| sars coronavirus papain-like protease induces egr-1-dependent up-regulation of tgf-β1 via ros/p38 mapk/stat3 pathway. | sars coronavirus (sars-cov) papain-like protease (plpro) has been identified in tgf-β1 up-regulation in human promonocytes (proteomics 2012, 12: 3193-205). this study investigates the mechanisms of sars-cov plpro-induced tgf-β1 promoter activation in human lung epithelial cells and mouse models. sars-cov plpro dose- and time-dependently up-regulates tgf-β1 and vimentin in a549 cells. dual luciferase reporter assays with tgf-β1 promoter plasmids indicated that tgf-β1 promoter region between -175 ... | 2016 | 27173006 |
| kanyawara virus: a novel rhabdovirus infecting newly discovered nycteribiid bat flies infesting previously unknown pteropodid bats in uganda. | bats are natural reservoir hosts of highly virulent pathogens such as marburg virus, nipah virus, and sars coronavirus. however, little is known about the role of bat ectoparasites in transmitting and maintaining such viruses. the intricate relationship between bats and their ectoparasites suggests that ectoparasites might serve as viral vectors, but evidence to date is scant. bat flies, in particular, are highly specialized obligate hematophagous ectoparasites that incidentally bite humans. usi ... | 2017 | 28706276 |
| protection from sars coronavirus conferred by live measles vaccine expressing the spike glycoprotein. | the recent identification of a novel human coronavirus responsible of a sars-like illness in the middle-east a decade after the sars pandemic, demonstrates that reemergence of a sars-like coronavirus from an animal reservoir remains a credible threat. because sars is contracted by aerosolized contamination of the respiratory tract, a vaccine inducing mucosal long-term protection would be an asset to control new epidemics. to this aim, we generated live attenuated recombinant measles vaccine (mv) ... | 2014 | 24606680 |
| discovery of a highly divergent coronavirus in the asian house shrew from china illuminates the origin of the alphacoronaviruses. | although shrews are one of the largest groups of mammals little is known about their role in the evolution and transmission of viral pathogens including coronaviruses. we captured 266 asian house shrews (suncus murinus) in jiangxi and zhejiang provinces, china, during 2013-2015. coronavirus (cov) rna was detected in 24 asian house shrews, with an overall prevalence of 9.02%. complete viral genome sequences were successfully recovered from the rna positive samples. the newly discovered shrew cov ... | 2017 | 28637760 |
| t-cell immunity of sars-cov: implications for vaccine development against mers-cov. | over 12 years have elapsed since severe acute respiratory syndrome (sars) triggered the first global alert for coronavirus infections. virus transmission in humans was quickly halted by public health measures and human infections of sars coronavirus (sars-cov) have not been observed since. however, other coronaviruses still pose a continuous threat to human health, as exemplified by the recent emergence of middle east respiratory syndrome (mers) in humans. the work on sars-cov widens our knowled ... | 2017 | 27840203 |
| alisporivir inhibits mers- and sars-coronavirus replication in cell culture, but not sars-coronavirus infection in a mouse model. | currently, there is no registered treatment for infections with emerging zoonotic coronaviruses like sars- and mers-coronavirus. we here report that in cultured cells low-micromolar concentrations of alisporivir, a non-immunosuppressive cyclosporin a-analog, inhibit the replication of four different coronaviruses, including mers- and sars-coronavirus. ribavirin was found to further potentiate the antiviral effect of alisporivir in these cell culture-based infection models, but this combination t ... | 2017 | 27840112 |
| 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 ... | 2016 | 27676249 |
| abelson kinase inhibitors are potent inhibitors of severe acute respiratory syndrome coronavirus and middle east respiratory syndrome coronavirus fusion. | the highly pathogenic severe acute respiratory syndrome coronavirus (sars-cov) and middle east respiratory syndrome coronavirus (mers-cov) cause significant morbidity and morality. there is currently no approved therapeutic for highly pathogenic coronaviruses, even as mers-cov is spreading throughout the middle east. we previously screened a library of fda-approved drugs for inhibitors of coronavirus replication in which we identified abelson (abl) kinase inhibitors, including the anticancer dru ... | 2016 | 27466418 |
| development of monoclonal antibody and diagnostic test for middle east respiratory syndrome coronavirus using cell-free synthesized nucleocapsid antigen. | protein nativity is one of the most critical factors for the quality of antigens used as immunogens and the reactivities of the resultant antibodies. the preparation and purification of native viral antigens in conventional cell-based protein expression systems are often accompanied by technical hardships. these challenges are attributable mainly to protein aggregation and insolubility during expression and purification, as well as to very low expression levels associated with the toxicity of so ... | 2016 | 27148198 |
| genetic diversity of coronaviruses in miniopterus fuliginosus bats. | coronaviruses, such as severe acute respiratory syndrome coronavirus and middle east respiratory syndrome coronavirus, pose significant public health threats. bats have been suggested to act as natural reservoirs for both these viruses, and periodic monitoring of coronaviruses in bats may thus provide important clues about emergent infectious viruses. the eastern bent-wing bat miniopterus fuliginosus is distributed extensively throughout china. we therefore analyzed the genetic diversity of coro ... | 2016 | 27125516 |
| development of a sars coronavirus vaccine from recombinant spike protein plus delta inulin adjuvant. | given periodic outbreaks of fatal human infections caused by coronaviruses, development of an optimal coronavirus vaccine platform capable of rapid production is an ongoing priority. this chapter describes the use of an insect cell expression system for rapid production of a recombinant vaccine against severe acute respiratory syndrome coronavirus (sars). detailed methods are presented for expression, purification, and release testing of sars recombinant spike protein antigen, followed by adjuva ... | 2016 | 27076136 |
| memory t cell responses targeting the sars coronavirus persist up to 11 years post-infection. | severe acute respiratory syndrome (sars) is a highly contagious infectious disease which first emerged in late 2002, caused by a then novel human coronavirus, sars coronavirus (sars-cov). the virus is believed to have originated from bats and transmitted to human through intermediate animals such as civet cats. the re-emergence of sars-cov remains a valid concern due to the continual persistence of zoonotic sars-covs and sars-like covs (sl-covs) in bat reservoirs. in this study, the screening fo ... | 2016 | 26954467 |
| 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 ... | 2016 | 26953343 |
| comparative epidemiology of human infections with middle east respiratory syndrome and severe acute respiratory syndrome coronaviruses among healthcare personnel. | the largest nosocomial outbreak of middle east respiratory syndrome (mers) occurred in south korea in 2015. health care personnel (hcp) are at high risk of acquiring mers-coronavirus (mers-cov) infections, similar to the severe acute respiratory syndrome (sars)-coronavirus (sars-cov) infections first identified in 2003. this study described the similarities and differences in epidemiological and clinical characteristics of 183 confirmed global mers cases and 98 sars cases in taiwan associated wi ... | 2016 | 26930074 |
| 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 ... | 2016 | 26790002 |
| development of animal models against emerging coronaviruses: from sars to mers coronavirus. | two novel coronaviruses have emerged to cause severe disease in humans. while bats may be the primary reservoir for both viruses, sars coronavirus (sars-cov) likely crossed into humans from civets in china, and mers coronavirus (mers-cov) has been transmitted from camels in the middle east. unlike sars-cov that resolved within a year, continued introductions of mers-cov present an on-going public health threat. animal models are needed to evaluate countermeasures against emerging viruses. with s ... | 2015 | 25791336 |
| novel respiratory viruses: what should the clinician be alert for? | since 1990, several novel respiratory viruses affecting humans have been described. in this review, we focus on three pathogens that have caused significant human mortality and raise important public health concerns: severe acute respiratory syndrome (sars)-coronavirus, middle east respiratory syndrome (mers)-coronavirus and avian influenza a viruses (h5n1 and h7n9). novel respiratory viruses have the potential to instil fear in the public and physicians alike if they are associated with a high ... | 2014 | 25468912 |
| insights into rna synthesis, capping, and proofreading mechanisms of sars-coronavirus. | the successive emergence of highly pathogenic coronaviruses (covs) such as the severe acute respiratory syndrome (sars-cov) in 2003 and the middle east respiratory syndrome coronavirus (mers-cov) in 2012 has stimulated a number of studies on the molecular biology. this research has provided significant new insight into functions and activities of the replication/transcription multi-protein complex. the latter directs both continuous and discontinuous rna synthesis to replicate and transcribe the ... | 2014 | 25451065 |
| molecular pathology of emerging coronavirus infections. | respiratory viruses can cause a wide spectrum of pulmonary diseases, ranging from mild, upper respiratory tract infections to severe and life-threatening lower respiratory tract infections, including the development of acute lung injury (ali) and acute respiratory distress syndrome (ards). viral clearance and subsequent recovery from infection require activation of an effective host immune response; however, many immune effector cells may also cause injury to host tissues. severe acute respirato ... | 2015 | 25270030 |
| 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 ... | 2014 | 25039866 |
| the effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis. | administration of convalescent plasma, serum, or hyperimmune immunoglobulin may be of clinical benefit for treatment of severe acute respiratory infections (saris) of viral etiology. we conducted a systematic review and exploratory meta-analysis to assess the overall evidence. | 2015 | 25030060 |
| crystal structure of the papain-like protease of mers coronavirus reveals unusual, potentially druggable active-site features. | the middle-east respiratory syndrome coronavirus (mers-cov) causes severe acute pneumonia and renal failure. the mers-cov papain-like protease (pl(pro)) is a potential target for the development of antiviral drugs. to facilitate these efforts, we determined the three-dimensional structure of the enzyme by x-ray crystallography. the molecule consists of a ubiquitin-like domain and a catalytic core domain. the catalytic domain displays an extended right-hand fold with a zinc ribbon and embraces a ... | 2014 | 24992731 |
| serological assays for emerging coronaviruses: challenges and pitfalls. | more than a decade after the emergence of severe acute respiratory syndrome coronavirus (sars-cov) in 2002/2003 the occurrence of a novel cov termed middle east respiratory syndrome (mers) cov challenges researchers and public health authorities. to control spread and finally contain novel viruses, rapid identification and subsequent isolation of infected individuals and their contacts is of utmost importance. next to methods for nucleic acid detection, validated serological assays are particula ... | 2014 | 24670324 |
| in-vitro renal epithelial cell infection reveals a viral kidney tropism as a potential mechanism for acute renal failure during middle east respiratory syndrome (mers) coronavirus infection. | the middle east respiratory syndrome coronavirus (mers-cov) causes symptoms similar to severe acute respiratory syndrome coronavirus (sars-cov), yet involving an additional component of acute renal failure (arf) according to several published case reports. impairment of the kidney is not typically seen in coronavirus infections. the role of kidney infection in mers is not understood. | 2013 | 24364985 |
| active replication of middle east respiratory syndrome coronavirus and aberrant induction of inflammatory cytokines and chemokines in human macrophages: implications for pathogenesis. | middle east respiratory syndrome coronavirus (mers-cov) infection caused severe pneumonia and multiorgan dysfunction and had a higher crude fatality rate (around 50% vs. 10%) than sars coronavirus (sars-cov) infection. to understand the pathogenesis, we studied viral replication, cytokine/chemokine response, and antigen presentation in mers-cov-infected human monocyte-derived macrophages (mdms) versus sars-cov-infected mdms. only mers-cov can replicate in mdms. both viruses were unable to signif ... | 2014 | 24065148 |
| receptor recognition and cross-species infections of sars coronavirus. | receptor recognition is a major determinant of the host range, cross-species infections, and pathogenesis of the severe acute respiratory syndrome coronavirus (sars-cov). a defined receptor-binding domain (rbd) in the sars-cov spike protein specifically recognizes its host receptor, angiotensin-converting enzyme 2 (ace2). this article reviews the latest knowledge about how rbds from different sars-cov strains interact with ace2 from several animal species. detailed research on these rbd/ace2 int ... | 2013 | 23994189 |
| therapeutic options for middle east respiratory syndrome coronavirus (mers-cov)--possible lessons from a systematic review of sars-cov therapy. | the middle east respiratory syndrome coronavirus (mers-cov) has been detected in a number of countries in the middle east and europe with an apparently high mortality rate. it is phylogenetically related to the sars coronavirus and has also been associated with severe respiratory illness as well as nosocomial transmission in healthcare settings. current international recommendations do not support any specific therapies; however, there are a number of agents, which were used during the sars epid ... | 2013 | 23993766 |
| receptor-binding domain as a target for developing sars vaccines. | a decade ago, severe acute respiratory syndrome (sars) coronavirus (sars-cov) caused a global pandemic with a mortality rate of 10%. reports of recent outbreaks of a sars-like disease caused by middle east respiratory syndrome coronavirus (mers-cov) have raised serious concerns of a possible reemergence of sars-cov, either by laboratory escape or the presence of a natural reservoir. therefore, the development of effective and safe sars vaccines is still needed. based on our previous studies, we ... | 2013 | 23977435 |
| 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 ... | 2013 | 23977431 |
| 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 ... | 2013 | 23977431 |
| [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 ... | 2013 | 24769571 |
| prevention and treatment of viral respiratory infections by traditional chinese herbs. | this review focuses on current knowledge of traditional chinese herbs on prevention and treatment of viral respiratory infections, especially caused by severe acute respiratory syndromes (sars) virus, respiratory syncytial virus (rsv) and influenza viruses. | 2014 | 24709192 |
| infection prevention and control measures for acute respiratory infections in healthcare settings: an update. | viruses account for the majority of the acute respiratory tract infections (aris) globally with a mortality exceeding 4 million deaths per year. the most commonly encountered viruses, in order of frequency, include influenza, respiratory syncytial virus, parainfluenza and adenovirus. current evidence suggests that the major mode of transmission of arls is through large droplets, but transmission through contact (including hand contamination with subsequent self-inoculation) and infectious respir ... | 2013 | 23888794 |
| in silico analysis of the cyanobacterial lectin scytovirin: new insights into binding properties. | scytovirin is a lectin isolated from the cyanobacterium scytonema varium that has shown activity against hiv, sars coronavirus and zaire ebola virus. its 95 amino acids are divided into two structural domains (sd), the first spanning amino acids 1-48 (sd1) and the second 49-95 (sd2). interestingly, the domains are nearly identical but differ in their affinities for carbohydrates. with the aim of enhancing understanding of the binding properties of scytovirin, we performed molecular dynamics (md) ... | 2017 | 28756560 |
| comprehensive structural analysis of designed incomplete polypeptide chains of the replicase nonstructural protein 1 from the severe acute respiratory syndrome coronavirus. | the cotranslational folding is recognized as a very cooperative process that occurs after the nearly completion of the polypeptide sequence of a domain. here we investigated the challenges faced by polypeptide segments of a non-vectorial β-barrel fold. besides the biological interest behind the sars coronavirus non-structural protein 1 (nsp1, 117 amino acids), this study model has two structural features that motivated its use in this work: 1- its recombinant production is dependent on the tempe ... | 2017 | 28750053 |
| two-amino acids change in the nsp4 of sars coronavirus abolishes viral replication. | infection with coronavirus rearranges the host cell membrane to assemble a replication/transcription complex in which replication of the viral genome and transcription of viral mrna occur. although coexistence of nsp3 and nsp4 is known to cause membrane rearrangement, the mechanisms underlying the interaction of these two proteins remain unclear. we demonstrated that binding of nsp4 with nsp3 is essential for membrane rearrangement and identified amino acid residues in nsp4 responsible for the i ... | 2017 | 28738245 |
| role of fomites in sars transmission during the largest hospital outbreak in hong kong. | the epidemic of severe acute respiratory syndrome (sars) had a significant effect on global society in the early 2000s and the potential of its resurgence exists. studies on the modes of transmission of sars are limited though a number of outbreak studies have revealed the possible airborne route. to develop more specific and effective control strategies, we conducted a detailed mechanism-based investigation that explored the role of fomite transmission in the well-known ward 8a outbreak. we con ... | 2017 | 28727803 |
| toward the identification of viral cap-methyltransferase inhibitors by fluorescence screening assay. | two highly pathogenic human coronaviruses associated with severe respiratory syndromes emerged since the beginning of the century. the severe acute respiratory syndrome sars-coronavirus (cov) spread first in southern china in 2003 with about 8000 infected cases in few months. then in 2012, the middle east respiratory syndrome (mers-cov) emerged from the arabian peninsula giving a still on-going epidemic associated to a high fatality rate. covs are thus considered a major health threat. this is e ... | 2017 | 28676301 |
| targeting endosomal acidification by chloroquine analogs as a promising strategy for the treatment of emerging viral diseases. | emerging viruses such as hiv, dengue, influenza a, sars coronavirus, ebola, and other viruses pose a significant threat to human health. majority of these viruses are responsible for the outbreaks of pathogenic lethal infections. to date, there are no effective therapeutic strategies available for the prophylaxis and treatment of these infections. chloroquine analogs have been used for decades as the primary and most successful drugs against malaria. concomitant with the emergence of chloroquine ... | 2017 | 28596841 |
| allelic variation in the toll-like receptor adaptor protein ticam2 contributes to sars-coronavirus pathogenesis in mice. | host genetic variation is known to contribute to differential pathogenesis following infection. mouse models allow direct assessment of host genetic factors responsible for susceptibility to severe acute respiratory syndrome coronavirus (sars-cov). based on an assessment of early stage lines from the collaborative cross mouse multi-parent population, we identified two lines showing highly divergent susceptibilities to sars-cov: the resistant cc003/unc and the susceptible cc053/unc. we generated ... | 2017 | 28592648 |
| 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 ... | 2017 | 28580734 |
| optimization of the production process and characterization of the yeast-expressed sars-cov recombinant receptor-binding domain (rbd219-n1), a sars vaccine candidate. | from 2002 to 2003, a global pandemic of severe acute respiratory syndrome (sars) spread to 5 continents and caused 8000 respiratory infections and 800 deaths. to ameliorate the effects of future outbreaks as well as to prepare for biodefense, a process for the production of a recombinant protein vaccine candidate is under development. previously, we reported the 5 l scale expression and purification of a promising recombinant sars vaccine candidate, rbd219-n1, the 218-amino acid residue receptor ... | 2017 | 28456726 |
| sars coronavirus papain-like protease up-regulates the collagen expression through non-samd tgf-β1 signaling. | sars coronavirus (cov) papain-like protease (plpro) reportedly induced the production of tgf-β1 through p38 mapk/stat3-meidated egr-1-dependent activation (sci. rep. 6, 25754). this study investigated the correlation of plpro-induced tgf-β1 with the expression of type i collagen in human lung epithelial cells and mouse pulmonary tissues. specific inhibitors for tgf-βri, p38 mapk, mek, and stat3 proved that sars-cov plpro induced tgf-β1-dependent up-regulation of type i collagen in vitro and in v ... | 2017 | 28414040 |
| the role of epidermal growth factor receptor (egfr) signaling in sars coronavirus-induced pulmonary fibrosis. | many survivors of the 2003 outbreak of severe acute respiratory syndrome (sars) developed residual pulmonary fibrosis with increased severity seen in older patients. autopsies of patients that died from sars also showed fibrosis to varying extents. pulmonary fibrosis can be occasionally seen as a consequence to several respiratory viral infections but is much more common after a sars coronavirus (sars-cov) infection. given the threat of future outbreaks of severe coronavirus disease, including m ... | 2017 | 28390872 |
| characterization and phylogenetic analysis of new bat astroviruses detected in gabon, central africa. | astroviruses are emerging rna viruses that cause enteropathogenic infections in humans and in other mammals. the identification of astroviruses in a wide range of animals highlights the zoonotic importance of these viruses. bats can harbor many different viruses, among which some are highly pathogenic for humans (for instance, nipah, ebola and sars coronavirus), and also several astroviruses. as some rna viruses can be directly transmitted from bats to humans, it is crucial to collect data about ... | 2017 | 27928918 |
| the effect of inhibition of pp1 and tnfα signaling on pathogenesis of sars coronavirus. | the complex interplay between viral replication and host immune response during infection remains poorly understood. while many viruses are known to employ anti-immune strategies to facilitate their replication, highly pathogenic virus infections can also cause an excessive immune response that exacerbates, rather than reduces pathogenicity. to investigate this dichotomy in severe acute respiratory syndrome coronavirus (sars-cov), we developed a transcriptional network model of sars-cov infectio ... | 2016 | 27663205 |
| immunodominant sars coronavirus epitopes in humans elicited both enhancing and neutralizing effects on infection in non-human primates. | severe acute respiratory syndrome (sars) is caused by a coronavirus (sars-cov) and has the potential to threaten global public health and socioeconomic stability. evidence of antibody-dependent enhancement (ade) of sars-cov infection in vitro and in non-human primates clouds the prospects for a safe vaccine. using antibodies from sars patients, we identified and characterized sars-cov b-cell peptide epitopes with disparate functions. in rhesus macaques, the spike glycoprotein peptides s471-503, ... | 2016 | 27627203 |
| immunodominant sars coronavirus epitopes in humans elicited both enhancing and neutralizing effects on infection in non-human primates. | severe acute respiratory syndrome (sars) is caused by a coronavirus (sars-cov) and has the potential to threaten global public health and socioeconomic stability. evidence of antibody-dependent enhancement (ade) of sars-cov infection in vitro and in non-human primates clouds the prospects for a safe vaccine. using antibodies from sars patients, we identified and characterized sars-cov b-cell peptide epitopes with disparate functions. in rhesus macaques, the spike glycoprotein peptides s471-503, ... | 2016 | 27627203 |
| antibody-dependent enhancement of sars coronavirus infection and its role in the pathogenesis of sars. | | 2016 | 27390007 |
| sars coronavirus fusion peptide-derived sequence suppresses collagen-induced arthritis in dba/1j mice. | during the co-evolution of viruses and their hosts, the viruses have evolved numerous strategies to counter and evade host antiviral immune responses in order to establish a successful infection, replicate and persist in the host. recently, based on our model of immune signaling, the signaling chain homooligomerization (school) model, we suggested specific molecular mechanisms used by different viruses such as severe acute respiratory syndrome coronavirus (sars-cov) to modulate the host immune r ... | 2016 | 27349522 |
| recognition of lys48-linked di-ubiquitin and deubiquitinating activities of the sars coronavirus papain-like protease. | deubiquitinating enzymes (dubs) recognize and cleave linkage-specific polyubiquitin (polyub) chains, but mechanisms underlying specificity remain elusive in many cases. the severe acute respiratory syndrome (sars) coronavirus papain-like protease (plpro) is a dub that cleaves isg15, a two-domain ub-like protein, and lys48-linked polyub chains, releasing diub(lys48) products. to elucidate this specificity, we report the 2.85 å crystal structure of sars plpro bound to a diub(lys48) activity-based ... | 2016 | 27203180 |
| sars coronavirus papain-like protease inhibits the tlr7 signaling pathway through removing lys63-linked polyubiquitination of traf3 and traf6. | severe acute respiratory syndrome coronavirus (sars-cov) papain-like protease (plpro) reportedly inhibits the production of type i interferons (ifns) and pro-inflammatory cytokines in toll-like receptor 3 (tlr3) and retinoic acid-inducible gene 1 (rig-i) pathways. the study investigated the inhibitory effect and its antagonistic mechanism of sars-cov plpro on tlr7-mediated cytokine production. tlr7 agonist (imiquimod (imq)) concentration-dependently induced activation of isre-, nf-κb- and ap-1-l ... | 2016 | 27164085 |
| coexistence of multiple coronaviruses in several bat colonies in an abandoned mineshaft. | since the 2002-2003 severe acute respiratory syndrome (sars) outbreak prompted a search for the natural reservoir of the sars coronavirus, numerous alpha- and betacoronaviruses have been discovered in bats around the world. bats are likely the natural reservoir of alpha- and betacoronaviruses, and due to the rich diversity and global distribution of bats, the number of bat coronaviruses will likely increase. we conducted a surveillance of coronaviruses in bats in an abandoned mineshaft in mojian ... | 2016 | 26920708 |
| coexistence of multiple coronaviruses in several bat colonies in an abandoned mineshaft. | since the 2002-2003 severe acute respiratory syndrome (sars) outbreak prompted a search for the natural reservoir of the sars coronavirus, numerous alpha- and betacoronaviruses have been discovered in bats around the world. bats are likely the natural reservoir of alpha- and betacoronaviruses, and due to the rich diversity and global distribution of bats, the number of bat coronaviruses will likely increase. we conducted a surveillance of coronaviruses in bats in an abandoned mineshaft in mojian ... | 2016 | 26920708 |
| antigen production in plant to tackle infectious diseases flare up: the case of sars. | severe acute respiratory syndrome (sars) is a dangerous infection with pandemic potential. it emerged in 2002 and its aetiological agent, the sars coronavirus (sars-cov), crossed the species barrier to infect humans, showing high morbidity and mortality rates. no vaccines are currently licensed for sars-cov and important efforts have been performed during the first outbreak to develop diagnostic tools. here we demonstrate the transient expression in nicotiana benthamiana of two important antigen ... | 2016 | 26904039 |
| design and synthesis of a series of serine derivatives as small molecule inhibitors of the sars coronavirus 3cl protease. | synthesis of serine derivatives having the essential functional groups for the inhibitor of sars 3cl protease and evaluation of their inhibitory activities using sars 3cl r188i mutant protease are described. the lead compounds, functionalized serine derivatives, were designed based on the tetrapeptide aldehyde and bai's cinnamoly inhibitor, and additionally performed with simulation on gold softwear. structure activity relationship studies of the candidate compounds were given reasonable inhibit ... | 2016 | 26879854 |
| conformational flexibility of a short loop near the active site of the sars-3clpro is essential to maintain catalytic activity. | the sars 3c-like proteinase (sars-3clpro), which is the main proteinase of the sars coronavirus, is essential to the virus life cycle. this enzyme has been shown to be active as a dimer in which only one protomer is active. however, it remains unknown how the dimer structure maintains an active monomer conformation. it has been observed that the ser139-leu141 loop forms a short 3(10)-helix that disrupts the catalytic machinery in the inactive monomer structure. we have tried to disrupt this heli ... | 2016 | 26879383 |
| sars-cov and ifn: too little, too late. | dysregulated type i interferon (ifn-i) expression can lead to severe pathology and disease. in this issue of cell host & microbe, channappanavar et al. (2016) use a sars-coronavirus animal model to describe how rapid and robust virus replication with delayed ifn-i can lead to lung immunopathology, with fatal outcomes. | 2016 | 26867172 |
| spatiotemporal interplay of severe acute respiratory syndrome coronavirus and respiratory mucosal cells drives viral dissemination in rhesus macaques. | innate immune responses have a critical role in the control of early virus replication and dissemination. it remains unknown, however, how severe acute respiratory syndrome coronavirus (sars-cov) evades respiratory innate immunity to establish a systemic infection. here we show in chinese macaques that sars-cov traversed the mucosa through the respiratory tract within 2 days, resulting in extensive mucosal infiltration by t cells, mac387(+), and cd163(+) monocytes/macrophages followed by limited ... | 2016 | 26647718 |
| reconstitution of the receptor-binding motif of the sars coronavirus. | the severe acute respiratory syndrome (sars) coronavirus (cov) identified in 2003 has infected ∼8000 people worldwide, killing nearly 10% of them. the infection of target cells by the sars cov is mediated through the interaction of the viral spike (s) protein (1255 amino acids) and its cellular receptor, angiotensin-converting enzyme 2 (ace2). the sars cov receptor-binding domain (amino acids n318-t509 of s protein) harbors an extended excursion along its periphery that contacts ace2 and is desi ... | 2015 | 26487711 |
| orf8-related genetic evidence for chinese horseshoe bats as the source of human severe acute respiratory syndrome coronavirus. | several lineage b betacoronaviruses termed severe acute respiratory syndrome (sars)-like covs (sl-covs) were identified from rhinolophus bats in china. these viruses are characterized by a set of unique accessory open reading frames (orfs) that are located between the m and n genes. among unique accessory orfs, orf8 is most hypervariable. in this study, the orf8s of all sl-covs were classified into 3 types, and, for the first time, it was found that very few sl-covs from rhinolophus sinicus have ... | 2016 | 26433221 |
| identification of a novel small molecule inhibitor against sars coronavirus helicase. | a new chemical inhibitor against severe acute respiratory syndrome (sars) coronavirus helicase, 7-ethyl-8-mercapto-3-methyl-3,7-dihydro-1h-purine-2,6-dione, was identified. we investigated the inhibitory effect of the compound by conducting colorimetry-based atp hydrolysis assay and fluorescence resonance energy transfer-based double-stranded dna unwinding assay. the compound suppressed both atp hydrolysis and double-stranded dna unwinding activities of helicase with ic50 values of 8.66 ± 0.26 μ ... | 2015 | 26387819 |
| use of isotope-edited ftir to derive a backbone structure of a transmembrane protein. | solving structures of membrane proteins has always been a formidable challenge, yet even upon success, the results are normally obtained in a mimetic environment that can be substantially different from a biological membrane. herein, we use noninvasive isotope-edited ftir spectroscopy to derive a structural model for the sars coronavirus e protein transmembrane domain in lipid bilayers. molecular-dynamics-based structural refinement, incorporating the ir-derived orientational restraints points t ... | 2014 | 26277945 |
| severe acute respiratory syndrome (sars) coronavirus orf8 protein is acquired from sars-related coronavirus from greater horseshoe bats through recombination. | despite the identification of horseshoe bats as the reservoir of severe acute respiratory syndrome (sars)-related coronaviruses (sarsr-covs), the origin of sars-cov orf8, which contains the 29-nucleotide signature deletion among human strains, remains obscure. although two sars-related rhinolophus sinicus bat covs (sarsr-rs-batcovs) previously detected in chinese horseshoe bats (rhinolophus sinicus) in yunnan, rsshc014 and rs3367, possessed 95% genome identities to human and civet sarsr-covs, th ... | 2015 | 26269185 |
| severe acute respiratory syndrome (sars) coronavirus orf8 protein is acquired from sars-related coronavirus from greater horseshoe bats through recombination. | despite the identification of horseshoe bats as the reservoir of severe acute respiratory syndrome (sars)-related coronaviruses (sarsr-covs), the origin of sars-cov orf8, which contains the 29-nucleotide signature deletion among human strains, remains obscure. although two sars-related rhinolophus sinicus bat covs (sarsr-rs-batcovs) previously detected in chinese horseshoe bats (rhinolophus sinicus) in yunnan, rsshc014 and rs3367, possessed 95% genome identities to human and civet sarsr-covs, th ... | 2015 | 26269185 |
| this could be the start of something big-20 years since the identification of bats as the natural host of hendra virus. | hendra virus was first described in 1994 in australia, causally associated with a cluster of fatal equine and human cases at a thoroughbred racing stable in the brisbane suburb of hendra. this year marks the twentieth anniversary of the identification of pteropid bats (flying-foxes) as the natural host of the virus, and it is timely to reflect on a pivotal meeting of an eclectic group of scientists in that process. they included animal and public health experts, environmental scientists, veterin ... | 2015 | 28616459 |
| structural basis and functional analysis of the sars coronavirus nsp14-nsp10 complex. | nonstructural protein 14 (nsp14) of coronaviruses (cov) is important for viral replication and transcription. the n-terminal exoribonuclease (exon) domain plays a proofreading role for prevention of lethal mutagenesis, and the c-terminal domain functions as a (guanine-n7) methyl transferase (n7-mtase) for mrna capping. the molecular basis of both these functions is unknown. here, we describe crystal structures of severe acute respiratory syndrome (sars)-cov nsp14 in complex with its activator no ... | 2015 | 26159422 |
| a g-quadruplex-binding macrodomain within the "sars-unique domain" is essential for the activity of the sars-coronavirus replication-transcription complex. | the multi-domain non-structural protein 3 of sars-coronavirus is a component of the viral replication/transcription complex (rtc). among other domains, it contains three sequentially arranged macrodomains: the x domain and subdomains sud-n as well as sud-m within the "sars-unique domain". the x domain was proposed to be an adp-ribose-1"-phosphatase or a poly(adp-ribose)-binding protein, whereas sud-nm binds oligo(g)-nucleotides capable of forming g-quadruplexes. here, we describe the application ... | 2015 | 26149721 |
| the sars-coronavirus papain-like protease: structure, function and inhibition by designed antiviral compounds. | over 10 years have passed since the deadly human coronavirus that causes severe acute respiratory syndrome (sars-cov) emerged from the guangdong province of china. despite the fact that the sars-cov pandemic infected over 8500 individuals, claimed over 800 lives and cost billions of dollars in economic loss worldwide, there still are no clinically approved antiviral drugs, vaccines or monoclonal antibody therapies to treat sars-cov infections. the recent emergence of the deadly human coronavirus ... | 2015 | 25554382 |
| the sars coronavirus papain like protease can inhibit irf3 at a post activation step that requires deubiquitination activity. | the outcome of a viral infection is regulated by complex interactions of viral and host factors. sars coronavirus (sars-cov) engages and regulates several innate immune response pathways during infection. we have previously shown that the sars-cov papain-like protease (plpro) inhibits type i interferon (ifn) by inhibiting irf3 phosphorylation thereby blocking downstream interferon induction. this finding prompted us to identify other potential mechanisms of inhibition of plpro on ifn induction. | 2014 | 25481026 |
| acquisition of new protein domains by coronaviruses: analysis of overlapping genes coding for proteins n and 9b in sars coronavirus. | acquisition of new proteins by viruses usually occurs through horizontal gene transfer or through gene duplication, but another, less common mechanism is the usage of completely or partially overlapping reading frames. a case of acquisition of a completely new protein through introduction of a start codon in an alternative reading frame is the protein encoded by open reading frame (orf) 9b of sars coronavirus. this gene completely overlaps with the nucleocapsid (n) gene (orf9a). our findings ind ... | 2015 | 25410051 |
| the sars-coronavirus membrane protein induces apoptosis via interfering with pdk1-pkb/akt signalling. | a number of viral gene products are capable of inducing apoptosis by interfering with various cellular signalling cascades. we previously reported the pro-apoptotic property of the sars-cov (severe acute respiratory syndrome coronavirus) m (membrane)-protein and a down-regulation of the phosphorylation level of the cell-survival protein pkb (protein kinase b)/akt in cells expressing m-protein. we also showed that overexpression of pdk1 (3-phosphoinositide-dependent protein kinase 1), the immedia ... | 2014 | 25271362 |
| substrate specificity and rational design of peptidomimetic inhibitors for sars coronavirus main protease. | | 2014 | 25224113 |
| sars-coronavirus open reading frame-9b suppresses innate immunity by targeting mitochondria and the mavs/traf3/traf6 signalosome. | coronaviruses (cov) have recently emerged as potentially serious pathogens that can cause significant human morbidity and death. the severe acute respiratory syndrome (sars)-cov was identified as the etiologic agent of the 2002-2003 international sars outbreak. yet, how sars evades innate immune responses to cause human disease remains poorly understood. in this study, we show that a protein encoded by sars-cov designated as open reading frame-9b (orf-9b) localizes to mitochondria and causes mit ... | 2014 | 25135833 |
| [new coronavirus infection: new challenges, new legacies]. | a new highly pathogenic human coronavirus has emerged. its natural history and its determinants are still under investigation. it lacks a publication to examine all the cases identified worldwide. therefore, the objective of this paper is to describe the cases and deaths caused by the new coronavirus. | 2017 | 25078748 |
| substitution at aspartic acid 1128 in the sars coronavirus spike glycoprotein mediates escape from a s2 domain-targeting neutralizing monoclonal antibody. | the severe acute respiratory syndrome coronavirus (sars-cov) is the etiological agent for the infectious disease, sars, which first emerged 10 years ago. sars-cov is a zoonotic virus that has crossed the species barriers to infect humans. bats, which harbour a diverse pool of sars-like covs (sl-covs), are believed to be the natural reservoir. the sars-cov surface spike (s) protein is a major antigenic determinant in eliciting neutralizing antibody production during sars-cov infection. in our pre ... | 2014 | 25019613 |
| accessory proteins of sars-cov and other coronaviruses. | the huge rna genome of sars coronavirus comprises a number of open reading frames that code for a total of eight accessory proteins. although none of these are essential for virus replication, some appear to have a role in virus pathogenesis. notably, some sars-cov accessory proteins have been shown to modulate the interferon signaling pathways and the production of pro-inflammatory cytokines. the structural information on these proteins is also limited, with only two (p7a and p9b) having their ... | 2014 | 24995382 |
| sars coronavirus without reservoir originated from an unnatural evolution, experienced the reverse evolution, and finally disappeared in the world. | | 2014 | 24985597 |
| development of a single nucleotide polymorphism dna microarray for the detection and genotyping of the sars coronavirus. | severe acute respiratory syndrome (sars), a disease that spread widely in the world during late 2002 to 2004, severely threatened public health. although there have been no reported infections since 2004, the extremely pathogenic sars coronavirus (sars-cov), as the causative agent of sars, has recently been identified in animals, showing the potential for the re-emergence of this disease. previous studies showed that 27 single nucleotide polymorphism (snp) mutations among the spike (s) gene of t ... | 2014 | 24950883 |
| the yxxφ motif within the severe acute respiratory syndrome coronavirus (sars-cov) 3a protein is crucial for its intracellular transport. | the sars coronavirus (sars-cov) 3a protein functions as an ion channel, induces apoptosis and is important for viral pathogenesis. it is expressed on the cell surface and contains a tyrosine-based sorting motif and a di-acidic motif, which may be crucial for its intracellular trafficking. however the role of these motifs is not fully understood in the case of 3a protein. | 2014 | 24762043 |
| phagocytic cells contribute to the antibody-mediated elimination of pulmonary-infected sars coronavirus. | while the 2002-2003 outbreak of severe acute respiratory syndrome (sars) resulted in 774 deaths, patients who were affected with mild pulmonary symptoms successfully recovered. the objective of the present work was to identify, using sars coronavirus (sars-cov) mouse infection models, immune factors responsible for clearing of the virus. the elimination of pulmonary sars-cov infection required the activation of b cells by cd4(+) t cells. furthermore, passive immunization (post-infection) with ho ... | 2014 | 24725942 |
| outcomes of sars survivors in china: not only physical and psychiatric co-morbidities. | the year 2013 marks the 10th anniversary of the outbreak of the severe acute respiratory syndrome (sars). we present a comprehensive introduction to the current situation of surviving sars victims in china where the disease originated and spread across the world 10 years ago. | 2014 | 24676486 |
| multi-organ lesions in suckling mice infected with sars-associated mammalian reovirus linked with apoptosis induced by viral proteins μ1 and σ1. | we reported the isolation and characterization of a novel mammalian reassortant reovirus byd1 that may have played an accomplice role with sars-coronavirus during the 2003 sars pandemic. the pathogenic mechanism of this novel reovirus is unknown. reovirus pathogenicity has been associated with virus-induced apoptosis in cultured cells and in vivo. the reovirus outer capsid protein μ1 is recognized as the primary determinant of reovirus-induced apoptosis. here, we investigated the apoptosis induc ... | 2014 | 24664247 |
| how change of public transportation usage reveals fear of the sars virus in a city. | the outbreaks of the severe acute respiratory syndrome (sars) epidemic in 2003 resulted in unprecedented impacts on people's daily life. one of the most significant impacts to people is the fear of contacting the sars virus while engaging daily routine activity. here we use data from daily underground ridership in taipei city and daily reported new sars cases in taiwan to model the dynamics of the public fear of the sars virus during the wax and wane of the sars period. we found that for each re ... | 2014 | 24647278 |
| severe acute respiratory syndrome-coronavirus infection in aged nonhuman primates is associated with modulated pulmonary and systemic immune responses. | many respiratory viruses disproportionately impact the elderly. likewise, advanced age correlated with more adverse disease outcomes following severe acute respiratory syndrome coronavirus (sars-cov) infection in humans. we used an aged african green monkey sars-cov infection model to better understand age-related mechanisms of increased susceptibility to viral respiratory infections. nonhuman primates are critical translational models for such research given their similarities to humans in immu ... | 2014 | 24642138 |
| sars coronavirus papain-like protease inhibits the type i interferon signaling pathway through interaction with the sting-traf3-tbk1 complex. | sars coronavirus (sars-cov) develops an antagonistic mechanism by which to evade the antiviral activities of interferon (ifn). previous studies suggested that sars-cov papain-like protease (plpro) inhibits activation of the irf3 pathway, which would normally elicit a robust ifn response, but the mechanism(s) used by sars plpro to inhibit activation of the irf3 pathway is not fully known. in this study, we uncovered a novel mechanism that may explain how sars plpro efficiently inhibits activation ... | 2014 | 24622840 |
| influence of hydrophobic and electrostatic residues on sars-coronavirus s2 protein stability: insights into mechanisms of general viral fusion and inhibitor design. | severe acute respiratory syndrome (sars) is an acute respiratory disease caused by the sars-coronavirus (sars-cov). sars-cov entry is facilitated by the spike protein (s), which consists of an n-terminal domain (s1) responsible for cellular attachment and a c-terminal domain (s2) that mediates viral and host cell membrane fusion. the sars-cov s2 is a potential drug target, as peptidomimetics against s2 act as potent fusion inhibitors. in this study, site-directed mutagenesis and thermal stabilit ... | 2014 | 24519901 |
| [bats, viruses and humans: coronaviruses on the rise?]. | the outbreak of the sars coronavirus in 2002/2003 and the recent disease cases with a new human coronavirus (originally designated emc-cov, recently renamed mers-cov) have put the focus onto the virus family coronaviridae. both viruses appeared to have managed to jump over the species barrier from a bat reservoir to the human population. bats are considered to serve as a natural reservoir for coronaviruses infecting mammals. an important factor for crossing the species-barrier is the adaptation ... | 2014 | 24511826 |
| kaempferol derivatives as antiviral drugs against the 3a channel protein of coronavirus. | the protein coded by the open-reading-frame 3a of sars coronavirus has been demonstrated to form a cation-selective channel that may become expressed in the infected cell. the activity of the channel is involved in the mechanism of virus release. drugs that inhibit the ion channel can, therefore, inhibit virus release, and they could be a source for development of novel therapeutic antiviral agents. various drugs found in chinese herbs that are well known as anticancer agents also have an antivi ... | 2014 | 24458263 |
| anti-frameshifting ligand reduces the conformational plasticity of the sars virus pseudoknot. | programmed -1 ribosomal frameshifting (-1 prf) stimulated by mrna pseudoknots regulates gene expression in many viruses, making pseudoknots potential targets for anti-viral drugs. the mechanism by which pseudoknots trigger -1 prf, however, remains controversial, with several competing models. recent work showed that high -1 prf efficiency was linked to high pseudoknot conformational plasticity via the formation of alternate conformers. we tested whether pseudoknots bound with an anti-frameshifti ... | 2014 | 24446874 |
| the sars coronavirus nucleocapsid protein--forms and functions. | the nucleocapsid phosphoprotein of the severe acute respiratory syndrome coronavirus (sars-cov n protein) packages the viral genome into a helical ribonucleocapsid (rnp) and plays a fundamental role during viral self-assembly. it is a protein with multifarious activities. in this article we will review our current understanding of the n protein structure and its interaction with nucleic acid. highlights of the progresses include uncovering the modular organization, determining the structures of ... | 2014 | 24418573 |
| atlas of coronavirus replicase structure. | the international response to sars-cov has produced an outstanding number of protein structures in a very short time. this review summarizes the findings of functional and structural studies including those derived from cryoelectron microscopy, small angle x-ray scattering, nmr spectroscopy, and x-ray crystallography, and incorporates bioinformatics predictions where no structural data is available. structures that shed light on the function and biological roles of the proteins in viral replicat ... | 2014 | 24355834 |
| severe acute respiratory syndrome beyond amoy gardens: completing the incomplete legacy. | the temporal and spatial distributions of the 2003 severe acute respiratory syndrome (sars) outbreak in amoy gardens of hong kong was reexamined using all confirmed cases. the outbreak actually extended to nearby residential complexes. airborne spread was the most likely explanation, and the sars coronavirus could have spread over a distance of 200 m. | 2014 | 24319085 |
| sars-cov orf1b-encoded nonstructural proteins 12-16: replicative enzymes as antiviral targets. | the sars (severe acute respiratory syndrome) pandemic caused ten years ago by the sars-coronavirus (sars-cov) has stimulated a number of studies on the molecular biology of coronaviruses. this research has provided significant new insight into many mechanisms used by the coronavirus replication-transcription complex (rtc). the rtc directs and coordinates processes in order to replicate and transcribe the coronavirus genome, a single-stranded, positive-sense rna of outstanding length (∼27-32kilob ... | 2014 | 24269475 |
| respiratory virus detection: beyond influenza and rsv into emerging infectious diseases. | in the era of global travel, clinicians can no longer consider just influenza and respiratory synctial virus (rsv) and ignore other causes of presumptive viral respiratory tract infections. since the recognition of severe acute respiratory syndrome (sars) coronavirus in 2003, novel viruses seem to emerge more frequently. novel influenza strains, the novel coronavirus (mers-cov) identified last year in the middle east, other novel viruses, and increasing numbers of immunocompromised patients that ... | 2013 | 24261155 |
| severe acute respiratory syndrome (sars) coronavirus: possible re-emergence of the asian-global novel threat. | | 2013 | 24260834 |
| bats as animal reservoirs for the sars coronavirus: hypothesis proved after 10 years of virus hunting. | | 2013 | 24174406 |
| proteolytic activation of the sars-coronavirus spike protein: cutting enzymes at the cutting edge of antiviral research. | the severe acute respiratory syndrome (sars) pandemic revealed that zoonotic transmission of animal coronaviruses (cov) to humans poses a significant threat to public health and warrants surveillance and the development of countermeasures. the activity of host cell proteases, which cleave and activate the sars-cov spike (s) protein, is essential for viral infectivity and constitutes a target for intervention. however, the identities of the proteases involved have been unclear. pioneer studies id ... | 2013 | 24121034 |
| severe acute respiratory syndrome (sars): lessons learnt in hong kong. | many healthcare workers were infected while looking after the sars patients on the medical wards in 2003. the high infectivity of the sars coronavirus with peak viral load on day 10 of illness when patients were ill, overcrowding of the old medical wards with low air changes/hr (ach), and aerosol-generating procedures while resuscitating the patients were the major factors. procedures reported to present an increased risk of sars transmission include tracheal intubation, non-invasive ventilation ... | 2013 | 23977432 |
| ace2 - from the renin-angiotensin system to gut microbiota and malnutrition. | the renin-angiotensin system (ras) is a complex network that regulates blood pressure, electrolyte and fluid homeostasis, as well as the function of several organs. angiotensin-converting enzyme 2 (ace2) was identified as an enzyme that negatively regulates the ras by converting ang ii, the main bioactive molecule of the ras, to ang 1-7. thus, ace2 counteracts the role of angiotensin-converting enzyme (ace) which generates ang ii from ang i. ace and ace2 have been implicated in several pathologi ... | 2013 | 23962453 |