camels in areas where the disease has emerged have antibodies to the virus, and viral sequences have been recovered from camels in association with outbreaks of the disease among humans. nonetheless, whet ...201424570370
rapid generation of a mouse model for middle east respiratory syndrome.in this era of continued emergence of zoonotic virus infections, the rapid development of rodent models represents a critical barrier to public health preparedness, including the testing of antivirus therapy and vaccines. the middle east respiratory syndrome coronavirus (mers-cov) was recently identified as the causative agent of a severe pneumonia. given the ability of coronavirus to rapidly adapt to new hosts, a major public health concern is that mers-cov will further adapt to replication in ...201424599590
antibodies against mers coronavirus in dromedary camels, united arab emirates, 2003 and 2013.middle east respiratory syndrome coronavirus (mers-cov) has caused an ongoing outbreak of severe acute respiratory tract infection in humans in the arabian peninsula since 2012. dromedary camels have been implicated as possible viral reservoirs. we used serologic assays to analyze 651 dromedary camel serum samples from the united arab emirates; 151 of 651 samples were obtained in 2003, well before onset of the current epidemic, and 500 serum samples were obtained in 2013. recombinant spike prote ...201424655412
novel betacoronavirus in dromedaries of the middle east, 2013.in 2013, a novel betacoronavirus was identified in fecal samples from dromedaries in dubai, united arab emirates. antibodies against the recombinant nucleocapsid protein of the virus, which we named dromedary camel coronavirus (dccov) uae-hku23, were detected in 52% of 59 dromedary serum samples tested. in an analysis of 3 complete dccov uae-hku23 genomes, we identified the virus as a betacoronavirus in lineage a1. the dccov uae-hku23 genome has g+c contents; a general preference for g/c in the ...201424655427
a conformation-dependent neutralizing monoclonal antibody specifically targeting receptor-binding domain in middle east respiratory syndrome coronavirus spike protein.prophylactic and therapeutic strategies are urgently needed to combat infections caused by the newly emerged middle east respiratory syndrome coronavirus (mers-cov). here, we have developed a neutralizing monoclonal antibody (mab), designated mersmab1, which potently blocks mers-cov entry into human cells. biochemical assays reveal that mersmab1 specifically binds to the receptor-binding domain (rbd) of the mers-cov spike protein and thereby competitively blocks the binding of the rbd to its cel ...201424719424
identification of human neutralizing antibodies against mers-cov and their role in virus adaptive evolution.the newly emerging middle east respiratory syndrome coronavirus (mers-cov) causes a severe acute respiratory syndrome-like disease with ∼43% mortality. given the recent detection of virus in dromedary camels, zoonotic transfer of mers-cov to humans is suspected. in addition, little is known about the role of human neutralizing ab (nab) pressure as a driving force in mers-cov adaptive evolution. here, we used a well-characterized nonimmune human ab-phage library and a panning strategy with proteo ...201424778221
potent neutralization of mers-cov by human neutralizing monoclonal antibodies to the viral spike glycoprotein.the recently identified middle east respiratory syndrome coronavirus (mers-cov) causes severe and fatal acute respiratory illness in humans. however, no prophylactic and therapeutic agents specifically against mers-cov are currently available. entry of mers-cov into target cells depends on binding of the receptor binding domain (rbd) of the viral envelope spike glycoprotein to the cellular receptor dipeptidyl peptidase 4 (dpp4). we report the isolation and characterization of two potent human rb ...201424778414
middle east respiratory syndrome coronavirus quasispecies that include homologues of human isolates revealed through whole-genome analysis and virus cultured from dromedary camels in saudi arabia.abstract complete middle east respiratory syndrome coronavirus (mers-cov) genome sequences were obtained from nasal swabs of dromedary camels sampled in the kingdom of saudi arabia through direct analysis of nucleic acid extracts or following virus isolation in cell culture. consensus dromedary mers-cov genome sequences were the same with either template source and identical to published human mers-cov sequences. however, in contrast to individual human cases, where only clonal genomic sequences ...201424781747
exceptionally potent neutralization of middle east respiratory syndrome coronavirus by human monoclonal antibodies.the recently discovered middle east respiratory syndrome coronavirus (mers-cov) continues to infect humans, with high mortality. specific, highly effective therapeutics and vaccines against the mers-cov are urgently needed to save human lives and address the pandemic concerns. we identified three human monoclonal antibodies (mabs), m336, m337, and m338, targeting the receptor (cd26/dpp4) binding domain (rbd) of the mers-cov spike glycoprotein from a very large naïve-antibody library (containing ...201424789777
screening of an fda-approved compound library identifies four small-molecule inhibitors of middle east respiratory syndrome coronavirus replication in cell culture.coronaviruses can cause respiratory and enteric disease in a wide variety of human and animal hosts. the 2003 outbreak of severe acute respiratory syndrome (sars) first demonstrated the potentially lethal consequences of zoonotic coronavirus infections in humans. in 2012, a similar previously unknown coronavirus emerged, middle east respiratory syndrome coronavirus (mers-cov), thus far causing over 650 laboratory-confirmed infections, with an unexplained steep rise in the number of cases being r ...201424841269
t cell-mediated immune response to respiratory coronaviruses.emerging respiratory coronaviruses such as the severe acute respiratory syndrome coronavirus (sars-cov) and middle east respiratory syndrome coronavirus (mers-cov) pose potential biological threats to humans. sars and mers are manifested as severe atypical pneumonia associated with high morbidity and mortality in humans. the majority of studies carried out in sars-cov-infected humans and animals attribute a dysregulated/exuberant innate response as a leading contributor to sars-cov-mediated path ...201424845462
host species restriction of middle east respiratory syndrome coronavirus through its receptor, dipeptidyl peptidase 4.middle east respiratory syndrome coronavirus (mers-cov) emerged in 2012. recently, the mers-cov receptor dipeptidyl peptidase 4 (dpp4) was identified and the specific interaction of the receptor-binding domain (rbd) of mers-cov spike protein and dpp4 was determined by crystallography. animal studies identified rhesus macaques but not hamsters, ferrets, or mice to be susceptible for mers-cov. here, we investigated the role of dpp4 in this observed species tropism. cell lines of human and nonhuman ...201424899185
unanswered questions about the middle east respiratory syndrome coronavirus (mers-cov).the middle east respiratory syndrome coronavirus (mers-cov) represents a current threat to the arabian peninsula, and potential pandemic disease. as of june 3, 2014, mers cov has reportedly infected 688 people and killed 282. we briefly summarize the state of the outbreak, and highlight unanswered questions and various explanations for the observed epidemiology.201424920393
antiviral drugs specific for coronaviruses in preclinical development.coronaviruses are positive stranded rna viruses that cause respiratory, enteric and central nervous system diseases in many species, including humans. until recently, the relatively low burden of disease in humans caused by few of these viruses impeded the development of coronavirus specific therapeutics. however, the emergence of severe acute respiratory syndrome coronavirus (sars-cov), and more recently, middle east respiratory syndrome coronavirus (mers-cov), has impelled the development of s ...201424997250
rooting the phylogenetic tree of middle east respiratory syndrome coronavirus by characterization of a conspecific virus from an african bat.the emerging middle east respiratory syndrome coronavirus (mers-cov) causes lethal respiratory infections mainly on the arabian peninsula. the evolutionary origins of mers-cov are unknown. we determined the full genome sequence of a cov directly from fecal material obtained from a south african neoromicia capensis bat (neocov). neocov shared essential details of genome architecture with mers-cov. eighty-five percent of the neocov genome was identical to mers-cov at the nucleotide level. based on ...201425031349
coronaviruses: severe acute respiratory syndrome coronavirus and middle east respiratory syndrome coronavirus in travelers.middle east respiratory syndrome coronavirus (mers-cov) is currently the focus of global attention. in this review, we describe virological, clinical, epidemiological features and interim travel advice and guidelines regarding mers-cov. we compare and contrast these with the severe acute respiratory syndrome coronavirus (sars-cov).201425033169
detection of the middle east respiratory syndrome coronavirus genome in an air sample originating from a camel barn owned by an infected patient.middle east respiratory syndrome coronavirus (mers-cov) is a novel betacoronavirus that has been circulating in the arabian peninsula since 2012 and causing severe respiratory infections in humans. while bats were suggested to be involved in human mers-cov infections, a direct link between bats and mers-cov is uncertain. on the other hand, serological and virological data suggest dromedary camels as the potential animal reservoirs of mers-cov. recently, we isolated mers-cov from a camel and its ...201425053787
geographic distribution of mers coronavirus among dromedary camels, africa.we found serologic evidence for the circulation of middle east respiratory syndrome coronavirus among dromedary camels in nigeria, tunisia, and ethiopia. circulation of the virus among dromedaries across broad areas of africa may indicate that this disease is currently underdiagnosed in humans outside the arabian peninsula.201425062254
receptor usage and cell entry of bat coronavirus hku4 provide insight into bat-to-human transmission of mers coronavirus.middle east respiratory syndrome coronavirus (mers-cov) currently spreads in humans and causes ∼ 36% fatality in infected patients. believed to have originated from bats, mers-cov is genetically related to bat coronaviruses hku4 and hku5. to understand how bat coronaviruses transmit to humans, we investigated the receptor usage and cell entry activity of the virus-surface spike proteins of hku4 and hku5. we found that dipeptidyl peptidase 4 (dpp4), the receptor for mers-cov, is also the receptor ...201425114257
infection with mers-cov causes lethal pneumonia in the common marmoset.the availability of a robust disease model is essential for the development of countermeasures for middle east respiratory syndrome coronavirus (mers-cov). while a rhesus macaque model of mers-cov has been established, the lack of uniform, severe disease in this model complicates the analysis of countermeasure studies. modeling of the interaction between the mers-cov spike glycoprotein and its receptor dipeptidyl peptidase 4 predicted comparable interaction energies in common marmosets and human ...201425144235
middle east respiratory syndrome coronavirus: transmission and phylogenetic evolution.the middle east respiratory syndrome coronavirus (mers-cov) was first described in 2012 and, subsequently, many cases were reported with a lower case fatality rate than initial cases. humans can become infected within their communities and transmission can then be amplified in the healthcare setting. contact investigation among cases shows a variable amount of spread among family members and healthcare workers. so far, circulating virus strains remain similar under continuous monitoring, with no ...201425178651
immunogenicity of an adenoviral-based middle east respiratory syndrome coronavirus vaccine in balb/c mice.a new type of coronavirus has been identified as the causative agent underlying middle east respiratory syndrome (mers). the mers coronavirus (mers-cov) has spread in the middle east, but cases originating in the middle east have also occurred in the european union and the usa. eight hundred and thirty-seven cases of mers-cov infection have been confirmed to date, including 291 deaths. mers-cov has infected dromedary camel populations in the middle east at high rates, representing an immediate s ...201425192975
searching for an ideal vaccine candidate among different mers coronavirus receptor-binding fragments--the importance of immunofocusing in subunit vaccine design.the newly emerged middle east respiratory syndrome coronavirus (mers-cov) is currently spreading among humans, making development of effective mers vaccines a high priority. a defined receptor-binding domain (rbd) in mers-cov spike protein can potentially serve as a subunit vaccine candidate against mers-cov infections. to identify an ideal vaccine candidate, we have constructed five different versions of rbd fragments, s350-588-fc, s358-588-fc, s367-588-fc, s367-606-fc, and s377-588-fc (their n ...201425240756
[dromedary camels and middle east respiratory syndrome: mers coronavirus in the 'ship of the desert'].middle east respiratory syndrome coronavirus (mers-cov) is a novel coronavirus, identified in patients with respiratory symptoms in the middle east. accumulating evidence points to dromedary camels as being reservoirs. mers-cov has been isolated from dromedaries, and dromedary mers-cov is nearly identical to human mers-cov. camel and human mers-cov genome sequences from the same geographic areas cluster together. both on the arabian peninsula and in africa high percentages of adult dromedaries a ...201425248734
ifitm proteins inhibit entry driven by the mers-coronavirus spike protein: evidence for cholesterol-independent mechanisms.the interferon-inducible transmembrane (ifitm) proteins 1, 2 and 3 inhibit the host cell entry of several enveloped viruses, potentially by promoting the accumulation of cholesterol in endosomal compartments. ifitm3 is essential for control of influenza virus infection in mice and humans. in contrast, the role of ifitm proteins in coronavirus infection is less well defined. employing a retroviral vector system for analysis of coronavirus entry, we investigated the susceptibility of human-adapted ...201425256397
host cell entry of middle east respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein.middle east respiratory syndrome coronavirus (mers-cov) is a newly identified betacoronavirus causing high morbidity and mortality in humans. the coronavirus spike (s) protein is the main determinant of viral entry, and although it was previously shown that mers-cov s can be activated by various proteases, the details of the mechanisms of proteolytic activation of fusion are still incompletely characterized. here, we have uncovered distinctive characteristics of mers-cov s. we identify, by bioin ...201425288733
pathogenesis of middle east respiratory syndrome coronavirus.human coronaviruses (covs) mostly cause a common cold that is mild and self-limiting. zoonotic transmission of covs such as the recently identified middle east respiratory syndrome (mers)-cov and severe acute respiratory syndrome (sars)-cov, on the other hand, may be associated with severe lower respiratory tract infection. this article reviews the clinical and pathological data available on mers and compares it to sars. most importantly, chest radiographs and imaging results of patients with me ...201525294366
detecting differential transmissibilities that affect the size of self-limited outbreaks.our ability to respond appropriately to infectious diseases is enhanced by identifying differences in the potential for transmitting infection between individuals. here, we identify epidemiological traits of self-limited infections (i.e. infections with an effective reproduction number satisfying [0 < r eff < 1) that correlate with transmissibility. our analysis is based on a branching process model that permits statistical comparison of both the strength and heterogeneity of transmission for tw ...201425356657
middle east respiratory syndrome coronavirus: epidemiology and disease control measures.the emergence of middle east respiratory syndrome coronavirus (mers-cov) infection in 2012 resulted in an increased concern of the spread of the infection globally. mers-cov infection had previously caused multiple health-care-associated outbreaks and resulted in transmission of the virus within families. community onset mers-cov cases continue to occur. dromedary camels are currently the most likely animal to be linked to human mers-cov cases. serologic tests showed significant infection in adu ...201425395865
bartonella dromedarii sp. nov. isolated from domesticated camels (camelus dromedarius) in israel.bartonella spp. are fastidious, gram-negative bacilli that cause a wide spectrum of diseases in humans. most bartonella spp. have adapted to a specific host, generally a domestic or wild mammal. dromedary camels (camelus dromedarius) have become a focus of growing public-health interest because they have been identified as a reservoir host for the middle east respiratory syndrome coronavirus. nevertheless, data on camel zoonoses are limited. we aimed to study the occurrence of bartonella bactere ...201425409267
replication and shedding of mers-cov in upper respiratory tract of inoculated dromedary camels.in 2012, a novel coronavirus associated with severe respiratory disease in humans emerged in the middle east. epidemiologic investigations identified dromedary camels as the likely source of zoonotic transmission of middle east respiratory syndrome coronavirus (mers-cov). here we provide experimental support for camels as a reservoir for mers-cov. we inoculated 3 adult camels with a human isolate of mers-cov and a transient, primarily upper respiratory tract infection developed in each of the 3 ...025418529
receptor-binding domain-based subunit vaccines against mers-cov.development of effective vaccines, in particular, subunit-based vaccines, against emerging middle east respiratory syndrome (mers) caused by the mers coronavirus (mers-cov) will provide the safest means of preventing the continuous spread of mers in humans and camels. this review briefly describes the structure of the mers-cov spike (s) protein and its receptor-binding domain (rbd), discusses the current status of mers vaccine development and illustrates the strategies used to develop rbd-based ...201525445336
host cell proteases: critical determinants of coronavirus tropism and pathogenesis.coronaviruses are a large group of enveloped, single-stranded positive-sense rna viruses that infect a wide range of avian and mammalian species, including humans. the emergence of deadly human coronaviruses, severe acute respiratory syndrome coronavirus (sars-cov), and middle east respiratory syndrome coronavirus (mers-cov) have bolstered research in these viral and often zoonotic pathogens. while coronavirus cell and tissue tropism, host range, and pathogenesis are initially controlled by inte ...201425445340
a screen of the nih clinical collection small molecule library identifies potential anti-coronavirus drugs.with the recent emergence of middle east respiratory syndrome coronavirus in humans and the outbreak of devastating porcine epidemic diarrhea coronavirus in swine, therapeutic intervention is urgently needed. however, anti-coronavirus drugs currently are not available. in an effort to assist rapid development of anti-coronavirus drugs, here we screened the nih clinical collection in cell culture using a luciferase reporter-expressing recombinant murine coronavirus. of the 727 compounds screened, ...201525451075
middle east respiratory syndrome coronavirus (mers-cov): prevention in travelers.middle east respiratory syndrome coronavirus (mers-cov), a novel coronavirus that causes a severe lower respiratory tract infection in humans, emerged in the middle east in 2012. since then, mers-cov has caused an ongoing epidemic in the arabian peninsula with sporadic cases imported in europe, north africa, southeast asia, and the united states of america. as of 28th may 2014, 636 laboratory-confirmed cases of infection with mers-cov have been reported to world health organization including 14 ...201625457301
human-dromedary camel interactions and the risk of acquiring zoonotic middle east respiratory syndrome coronavirus infection.middle east respiratory syndrome coronavirus (mers-cov) cases without documented contact with another human mers-cov case make up 61% (517/853) of all reported cases. these primary cases are of particular interest for understanding the source(s) and route(s) of transmission and for designing long-term disease control measures. dromedary camels are the only animal species for which there is convincing evidence that it is a host species for mers-cov and hence a potential source of human infections ...201625545147
study of viral pathogenesis in humanized mice.many of the viral pathogens that cause infectious diseases in humans have a highly restricted species tropism, making the study of their pathogenesis and the development of clinical therapies difficult. the improvement of humanized mouse models over the past 30 years has greatly facilitated researchers' abilities to study host responses to viral infections in a cost effective and ethical manner. from hiv to hepatotropic viruses to middle east respiratory syndrome coronavirus, humanized mice have ...201525618248
reliable typing of mers-cov variants with a small genome fragment.middle east respiratory syndrome coronavirus (mers-cov) is an emerging pathogen that causes lower respiratory tract infection in humans. camels are the likely animal source for zoonotic infection, although exact transmission modes remain to be determined. human-to-human transmission occurs sporadically. the wide geographic distribution of mers-cov among dromedary camels and ongoing transmissions to humans provides concern for the evolution of a mers-cov variant with efficient human-to-human tran ...201525728084
emerging respiratory tract viral infections.this article reviews the clinical and treatment aspects of avian influenza viruses and the middle east respiratory syndrome coronavirus (mers-cov).201525764021
hepatitis e: a disease of reemerging importance.hepatitis e virus (hev) is the most common cause of acute viral hepatitis worldwide. originally considered to be restricted to humans, it is now clear that hev and hev-like viruses have several animal reservoirs with complex ecology and genetic diversity, as exemplified by the recent discovery of hev in dromedaries, a previously underestimated reservoir of zoonotic viruses prior to the emergence of middle east respiratory syndrome coronavirus. zoonotic foodborne transmission from pigs and feral ...201525773541
middle east respiratory syndrome: knowledge to date.to provide a conceptual and clinical review of middle east respiratory syndrome.201525785521
lack of middle east respiratory syndrome coronavirus transmission from infected camels.to determine risk for middle east respiratory syndrome coronavirus transmission from camels to humans, we tested serum from 191 persons with various levels of exposure to an infected dromedary herd. we found no serologic evidence of human infection, suggesting that zoonotic transmission of this virus from dromedaries is rare.201525811546
influenza a and b viruses but not mers-cov in hajj pilgrims, austria, 2014. 201525811672
middle east respiratory syndrome coronavirus "mers-cov": current knowledge gaps.the middle east respiratory syndrome coronavirus (mers-cov) that causes a severe lower respiratory tract infection in humans is now considered a pandemic threat to the gulf region. since its discovery in 2012, mers-cov has reached 23 countries affecting about 1100 people, including a dozen children, and claiming over 400 lives. compared to sars (severe acute respiratory syndrome), mers-cov appears to kill more people (40% versus 10%), more quickly, and is especially more severe in those with pre ...201526002405
protective efficacy of recombinant modified vaccinia virus ankara delivering middle east respiratory syndrome coronavirus spike glycoprotein.middle east respiratory syndrome coronavirus (mers-cov) causes severe respiratory disease in humans. we tested a recombinant modified vaccinia virus ankara (mva) vaccine expressing full-length mers-cov spike (s) glycoprotein by immunizing balb/c mice with either intramuscular or subcutaneous regimens. in all cases, mva-mers-s induced mers-cov-specific cd8(+) t cells and virus-neutralizing antibodies. vaccinated mice were protected against mers-cov challenge infection after transduction with the ...201526018172
two mutations were critical for bat-to-human transmission of middle east respiratory syndrome coronavirus.to understand how middle east respiratory syndrome coronavirus (mers-cov) transmitted from bats to humans, we compared the virus surface spikes of mers-cov and a related bat coronavirus, hku4. although hku4 spike cannot mediate viral entry into human cells, two mutations enabled it to do so by allowing it to be activated by human proteases. these mutations are present in mers-cov spike, explaining why mers-cov infects human cells. these mutations therefore played critical roles in the bat-to-hum ...201526063432
animal models for sars and mers coronaviruses.the emergence of severe acute respiratory syndrome coronavirus (sars-cov) and middle east respiratory syndrome coronavirus (mers-cov), two strains of animal coronaviruses that crossed the species barrier to infect and cause severe respiratory infections in humans within the last 12 years, have taught us that coronaviruses represent a global threat that does not recognize international borders. we can expect to see other novel coronaviruses emerge in the future. an ideal animal model should refle ...201526184451
inactivation and safety testing of middle east respiratory syndrome coronavirus.middle east respiratory syndrome coronavirus (mers-cov) is a recently emerged virus that has caused a number of human infections and deaths, primarily in the middle east. the transmission of mers-cov to humans has been proposed to be as a result of contact with camels, but evidence of human-to-human transmission also exists. in order to work with mers-cov in a laboratory setting, the us centers for disease control and prevention (cdc) has determined that mers-cov should be handled at a biosafety ...201526190637
treatment with lopinavir/ritonavir or interferon-β1b improves outcome of mers-cov infection in a nonhuman primate model of common marmoset.middle east respiratory syndrome coronavirus (mers-cov) causes severe disease in human with an overall case-fatality rate of >35%. effective antivirals are crucial for improving the clinical outcome of mers. although a number of repurposed drugs, convalescent-phase plasma, antiviral peptides, and neutralizing antibodies exhibit anti-mers-cov activity in vitro, most are not readily available or have not been evaluated in nonhuman primates. we assessed 3 repurposed drugs with potent in vitro anti- ...201526198719
bat-to-human: spike features determining 'host jump' of coronaviruses sars-cov, mers-cov, and beyond.both severe acute respiratory syndrome coronavirus (sars-cov) and middle east respiratory syndrome coronavirus (mers-cov) are zoonotic pathogens that crossed the species barriers to infect humans. the mechanism of viral interspecies transmission is an important scientific question to be addressed. these coronaviruses contain a surface-located spike (s) protein that initiates infection by mediating receptor-recognition and membrane fusion and is therefore a key factor in host specificity. in addi ...201526206723
dromedary camels and the transmission of middle east respiratory syndrome coronavirus (mers-cov).middle east respiratory syndrome coronavirus (mers-cov) is an existential threat to global public health. the virus has been repeatedly detected in dromedary camels (camelus dromedarius). adult animals in many countries in the middle east as well as in north and east africa showed high (>90%) seroprevalence to the virus. middle east respiratory syndrome coronavirus isolated from dromedaries is genetically and phenotypically similar to viruses from humans. we summarize current understanding of th ...201726256102
middle-east respiratory syndrome coronavirus: is it worth a world panic?in 2012 middle-east respiratory syndrome coronavirus (mers-cov) was evolved in the arabian peninsula. tremendous and successful efforts have been conducted to discover the genome structure, epidemiology, clinical signs, pathogenesis, diagnosis and antiviral therapy. taphozous perforatus bats are the incriminated reservoir host and camels are the currently confirmed animal linker. the virus resulted in less than 1000 infected cases and 355 deaths. the case fatality rate of the mers-cov is high, h ...201526279980
structural basis for the neutralization of mers-cov by a human monoclonal antibody mers-27.the recently reported middle east respiratory syndrome coronavirus (mers-cov) causes severe respiratory illness in humans with an approximately 30% mortality rate. the envelope spike glycoprotein on the surface of mers-cov mediates receptor binding, membrane fusion, and viral entry. we previously reported two human monoclonal antibodies that target the receptor binding domain (rbd) of the spike and exhibit strong neutralization activity against live and pesudotyped mers-cov infection. here we de ...201526281793
[molecular diagnosis and phylogenetic analysis of the first mers case in turkey].coronaviruses (cov) are enveloped, spherical, single-stranded positive-sense rna viruses causing mainly respiratory and intestinal infections in animals and humans. until recently five types of human coronaviruses (hcov-oc43, hcov-hku1, hcov-nl63, hcov-229e, sars-cov) have been known, however a novel cov has been identified in 2012 in saudi arabia. this virus, namely mers-cov (middle east respiratory syndrome coronavirus), was classified within coronaviridae family, coronavirinae sub-family, bet ...201526313282
middle east respiratory syndrome coronavirus: transmission, virology and therapeutic targeting to aid in outbreak control.middle east respiratory syndrome coronavirus (mers-cov) causes high fever, cough, acute respiratory tract infection and multiorgan dysfunction that may eventually lead to the death of the infected individuals. mers-cov is thought to be transmitted to humans through dromedary camels. the occurrence of the virus was first reported in the middle east and it subsequently spread to several parts of the world. since 2012, about 1368 infections, including ~487 deaths, have been reported worldwide. nota ...201526315600
origin and possible genetic recombination of the middle east respiratory syndrome coronavirus from the first imported case in china: phylogenetics and coalescence analysis.the middle east respiratory syndrome coronavirus (mers-cov) causes a severe acute respiratory tract infection with a high fatality rate in humans. coronaviruses are capable of infecting multiple species and can evolve rapidly through recombination events. here, we report the complete genomic sequence analysis of a mers-cov strain imported to china from south korea. the imported virus, provisionally named chinagd01, belongs to group 3 in clade b in the whole-genome phylogenetic tree and also has ...201526350969
a highly immunogenic and protective middle east respiratory syndrome coronavirus vaccine based on a recombinant measles virus vaccine platform.in 2012, the first cases of infection with the middle east respiratory syndrome coronavirus (mers-cov) were identified. since then, more than 1,000 cases of mers-cov infection have been confirmed; infection is typically associated with considerable morbidity and, in approximately 30% of cases, mortality. currently, there is no protective vaccine available. replication-competent recombinant measles virus (mv) expressing foreign antigens constitutes a promising tool to induce protective immunity a ...201526355094
host-directed therapies for improving poor treatment outcomes associated with the middle east respiratory syndrome coronavirus infections.three years after its first discovery in jeddah saudi arabia, the novel zoonotic pathogen of humans, the middle east respiratory syndrome coronavirus (mers-cov) continues to be a major threat to global health security.(1) sporadic community acquired cases of mers continue to be reported from the middle east. the recent nosocomial outbreaks in hospitals in seoul, korea and at the national guard hospital in riyadh, saudi arabia indicate the epidemic potential of mers-cov. currently there are no ef ...201526365771
a humanized neutralizing antibody against mers-cov targeting the receptor-binding domain of the spike protein.the newly-emerging middle east respiratory syndrome coronavirus (mers-cov) can cause severe and fatal acute respiratory disease in humans. despite global efforts, the potential for an associated pandemic in the future cannot be excluded. the development of effective counter-measures is urgent. mers-cov-specific anti-viral drugs or vaccines are not yet available. using the spike receptor-binding domain of mers-cov (mers-rbd) to immunize mice, we identified two neutralizing monoclonal antibodies ( ...201526391698
the heptad repeat region is a major selection target in mers-cov and related coronaviruses.middle east respiratory syndrome coronavirus (mers-cov) originated in bats and spread to humans via zoonotic transmission from camels. we analyzed the evolution of the spike (s) gene in betacoronaviruses (betacovs) isolated from different mammals, in bat coronavirus populations, as well as in mers-cov strains from the current outbreak. results indicated several positively selected sites located in the region comprising the two heptad repeats (hr1 and hr2) and their linker. two sites (r652 and v1 ...201526404138
presence of antibodies but no evidence for circulation of mers-cov in dromedaries on the canary islands, 2015.in 2012, a new betacoronavirus, middle east respiratory syndrome coronavirus (mers-cov), was identified in humans. several studies confirmed dromedary camels to be a potential reservoir and a source for human infection. camels located on the canary islands were included in those studies and ca 10% of them were positive for mers-cov-specific antibodies. however, these findings could not be correctly interpreted because epidemiological information was not provided. thus, further investigations wer ...201526536463
kinetics of serologic responses to mers coronavirus infection in humans, south korea.we investigated the kinetics of serologic responses to middle east respiratory syndrome coronavirus (mers-cov) infection by using virus neutralization and mers-cov s1 igg elisa tests. in most patients, robust antibody responses developed by the third week of illness. delayed antibody responses with the neutralization test were associated with more severe disease.201526583829
asymptomatic mers-cov infection in humans possibly linked to infected dromedaries imported from oman to united arab emirates, may 2015.in may 2015 in united arab emirates, asymptomatic middle east respiratory syndrome coronavirus infection was identified through active case finding in 2 men with exposure to infected dromedaries. epidemiologic and virologic findings suggested zoonotic transmission. genetic sequences for viruses from the men and camels were similar to those for viruses recently detected in other countries.201526584223
inferring the hosts of coronavirus using dual statistical models based on nucleotide composition.many coronaviruses are capable of interspecies transmission. some of them have caused worldwide panic as emerging human pathogens in recent years, e.g., severe acute respiratory syndrome coronavirus (sars-cov) and middle east respiratory syndrome coronavirus (mers-cov). in order to assess their threat to humans, we explored to infer the potential hosts of coronaviruses using a dual-model approach based on nineteen parameters computed from spike genes of coronaviruses. both the support vector mac ...201526607834
an orthopoxvirus-based vaccine reduces virus excretion after mers-cov infection in dromedary camels.middle east respiratory syndrome coronavirus (mers-cov) infections have led to an ongoing outbreak in humans, which was fueled by multiple zoonotic mers-cov introductions from dromedary camels. in addition to the implementation of hygiene measures to limit further camel-to-human and human-to-human transmissions, vaccine-mediated reduction of mers-cov spread from the animal reservoir may be envisaged. here we show that a modified vaccinia virus ankara (mva) vaccine expressing the mers-cov spike p ...201626678878
bat origin of human coronaviruses.bats have been recognized as the natural reservoirs of a large variety of viruses. special attention has been paid to bat coronaviruses as the two emerging coronaviruses which have caused unexpected human disease outbreaks in the 21st century, severe acute respiratory syndrome coronavirus (sars-cov) and middle east respiratory syndrome coronavirus (mers-cov), are suggested to be originated from bats. various species of horseshoe bats in china have been found to harbor genetically diverse sars-li ...201526689940
coronaviruses: emerging and re-emerging pathogens in humans and animals.the severe acute respiratory syndrome coronavirus (sars-cov) and recently emerged middle east respiratory syndrome coronavirus (mers-cov) epidemics have proven the ability of coronaviruses to cross species barrier and emerge rapidly in humans. other coronaviruses such as porcine epidemic diarrhea virus (pedv) are also known to cause major disease epidemics in animals with huge economic loss. this special issue in virology journal aims to highlight the advances and key discoveries in the animal o ...201526690088
middle east respiratory syndrome coronavirus infection: virus-host cell interactions and implications on pathogenesis.middle-east respiratory syndrome coronavirus (mers-cov) was identified to cause severe respiratory infection in humans since 2012. the continuing mers epidemic with a case-fatality of more than 30% poses a major threat to public health worldwide. currently, the pathogenesis of human mers-cov infection remains poorly understood. we reviewed experimental findings from human primary cells and ex vivo human lung tissues, as well as those from animal studies, so as to understand the pathogenesis and ...201526690369
risk factors for primary middle east respiratory syndrome coronavirus illness in humans, saudi arabia, 2014.risk factors for primary middle east respiratory syndrome coronavirus (mers-cov) illness in humans are incompletely understood. we identified all primary mers-cov cases reported in saudi arabia during march-november 2014 by excluding those with history of exposure to other cases of mers-cov or acute respiratory illness of unknown cause or exposure to healthcare settings within 14 days before illness onset. using a case-control design, we assessed differences in underlying medical conditions and ...201626692185
an acute immune response to middle east respiratory syndrome coronavirus replication contributes to viral pathogenicity.middle east respiratory syndrome coronavirus (mers-cov) was first identified in a human with severe pneumonia in 2012. since then, infections have been detected in >1500 individuals, with disease severity ranging from asymptomatic to severe, fatal pneumonia. to elucidate the pathogenesis of this virus and investigate mechanisms underlying disease severity variation in the absence of autopsy data, a rhesus macaque and common marmoset model of mers-cov disease were analyzed. rhesus macaques develo ...201626724387
the roles of transportation and transportation hubs in the propagation of influenza and coronaviruses: a systematic review.respiratory viruses spread in humans across wide geographical areas in short periods of time, resulting in high levels of morbidity and mortality. we undertook a systematic review to assess the evidence that air, ground and sea mass transportation systems or hubs are associated with propagating influenza and coronaviruses.201626782122
middle east respiratory syndrome coronavirus intra-host populations are characterized by numerous high frequency variants.middle east respiratory syndrome coronavirus (mers-cov) is an emerging human pathogen related to sars virus. in vitro studies indicate this virus may have a broad host range suggesting an increased pandemic potential. genetic and epidemiological evidence indicate camels serve as a reservoir for mers virus but the mechanism of cross species transmission is unclear and many questions remain regarding the susceptibility of humans to infection. deep sequencing data was obtained from the nasal sample ...201626790002
clinicopathologic, immunohistochemical, and ultrastructural findings of a fatal case of middle east respiratory syndrome coronavirus infection in the united arab emirates, april 2014.middle east respiratory syndrome coronavirus (mers-cov) infection causes an acute respiratory illness and is associated with a high case fatality rate; however, the pathogenesis of severe and fatal mers-cov infection is unknown. we describe the histopathologic, immunohistochemical, and ultrastructural findings from the first autopsy performed on a fatal case of mers-cov in the world, which was related to a hospital outbreak in the united arab emirates in april 2014. the main histopathologic find ...201626857507
a comparative review of animal models of middle east respiratory syndrome coronavirus infection.middle east respiratory syndrome coronavirus (mers-cov) was initially isolated from a saudi arabian man with fatal pneumonia. since the original case in 2012, mers-cov infections have been reported in >1500 humans, and the case fatality rate is currently 35%. this lineage c betacoronavirus has been reported to cause a wide range of disease severity in humans, ranging from asymptomatic to progressive fatal pneumonia that may be accompanied by renal or multiorgan failure. although the clinical pre ...201626869154
differential expression of the middle east respiratory syndrome coronavirus receptor in the upper respiratory tracts of humans and dromedary camels.middle east respiratory syndrome coronavirus (mers-cov) is not efficiently transmitted between humans, but it is highly prevalent in dromedary camels. here we report that the mers-cov receptor--dipeptidyl peptidase 4 (dpp4)--is expressed in the upper respiratory tract epithelium of camels but not in that of humans. lack of dpp4 expression may be the primary cause of limited mers-cov replication in the human upper respiratory tract and hence restrict transmission.201626889022
middle east respiratory syndrome coronavirus (mers-cov): animal to human interaction.the middle east respiratory syndrome coronavirus (mers-cov) is a novel enzootic betacoronavirus that was first described in september 2012. the clinical spectrum of mers-cov infection in humans ranges from an asymptomatic or mild respiratory illness to severe pneumonia and multi-organ failure; overall mortality is around 35.7%. bats harbour several betacoronaviruses that are closely related to mers-cov but more research is needed to establish the relationship between bats and mers-cov. the serop ...201526924345
spread of mutant middle east respiratory syndrome coronavirus with reduced affinity to human cd26 during the south korean outbreak.the newly emerging middle east respiratory syndrome coronavirus (mers-cov) causes a severe respiratory infection with a high mortality rate (~35%). mers-cov has been a global threat due to continuous outbreaks in the arabian peninsula and international spread by infected travelers since 2012. from may to july 2015, a large outbreak initiated by an infected traveler from the arabian peninsula swept south korea and resulted in 186 confirmed cases with 38 deaths (case fatality rate, 20.4%). here, w ...201626933050
glycopeptide antibiotics potently inhibit cathepsin l in the late endosome/lysosome and block the entry of ebola virus, middle east respiratory syndrome coronavirus (mers-cov), and severe acute respiratory syndrome coronavirus (sars-cov).ebola virus infection can cause severe hemorrhagic fever with a high mortality in humans. the outbreaks of ebola viruses in 2014 represented the most serious ebola epidemics in history and greatly threatened public health worldwide. the development of additional effective anti-ebola therapeutic agents is therefore quite urgent. in this study, via high throughput screening of food and drug administration-approved drugs, we identified that teicoplanin, a glycopeptide antibiotic, potently prevents ...201626953343
Displaying items 1 - 100 of 317