coronavirus diversity, phylogeny and interspecies jumping.the sars epidemic has boosted interest in research on coronavirus biodiversity and genomics. before 2003, there were only 10 coronaviruses with complete genomes available. after the sars epidemic, up to december 2008, there was an addition of 16 coronaviruses with complete genomes sequenced. these include two human coronaviruses (human coronavirus nl63 and human coronavirus hku1), 10 other mammalian coronaviruses [bat sars coronavirus, bat coronavirus (bat-cov) hku2, bat-cov hku4, bat-cov hku5, ...200919546349
a mouse model for betacoronavirus subgroup 2c using a bat coronavirus strain hku5 variant.cross-species transmission of zoonotic coronaviruses (covs) can result in pandemic disease outbreaks. middle east respiratory syndrome cov (mers-cov), identified in 2012, has caused 182 cases to date, with ~43% mortality, and no small animal model has been reported. mers-cov and pipistrellus bat coronavirus (btcov) strain hku5 of betacoronavirus (β-cov) subgroup 2c share >65% identity at the amino acid level in several regions, including nonstructural protein 5 (nsp5) and the nucleocapsid (n) pr ...201424667706
identification of a novel coronavirus in bats.exotic wildlife can act as reservoirs of diseases that are endemic in the area or can be the source of new emerging diseases through interspecies transmission. the recent emergence of severe acute respiratory syndrome-associated coronavirus (sars-cov) highlights the importance of virus surveillance in wild animals. here, we report the identification of a novel bat coronavirus through surveillance of coronaviruses in wildlife. analyses of the rna sequence from the orf1b and s-gene regions indicat ...015681402
middle east respiratory syndrome coronavirus 4a protein is a double-stranded rna-binding protein that suppresses pact-induced activation of rig-i and mda5 in the innate antiviral response.middle east respiratory syndrome coronavirus (mers-cov) is an emerging pathogen that causes severe disease in human. mers-cov is closely related to bat coronaviruses hku4 and hku5. evasion of the innate antiviral response might contribute significantly to mers-cov pathogenesis, but the mechanism is poorly understood. in this study, we characterized mers-cov 4a protein as a novel immunosuppressive factor that antagonizes type i interferon production. mers-cov 4a protein contains a double-stranded ...201424522921
putative receptor binding domain of bat-derived coronavirus hku9 spike protein: evolution of betacoronavirus receptor binding motifs.the suggested bat origin for middle east respiratory syndrome coronavirus (mers-cov) has revitalized the studies of other bat-derived coronaviruses with respect to interspecies transmission potential. bat coronavirus (batcov) hku9 is an important betacoronavirus (betacov) that is phylogenetically affiliated with the same genus as mers-cov. the bat surveillance data indicated that batcov hku9 has been widely spreading and circulating in bats. this highlights the necessity of characterizing the vi ...201627696819
genomic characterization of a newly discovered coronavirus associated with acute respiratory distress syndrome in humans.a novel human coronavirus (hcov-emc/2012) was isolated from a man with acute pneumonia and renal failure in june 2012. this report describes the complete genome sequence, genome organization, and expression strategy of hcov-emc/2012 and its relation with known coronaviruses. the genome contains 30,119 nucleotides and contains at least 10 predicted open reading frames, 9 of which are predicted to be expressed from a nested set of seven subgenomic mrnas. phylogenetic analysis of the replicase gene ...201223170002
middle east respiratory syndrome coronavirus ns4b protein inhibits host rnase l activation.middle east respiratory syndrome coronavirus (mers-cov) is the first highly pathogenic human coronavirus to emerge since severe acute respiratory syndrome coronavirus (sars-cov) in 2002. like many coronaviruses, mers-cov carries genes that encode multiple accessory proteins that are not required for replication of the genome but are likely involved in pathogenesis. evasion of host innate immunity through interferon (ifn) antagonism is a critical component of viral pathogenesis. the ifn-inducible ...201627025250
molecular detection of viruses in kenyan bats and discovery of novel astroviruses, caliciviruses and rotaviruses.this is the first country-wide surveillance of bat-borne viruses in kenya spanning from 2012-2015 covering sites perceived to have medium to high level bat-human interaction. the objective of this surveillance study was to apply a non-invasive approach using fresh feces to detect viruses circulating within the diverse species of kenyan bats. we screened for both dna and rna viruses; specifically, astroviruses (astvs), adenoviruses (advs), caliciviruses (calvs), coronaviruses (covs), flaviviruses ...201728393313
recent transmission of a novel alphacoronavirus, bat coronavirus hku10, from leschenault's rousettes to pomona leaf-nosed bats: first evidence of interspecies transmission of coronavirus between bats of different suborders.although coronaviruses are known to infect various animals by adapting to new hosts, interspecies transmission events are still poorly understood. during a surveillance study from 2005 to 2010, a novel alphacoronavirus, batcov hku10, was detected in two very different bat species, ro-batcov hku10 in leschenault's rousettes (rousettus leschenaulti) (fruit bats in the suborder megachiroptera) in guangdong and hi-batcov hku10 in pomona leaf-nosed bats (hipposideros pomona) (insectivorous bats in th ...201222933277
a sars-like cluster of circulating bat coronaviruses shows potential for human emergence.the emergence of severe acute respiratory syndrome coronavirus (sars-cov) and middle east respiratory syndrome (mers)-cov underscores the threat of cross-species transmission events leading to outbreaks in humans. here we examine the disease potential of a sars-like virus, shc014-cov, which is currently circulating in chinese horseshoe bat populations. using the sars-cov reverse genetics system, we generated and characterized a chimeric virus expressing the spike of bat coronavirus shc014 in a m ...201526552008
isolation and characterization of a novel bat coronavirus closely related to the direct progenitor of severe acute respiratory syndrome coronavirus.we report the isolation and characterization of a novel bat coronavirus which is much closer to the severe acute respiratory syndrome coronavirus (sars-cov) in genomic sequence than others previously reported, particularly in its s gene. cell entry and susceptibility studies indicated that this virus can use ace2 as a receptor and infect animal and human cell lines. our results provide further evidence of the bat origin of the sars-cov and highlight the likelihood of future bat coronavirus emerg ...201526719272
sars-unique fold in the rousettus bat coronavirus hku9.the coronavirus nonstructural protein 3 (nsp3) is a multifunctional protein that comprises multiple structural domains. this protein assists viral polyprotein cleavage, host immune interference, and may play other roles in genome replication or transcription. here, we report the solution nmr structure of a protein from the "sars-unique region" of the bat coronavirus hku9. the protein contains a frataxin fold or double-wing motif, which is an α + β fold that is associated with protein/protein int ...201728580734
[a novel coronavirus, mers-cov].a novel human coronavirus was identified in saudi arabia and qatar as the causative agent of severe acute respiratory diseases in 2012. the virus was termed middle east respiratory syndrome coronavirus (mers-cov) and is taken notice of important coronavirus caused severe diseases to human after the outbreak of severe acute respiratory syndrome (sars) coronavirus. there is a lot of unknown characterization regarding mers-cov because of less than one year after finding the first case. mers-cov was ...201324769571
genetic characterization of betacoronavirus lineage c viruses in bats reveals marked sequence divergence in the spike protein of pipistrellus bat coronavirus hku5 in japanese pipistrelle: implications for the origin of the novel middle east respiratory syndrome coronavirus.while the novel middle east respiratory syndrome coronavirus (mers-cov) is closely related to tylonycteris bat cov hku4 (ty-batcov hku4) and pipistrellus bat cov hku5 (pi-batcov hku5) in bats from hong kong, and other potential lineage c betacoronaviruses in bats from africa, europe, and america, its animal origin remains obscure. to better understand the role of bats in its origin, we examined the molecular epidemiology and evolution of lineage c betacoronaviruses among bats. ty-batcov hku4 and ...201323720729
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
from sars to mers: crystallographic studies on coronaviral proteases enable antiviral drug design.this review focuses on the important contributions that macromolecular crystallography has made over the past 12 years to elucidating structures and mechanisms of the essential proteases of coronaviruses, the main protease (m(pro) ) and the papain-like protease (pl(pro) ). the role of x-ray crystallography in structure-assisted drug discovery against these targets is discussed. aspects dealt with in this review include the emergence of the sars coronavirus in 2002-2003 and of the mers coronaviru ...201425039866
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
bat origins of mers-cov supported by bat coronavirus hku4 usage of human receptor cd26.the recently reported middle east respiratory syndrome coronavirus (mers-cov) is phylogenetically closely related to the bat coronaviruses (batcovs) hku4 and hku5. however, the evolutionary pathway of mers-cov is still unclear. a receptor binding domain (rbd) in the mers-cov envelope-embedded spike protein specifically engages human cd26 (hcd26) to initiate viral entry. the high sequence identity in the viral spike protein prompted us to investigate if hku4 and hku5 can recognize hcd26 for cell ...201425211075
two mutations were critical for bat-to-human transmission of middle east respiratory syndrome 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
targeting zoonotic viruses: structure-based inhibition of the 3c-like protease from bat coronavirus hku4--the likely reservoir host to the human coronavirus that causes middle east respiratory syndrome (mers).the bat coronavirus hku4 belongs to the same 2c lineage as that of the deadly middle east respiratory syndrome coronavirus (mers-cov) and shows high sequence similarity, therefore potentiating a threat to the human population through a zoonotic shift or 'spill over' event. to date, there are no effective vaccines or antiviral treatments available that are capable of limiting the pathogenesis of any human coronaviral infection. an attractive target for the development of anti-coronaviral therapeu ...201526190463
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
a bat-derived putative cross-family recombinant coronavirus with a reovirus gene.the emergence of severe acute respiratory syndrome coronavirus (sars-cov) in 2002 and middle east respiratory syndrome coronavirus (mers-cov) in 2012 has generated enormous interest in the biodiversity, genomics and cross-species transmission potential of coronaviruses, especially those from bats, the second most speciose order of mammals. herein, we identified a novel coronavirus, provisionally designated rousettus bat coronavirus gccdc1 (ro-batcov gccdc1), in the rectal swab samples of rousett ...201627676249
efficient reverse genetic systems for rapid genetic manipulation of emergent and preemergent infectious coronaviruses.emergent and preemergent coronaviruses (covs) pose a global threat that requires immediate intervention. rapid intervention necessitates the capacity to generate, grow, and genetically manipulate infectious covs in order to rapidly evaluate pathogenic mechanisms, host and tissue permissibility, and candidate antiviral therapeutic efficacy. covs encode the largest viral rna genomes at about 28-32,000 nucleotides in length, and thereby complicate efficient engineering of the genome. deconstructing ...201728508214
coexistence of different genotypes in the same bat and serological characterization of rousettus bat coronavirus hku9 belonging to a novel betacoronavirus subgroup.rousettus bat coronavirus hku9 (ro-batcov hku9), a recently identified coronavirus of novel betacoronavirus subgroup d, from leschenault's rousette, was previously found to display marked sequence polymorphism among genomes of four strains. among 10 bats with complete rna-dependent rna polymerase (rdrp), spike (s), and nucleocapsid (n) genes sequenced, three and two sequence clades for all three genes were codetected in two and five bats, respectively, suggesting the coexistence of two or three ...201020702646
bat coronaviruses and experimental infection of bats, the philippines.fifty-two bats captured during july 2008 in the philippines were tested by reverse transcription-pcr to detect bat coronavirus (cov) rna. the overall prevalence of virus rna was 55.8%. we found 2 groups of sequences that belonged to group 1 (genus alphacoronavirus) and group 2 (genus betacoronavirus) covs. phylogenetic analysis of the rna-dependent rna polymerase gene showed that groups 1 and 2 covs were similar to bat-cov/china/a515/2005 (95% nt sequence identity) and bat-cov/hku9-1/china/2007 ...201020678314
ecoepidemiology and complete genome comparison of different strains of severe acute respiratory syndrome-related rhinolophus bat coronavirus in china reveal bats as a reservoir for acute, self-limiting infection that allows recombination events.despite the identification of severe acute respiratory syndrome-related coronavirus (sarsr-cov) in rhinolophus chinese horseshoe bats (sarsr-rh-batcov) in china, the evolutionary and possible recombination origin of sarsr-cov remains undetermined. we carried out the first study to investigate the migration pattern and sarsr-rh-batcov genome epidemiology in chinese horseshoe bats during a 4-year period. of 1,401 chinese horseshoe bats from hong kong and guangdong, china, that were sampled, sarsr- ...201020071579
covdb: a comprehensive database for comparative analysis of coronavirus genes and genomes.the recent sars epidemic has boosted interest in the discovery of novel human and animal coronaviruses. by july 2007, more than 3000 coronavirus sequence records, including 264 complete genomes, are available in genbank. the number of coronavirus species with complete genomes available has increased from 9 in 2003 to 25 in 2007, of which six, including coronavirus hku1, bat sars coronavirus, group 1 bat coronavirus hku2, groups 2c and 2d coronaviruses, were sequenced by our laboratory. to overco ...200817913743
cross-reactive antibodies in convalescent sars patients' sera against the emerging novel human coronavirus emc (2012) by both immunofluorescent and neutralizing antibody tests.a severe acute respiratory syndrome (sars)-like disease due to a novel betacoronavirus, human coronavirus emc (hcov-emc), has emerged recently. hcov-emc is phylogenetically closely related to tylonycteris-bat-coronavirus-hku4 and pipistrellus-bat-coronavirus-hku5 in hong kong. we conducted a seroprevalence study on archived sera from 94 game-food animal handlers at a wild life market, 28 sars patients, and 152 healthy blood donors in southern china to assess the zoonotic potential and evidence f ...201323583636
receptor usage of a novel bat lineage c betacoronavirus reveals evolution of mers-related coronavirus spike proteins for human dpp4 binding.although bats are known to harbor mers-cov-related viruses, the role of bats in the evolutionary origin and pathway remains obscure. we identified a novel mers-cov-related betacoronavirus, hp-batcov hku25, from chinese pipistrelle bats. while being closely related to mers-cov in most genome regions, its spike protein occupies a phylogenetic position between that of ty-batcov hku4 and pi-batcov hku5. since ty-batcov hku4 but not pi-batcov hku5 can utilize mers-cov receptor, hdpp4, for cell entry, ...201829346682
discovery of a novel swine enteric alphacoronavirus (seacov) in southern china.outbreaks of diarrhea in newborn piglets without detection of transmissible gastroenteritis virus (tgev), porcine epidemic diarrhea virus (pedv) and porcine deltacoronavirus (pdcov), have been recorded in a pig farm in southern china since february 2017. isolation and propagation of the pathogen in cell culture resulted in discovery of a novel swine enteric alphacoronavirus (tentatively named seacov) related to the bat coronavirus hku2 identified in the same region a decade ago. specific fluores ...201729102111
detection of alpha- and betacoronaviruses in rodents from yunnan, china.rodents represent the most diverse mammals on the planet and are important reservoirs of human pathogens. coronaviruses infect various animals, but to date, relatively few coronaviruses have been identified in rodents worldwide. the evolution and ecology of coronaviruses in rodent have not been fully investigated.201728549438
genetic relatedness of the novel human group c betacoronavirus to tylonycteris bat coronavirus hku4 and pipistrellus bat coronavirus hku5.the recent outbreak of severe respiratory infections associated with a novel group c betacoronavirus (hcov-emc) from saudi arabia has drawn global attention to another highly probable "sars-like" animal-to-human interspecies jumping event in coronavirus (cov). the genome of hcov-emc is most closely related to tylonycteris bat coronavirus hku4 (ty-batcov hku4) and pipistrellus bat coronavirus hku5 (pi-batcov hku5) we discovered in 2006. phylogenetically, hcov-emc is clustered with ty-batcov hku4/ ...201226038405
genomic and serological detection of bat coronavirus from bats in the philippines.bat coronavirus (btcov) is assumed to be a progenitor of severe acute respiratory syndrome (sars)-related coronaviruses. to explore the distribution of btcovs in the philippines, we collected 179 bats and detected viral rna from intestinal or fecal samples by rt-pcr. the overall prevalence of btcovs among bats was 29.6 %. phylogenetic analysis of the partial rna-dependent rna polymerase gene suggested that one of the detected btcovs was a novel alphacoronavirus, while the others belonged to the ...201222833101
comparative analysis of twelve genomes of three novel group 2c and group 2d coronaviruses reveals unique group and subgroup features.twelve complete genomes of three novel coronaviruses-bat coronavirus hku4 (bat-cov hku4), bat-cov hku5 (putative group 2c), and bat-cov hku9 (putative group 2d)-were sequenced. comparative genome analysis showed that the various open reading frames (orfs) of the genomes of the three coronaviruses had significantly higher amino acid identities to those of other group 2 coronaviruses than group 1 and 3 coronaviruses. phylogenetic trees constructed using chymotrypsin-like protease, rna-dependent rn ...200717121802
prevalence and genetic diversity of coronaviruses in bats from china.coronaviruses can infect a variety of animals including poultry, livestock, and humans and are currently classified into three groups. the interspecies transmissions of coronaviruses between different hosts form a complex ecosystem of which little is known. the outbreak of severe acute respiratory syndrome (sars) and the recent identification of new coronaviruses have highlighted the necessity for further investigation of coronavirus ecology, in particular the role of bats and other wild animals ...200616840328
coronavirus infection and diversity in bats in the australasian region.following the sars outbreak, extensive surveillance was undertaken globally to detect and identify coronavirus diversity in bats. this study sought to identify the diversity and prevalence of coronaviruses in bats in the australasian region. we identified four different genotypes of coronavirus, three of which (an alphacoronavirus and two betacoronaviruses) are potentially new species, having less than 90% nucleotide sequence identity with the most closely related described viruses. we did not d ...201627048154
complete genome sequence of bat coronavirus hku2 from chinese horseshoe bats revealed a much smaller spike gene with a different evolutionary lineage from the rest of the genome.apart from bat-sars-cov, we have identified a novel group 1 coronavirus, bat-cov hku2, in rhinolophus sinicus (chinese horseshoe bats). since it has been suggested that the receptor-binding motif (rbm) of sars-cov may have been acquired from a group 1 coronavirus, we conducted a surveillance study and identified bat-sars-cov and bat-cov hku2 in 8.7% and 7.5% respectively of r. sinicus in hong kong and guangdong. complete genome sequencing of four strains of bat-cov hku2 revealed the smallest cor ...200717617433
genetic characteristics of coronaviruses from korean bats in 2016.bats have increasingly been recognized as the natural reservoir of severe acute respiratory syndrome (sars), coronavirus, and other coronaviruses found in mammals. however, little research has been conducted on bat coronaviruses in south korea. in this study, bat samples (332 oral swabs, 245 fecal samples, 38 urine samples, and 57 bat carcasses) were collected at 33 natural bat habitat sites in south korea. rt-pcr and sequencing were performed for specific coronavirus genes to identify the bat c ...201728725945
bat coronavirus in brazil related to appalachian ridge and porcine epidemic diarrhea viruses. 201525811911
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
conserved antigenic sites between mers-cov and bat-coronavirus are revealed through sequence analysis.mers-cov is a newly emerged human coronavirus reported closely related with hku4 and hku5 bat coronaviruses. bat and mers corona-viruses are structurally related. therefore, it is of interest to estimate the degree of conserved antigenic sites among them. it is of importance to elucidate the shared antigenic-sites and extent of conservation between them to understand the evolutionary dynamics of mers-cov.201626962326
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