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evaluation of cotton rats as a model for severe acute respiratory syndrome.experimental studies were conducted to evaluate two species of cotton rats, sigmodon hispidus and sigmodon fulviventer, as a model for severe acute respiratory syndrome (sars). blood and turbinate wash samples, and lung tissue were collected from each animal at different time points after sars coronavirus (cov) infection for determining the growth curve of virus, if any, by the standard infectivity assay in vero e6 cells. in addition, sections of the lung, liver, spleen, and kidney were taken an ...200818447621
evaluation of cotton rats as a model for severe acute respiratory syndrome.experimental studies were conducted to evaluate two species of cotton rats, sigmodon hispidus and sigmodon fulviventer, as a model for severe acute respiratory syndrome (sars). blood and turbinate wash samples, and lung tissue were collected from each animal at different time points after sars coronavirus (cov) infection for determining the growth curve of virus, if any, by the standard infectivity assay in vero e6 cells. in addition, sections of the lung, liver, spleen, and kidney were taken an ...200818447621
what caused lymphopenia in sars and how reliable is the lymphokine status in glucocorticoid-treated patients?severe acute respiratory syndrome (sars) outbreak in 2002-03 caused morbidity in over 8000 individuals and mortality in 744 in 29 countries. lymphopenia along with neutrophilia was a feature of sars, as it is in respiratory syncytial virus (rsv) and ebola infections, to name a few. direct infestation of lymphocytes, neutrophils and macrophages by sars coronavirus (cov) has been debated as a cause of lymphopenia, but there is no convincing data. lymphopenia can be caused by glucocorticoids, and t ...200818448259
the nucleocapsid protein of severe acute respiratory syndrome coronavirus inhibits cell cytokinesis and proliferation by interacting with translation elongation factor 1alpha.severe acute respiratory syndrome coronavirus (sars-cov) is the etiological agent of sars, an emerging disease characterized by atypical pneumonia. using a yeast two-hybrid screen with the nucleocapsid (n) protein of sars-cov as a bait, the c terminus (amino acids 251 to 422) of the n protein was found to interact with human elongation factor 1-alpha (ef1alpha), an essential component of the translational machinery with an important role in cytokinesis, promoting the bundling of filamentous acti ...200818448518
severe acute respiratory syndrome coronavirus protein 6 accelerates murine hepatitis virus infections by more than one mechanism.the severe acute respiratory syndrome coronavirus (sars-cov) encodes numerous accessory proteins whose importance in the natural infection process is currently unclear. one of these accessory proteins is set apart by its function in the context of a related murine hepatitis virus (mhv) infection. sars-cov protein 6 increases mhv neurovirulence and accelerates mhv infection kinetics in tissue culture. protein 6 also blocks nuclear import of macromolecules from the cytoplasm, a process known to in ...200818448520
structural analysis of major species barriers between humans and palm civets for severe acute respiratory syndrome coronavirus infections.it is believed that a novel coronavirus, severe acute respiratory syndrome coronavirus (sars-cov), was passed from palm civets to humans and caused the epidemic of sars in 2002 to 2003. the major species barriers between humans and civets for sars-cov infections are the specific interactions between a defined receptor-binding domain (rbd) on a viral spike protein and its host receptor, angiotensin-converting enzyme 2 (ace2). in this study a chimeric ace2 bearing the critical n-terminal helix fro ...200818448527
the discovery of angiotensin-converting enzyme 2 and its role in acute lung injury in mice.during several months of 2002, severe acute respiratory syndrome (sars) caused by sars-coronavirus (sars-cov) spread rapidly from china throughout the world, causing more than 800 deaths due to the development of acute respiratory distress syndrome (ards), which is the severe form of acute lung injury (ali). interestingly, a novel homologue of angiotensin-converting enzyme, termed angiotensin-converting enzyme 2 (ace2), has been identified as a receptor for sars-cov. angiotensin-converting enzym ...200818448662
sirna silencing of angiotensin-converting enzyme 2 reduced severe acute respiratory syndrome-associated coronavirus replications in vero e6 cells.the outbreak of severe acute respiratory syndrome (sars) in 2002-2003 has had a significant impact worldwide. no effective prophylaxis or treatment for sars is available up to now. angiotensin-converting enzyme 2 (ace2) is the cellular receptor for sars-associated coronavirus (sars-cov). by expressing a u6 promoter-driven small interfering rna containing sequences homologous to part of ace2 mrna, we successfully silenced ace2 expression in vero e6 cells. by detecting negative strand sars-cov rna ...200818449585
sars-coronavirus replication/transcription complexes are membrane-protected and need a host factor for activity in vitro.sars-coronavirus (sars-cov) replication and transcription are mediated by a replication/transcription complex (rtc) of which virus-encoded, non-structural proteins (nsps) are the primary constituents. the 16 sars-cov nsps are produced by autoprocessing of two large precursor polyproteins. the rtc is believed to be associated with characteristic virus-induced double-membrane structures in the cytoplasm of sars-cov-infected cells. to investigate the link between these structures and viral rna synt ...200818451981
pathogenicity of severe acute respiratory coronavirus deletion mutants in hace-2 transgenic mice.recombinant severe acute respiratory virus (sars-cov) variants lacking the group specific genes 6, 7a, 7b, 8a, 8b and 9b (rsars-cov-delta[6-9b]), the structural gene e (rsars-cov-deltae), and a combination of both sets of genes (rsars-cov-delta[e,6-9b]) have been generated. all these viruses were rescued in monkey (vero e6) cells and were also infectious for human (huh-7, huh7.5.1 and caco-2) cell lines and for transgenic (tg) mice expressing the sars-cov receptor human angiotensin converting en ...200818452964
[human coronaviruses].coronaviruses are a large group of viruses and infect a lot of species of mammals and birds. five coronaviruses currently infect humans: hcovs 229e and oc43, identified in the 1960s, sars-cov identified in march 2003 during the sars epidemic, and the hcovs nl63 and hku1, identified in 2004 and 2005 respectively. the genome of the coronaviruses is a linear, non-segmented, positive-sense single-stranded rna molecule of approximately 30kb. the evolution of these viruses occurs through some features ...200918456429
molecular epidemiology of the coronavirus associated with severe acute respiratory syndrome: a review of data from the chinese university of hong kong.the epidemic of the severe acute respiratory syndrome (sars) has swept through the globe with more than 8000 reported probable cases. in hong kong, the hardest hit areas included our teaching hospital and the amoy gardens apartment complex. a novel coronavirus, sars-coronavirus (sars-cov), with a single-stranded plus sense rna genome, was promptly implicated as the causative agent and subsequently fulfilled koch's postulates. to aid the understanding of sars-cov, groups of investigators rapidly ...200418458710
the laboratory diagnosis of severe acute respiratory syndrome: emerging laboratory tests for an emerging pathogen.the 2003 pandemic of severe acute respiratory syndrome (sars) profiled the ability of modern diagnostic microbiology and molecular biology to identify, isolate and characterize, within weeks, a previously unknown viral infectious pathogen. the culprit, sars coronavirus (sars-cov), was detected in patient specimens by traditional cell culture using an unusual cell line for respiratory viruses, vero e6, and by reverse transcriptase polymerase chain reaction (rt-pcr) targeting the polymerase 1 b re ...200418458711
a live attenuated severe acute respiratory syndrome coronavirus is immunogenic and efficacious in golden syrian hamsters.the immunogenicity and protective efficacy of a live attenuated vaccine consisting of a recombinant severe acute respiratory syndrome (sars) coronavirus lacking the e gene (rsars-cov-deltae) were studied using hamsters. hamsters immunized with rsars-cov-deltae developed high serum-neutralizing antibody titers and were protected from replication of homologous (sars-cov urbani) and heterologous (gd03) sars-cov in the upper and lower respiratory tract. rsars-cov-deltae-immunized hamsters remained a ...200818463152
a live attenuated severe acute respiratory syndrome coronavirus is immunogenic and efficacious in golden syrian hamsters.the immunogenicity and protective efficacy of a live attenuated vaccine consisting of a recombinant severe acute respiratory syndrome (sars) coronavirus lacking the e gene (rsars-cov-deltae) were studied using hamsters. hamsters immunized with rsars-cov-deltae developed high serum-neutralizing antibody titers and were protected from replication of homologous (sars-cov urbani) and heterologous (gd03) sars-cov in the upper and lower respiratory tract. rsars-cov-deltae-immunized hamsters remained a ...200818463152
a novel strategy for analyzing rna-protein interactions by surface plasmon resonance biosensor.surface plasmon resonance (spr) biosensor is a promising technology for its various advantages including the real-time measurement of biomolecular interactions without labeling. a method of hybridizing rnas on the surface of the streptavidin-coated (sa) sensor chip to study rna-protein interactions was described in this paper. in our study, it has been shown that the nucleocapsid (n) protein of severe acute respiratory syndrome coronavirus (sars-cov) has a high binding affinity for the leader se ...200818465270
human line1 endonuclease domain as a putative target of sars-associated autoantibodies involved in the pathogenesis of severe acute respiratory syndrome.severe acute respiratory syndrome (sars) is a disease with a mortality of 9.56%. although sars is etiologically linked to a new coronavirus (sars-cov) and functional cell receptor has been identified, the pathogenesis of the virus infection is largely unclear.200818466680
mouse-passaged severe acute respiratory syndrome-associated coronavirus leads to lethal pulmonary edema and diffuse alveolar damage in adult but not young mice.advanced age is a risk factor of severe acute respiratory syndrome (sars) in humans. to understand its pathogenesis, we developed an animal model using balb/c mice and the mouse-passaged frankfurt 1 isolate of sars coronavirus (sars-cov). we examined the immune responses to sars-cov in both young and adult mice. sars-cov induced severe respiratory illness in all adult, but not young, mice on day 2 after inoculation with a mortality rate of 30 to 50%. moribund adult mice showed severe pulmonary e ...200818467696
combination of functionalized nanoparticles and polymerase chain reaction-based method for sars-cov gene detection.rapid and sensitive detection of sars associated coronavirus is critical for early diagnosis and control of severe acute respiratory syndrome. this study describes a method for the detection of sars associated coronavirus gene by the combination of functionalized nanoparticles and pcr-based assay. in this method, the target cdna of sars associated coronavirus was firstly captured and enriched from the mixture of target cdna and non-target cdna by the use of the functionalized silica coated super ...200818468073
[emerging viral infections in belgium and abroad].viral diseases are a moving world with epidemic upsurges, the disappearance of some infections and the temporary or definitive appearance of others. each year our country is stricken by flu epidemics, but at some points of time unexpected new flu viruses may cause a worldwide pandemic. presently a number of viral diseases have disappeared or are disappearing from our country, as smallpox, poliomyelitis, rabies, measles or rubella. many factors, some changing others more persistent, may explain t ...200818479078
immunomodulatory and anti-sars activities of houttuynia cordata.severe acute respiratory syndrome (sars) is a life-threatening form of pneumonia caused by sars coronavirus (sars-cov). from late 2002 to mid 2003, it infected more than 8000 people worldwide, of which a majority of cases were found in china. owing to the absence of definitive therapeutic western medicines, houttuynia cordata thunb. (saururaceae)(hc) was shortlisted by chinese scientists to tackle sars problem as it is conventionally used to treat pneumonia.200818479853
rapid discovery and optimization of therapeutic antibodies against emerging infectious diseases.using a comprehensive set of discovery and optimization tools, antibodies were produced with the ability to neutralize sars coronavirus (sars-cov) infection in vero e6 cells and in animal models. these anti-sars antibodies were discovered using a novel dna display method, which can identify new antibodies within days. once neutralizing antibodies were identified, a comprehensive and effective means of converting the mouse sequences to human frameworks was accomplished using hufr (human framework ...200818480090
structural and dynamic characterization of the interaction of the putative fusion peptide of the s2 sars-cov virus protein with lipid membranes.the sars coronavirus (sars-cov) envelope spike (s) glycoprotein, a class i viral fusion protein, is responsible for the fusion between the membranes of the virus and the target cell. in the present work, we report a study of the binding and interaction with model membranes of a peptide pertaining to the putative fusion domain of sars-cov, sars fp, as well as the structural changes that take place in both the phospholipid and the peptide molecules upon this interaction. from fluorescence and infr ...200818489147
modulation of tnf-alpha-converting enzyme by the spike protein of sars-cov and ace2 induces tnf-alpha production and facilitates viral entry.severe acute respiratory syndrome coronavirus (sars-cov) is a high-risk infectious pathogen. in the proposed model of respiratory failure, sars-cov down-regulates its receptor, angiotensin-converting enzyme 2 (ace2), but the mechanism involved is unknown. we found that the spike protein of sars-cov (sars-s) induced tnf-alpha-converting enzyme (tace)-dependent shedding of the ace2 ectodomain. the modulation of tace activity by sars-s depended on the cytoplasmic domain of ace2, because deletion mu ...200818490652
severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ace2.infection of humans with the severe acute respiratory syndrome coronavirus (sars-cov) results in substantial morbidity and mortality, with death resulting primarily from respiratory failure. while the lungs are the major site of infection, the brain is also infected in some patients. brain infection may result in long-term neurological sequelae, but little is known about the pathogenesis of sars-cov in this organ. we previously showed that the brain was a major target organ for infection in mice ...200818495771
predicting linear b-cell epitopes using string kernels.the identification and characterization of b-cell epitopes play an important role in vaccine design, immunodiagnostic tests, and antibody production. therefore, computational tools for reliably predicting linear b-cell epitopes are highly desirable. we evaluated support vector machine (svm) classifiers trained utilizing five different kernel methods using fivefold cross-validation on a homology-reduced data set of 701 linear b-cell epitopes, extracted from bcipep database, and 701 non-epitopes, ...200818496882
coronavirus antibodies in bat biologists. 200818507931
the role of programmed-1 ribosomal frameshifting in coronavirus propagation.coronaviruses have the potential to cause significant economic, agricultural and health problems. the severe acute respiratory syndrome (sars) associated coronavirus outbreak in late 2002, early 2003 called attention to the potential damage that coronaviruses could cause in the human population. the ensuing research has enlightened many to the molecular biology of coronaviruses. a programmed -1 ribosomal frameshift is required by coronaviruses for the production of the rna dependent rna polymera ...200818508552
[sars-cov infection and pregnancy].sars is a highly contagious infection, caused by new coronavirus sars-cov. immunopathological mechanisms responsible for the reaction to sars-cov infection have not yet been fully elucidated. cytokine profile of sars patients showed marked elevation of th1 cytokine, interferon gamma, inflammatory cytokines for at least 2 weeks after the onset of the disease. the clinical manifestation of sars in patients has been of varied nature. fever of more then 38 degrees c, lasting more then 24 hours, is t ...200818510050
a chimeric multi-epitope dna vaccine elicited specific antibody response against severe acute respiratory syndrome-associated coronavirus which attenuated the virulence of sars-cov in vitro.epitope-based vaccines designed to induce antibody responses specific for severe acute respiratory syndrome-associated coronavirus (sars-cov) are being developed as a means for increasing vaccine potency. in this study, we identified four b cell epitopes from the spike (s) and membrane (m) protein through bioinformatics analysis and constructed a multi-epitope dna vaccine. intramuscular immunization of mice with this vaccine was sufficient to induce specific prime as well as a long-term memory h ...200818533276
structure of a sars coronavirus-derived peptide bound to the human major histocompatibility complex class i molecule hla-b*1501.the human leukocyte antigen (hla) class i system comprises a highly polymorphic set of molecules that specifically bind and present peptides to cytotoxic t cells. hla-b*1501 is a prototypical member of the hla-b62 supertype and only two peptide-hla-b*1501 structures have been determined. here, the crystal structure of hla-b*1501 in complex with a sars coronavirus-derived nonapeptide (vqqessfvm) has been determined at high resolution (1.87 a). the peptide is deeply anchored in the b and f pockets ...200818540051
characterization of the prefusion and transition states of severe acute respiratory syndrome coronavirus s2-hr2.the envelope glycoproteins of the class i family, which include human immunodeficiency virus (hiv), influenza, and severe acute respiratory syndrome coronavirus (sars-cov), mediate viral entry by first binding to their cellular receptors and subsequently inducing fusion of the viral and cellular membranes. in the case of sars-cov, heptad repeat domains of the envelope glycoprotein, termed s2-hr1 and s2-hr2, are thought to undergo structural changes from a prefusion state, in which s2-hr1 and s2- ...200818540634
endocytosis of the receptor-binding domain of sars-cov spike protein together with virus receptor ace2.cell entry of severe acute respiratory syndrome coronavirus (sars-cov) is mediated by the viral spike (s) protein. amino acids 319-510 on the s protein have been mapped as the receptor-binding domain (rbd), which mediates binding to the sars-cov receptor angiotensin converting enzyme 2 (ace2) on sars-cov susceptible cells. in this study, we expressed a fusion protein containing the human codon-optimized rbd of the sars-cov spike protein linked to the fc portion of human igg1 (named rbd-fc) in he ...200818554741
a structural view of the inactivation of the sars coronavirus main proteinase by benzotriazole esters.the main proteinase (m(pro)) of the severe acute respiratory syndrome (sars) coronavirus is a principal target for the design of anticoronaviral compounds. benzotriazole esters have been reported as potent nonpeptidic inhibitors of the enzyme, but their exact mechanism of action remains unclear. here we present crystal structures of sars-cov m(pro), the active-site cysteine of which has been acylated by benzotriazole esters that act as suicide inhibitors. in one of the structures, the thioester ...200818559270
potent in vitro activity of the albumin fusion type 1 interferons (albumin-interferon-alpha and albumin-interferon-beta) against rna viral agents of bioterrorism and the severe acute respiratory syndrome (sars) virus.the type 1 interferons (inf-alpha and inf-beta) are potent antiviral agents. albumin-inf-alpha and albumin-inf-beta are novel recombinant proteins consisting of ifn-alpha or ifn-beta genetically fused to human albumin.200818560223
solution structure of the c-terminal dimerization domain of sars coronavirus nucleocapsid protein solved by the sail-nmr method.the c-terminal domain (ctd) of the severe acute respiratory syndrome coronavirus (sars-cov) nucleocapsid protein (np) contains a potential rna-binding region in its n-terminal portion and also serves as a dimerization domain by forming a homodimer with a molecular mass of 28 kda. so far, the structure determination of the sars-cov np ctd in solution has been impeded by the poor quality of nmr spectra, especially for aromatic resonances. we have recently developed the stereo-array isotope labelin ...200818561946
cathepsin l functionally cleaves the severe acute respiratory syndrome coronavirus class i fusion protein upstream of rather than adjacent to the fusion peptide.unlike other class i viral fusion proteins, spike proteins on severe acute respiratory syndrome coronavirus virions are uncleaved. as we and others have demonstrated, infection by this virus depends on cathepsin proteases present in endosomal compartments of the target cell, suggesting that the spike protein acquires its fusion competence by cleavage during cell entry rather than during virion biogenesis. here we demonstrate that cathepsin l indeed activates the membrane fusion function of the s ...200818562523
peptides from the sars-associated coronavirus as tags for protein expression and purification.protein tagging with a peptide is a commonly used technique to facilitate protein detection and to carry out protein purification. flexibility with respect to the peptide tag is essential since no single tag suites all purposes. this report describes the usage of two short peptides from the sars-associated coronavirus nucleocapsid (sars-n) protein as protein tags. plasmids for the generation of tagged proteins were generated by ligating synthetic oligonucleotides for the peptide-coding regions d ...200818565762
the management of coronavirus infections with particular reference to sars.the human coronaviruses (hcov) oc43 and 229e are common causes of upper respiratory tract infections. severe diseases were rare, however, until the emergence of the severe acute respiratory syndrome (sars)-cov in 2003. since then, other novel cov (nl63 and hku1) have been described, and they have caused respiratory infections worldwide. potentially exposed laboratory workers or animal handlers with rapidly progressive pneumonia not responding to standard antibacterial coverage must be isolated w ...200818565970
qm/qm studies for michael reaction in coronavirus main protease (3cl pro).severe acute respiratory syndrome (sars) is an illness caused by a novel corona virus wherein the main proteinase called 3cl(pro) has been established as a target for drug design. the mechanism of action involves nucleophilic attack by cys145 present in the active site on the carbonyl carbon of the scissile amide bond of the substrate and the intermediate product is stabilized by hydrogen bonds with the residues of the oxyanion hole. based on the x-ray structure of 3cl(pro) co-crystallized with ...200818567519
pathways of cross-species transmission of synthetically reconstructed zoonotic severe acute respiratory syndrome coronavirus.zoonotic severe acute respiratory syndrome coronavirus (sars-cov) likely evolved to infect humans by a series of transmission events between humans and animals in markets in china. virus sequence data suggest that the palm civet served as an amplification host in which civet and human interaction fostered the evolution of the epidemic sars urbani strain. the prototypic civet strain of sars-cov, sz16, was isolated from a palm civet but has not been successfully cultured in vitro. to propagate a c ...200818579604
high-throughput assay using a gfp-expressing replicon for sars-cov drug discovery.the causative agent of severe acute respiratory syndrome (sars) has been identified as a novel coronavirus, sars-cov. the development of rapid screening assays is essential for antiviral drug discovery. by using a cell line expressing a sars-cov subgenomic replicon, we developed a high-throughput assay and used it to screen small molecule compounds for inhibitors of sars-cov replication in the absence of live virus. the assay system involves minimal manipulation after assay set-up, facilitates a ...200818584889
pathology of experimental sars coronavirus infection in cats and ferrets.the pathology of severe acute respiratory syndrome-coronavirus (sars-cov) infection in cats and ferrets is poorly described, and the distribution of angiotensin-converting enzyme 2 (ace2), a receptor for sars-cov, in the respiratory tracts of these species is unknown. we observed sars-cov antigen expression and lesions in the respiratory tracts of 4 cats and 4 ferrets at 4 days postinoculation and ace2 expression in the respiratory tracts of 3 cats and 3 ferrets without infection. all infected c ...200818587105
wse, a new sequence distance measure based on word frequencies.in this article, we present a new distance metric, the weighted sequence entropy (wse), based on the short word composition of biological sequences. as a revision of the classical relative entropy (re), our metric (1) works equivalently with re in the case of small k, (2) avoids the degeneracy when some word types are absent in one sequence but not in the other. experiments on 25 viruses including sars-covs show that our method and re give exactly the same phylogenetic tree when word length k <o ...200818590747
severe acute respiratory syndrome coronavirus nucleocapsid protein confers ability to efficiently produce virus-like particles when substituted for the human immunodeficiency virus nucleocapsid domain.we replaced the hiv-1 nucleocapsid (nc) domain with different n-coding sequences to test sars-cov nucleocapsid (n) self-interaction capacity, and determined the capabilities of each chimera to direct virus-like particle (vlp) assembly. analysis results indicate that the replacement of nc with the carboxyl-terminal half of the sars-cov n resulted in the production of wild type (wt)-level virus-like particles (vlps) with the density of a wt hiv-1 particle. when co-expressed with sars-cov n, chimer ...200818592403
dc-sign mediates avian h5n1 influenza virus infection in cis and in trans.dc-sign, a c-type lectin receptor expressed in dendritic cells (dcs), has been identified as a receptor for human immunodeficiency virus type 1, hepatitis c virus, ebola virus, cytomegalovirus, dengue virus, and the sars coronavirus. we used h5n1 pseudotyped and reverse-genetics (rg) virus particles to study their ability to bind with dc-sign. electronic microscopy and functional assay results indicate that pseudotyped viruses containing both ha and na proteins express hemagglutination and are c ...200818593570
a single amino acid substitution in the s1 and s2 spike protein domains determines the neutralization escape phenotype of sars-cov.in response to sars-cov infection, neutralizing antibodies are generated against the spike (s) protein. determination of the active regions that allow viral escape from neutralization would enable the use of these antibodies for future passive immunotherapy. we immunized mice with uv-inactivated sars-cov to generate three anti-s monoclonal antibodies, and established several neutralization escape mutants with s protein. we identified several amino acid substitutions, including y442f and v601g in ...200818606245
development of broad-spectrum halomethyl ketone inhibitors against coronavirus main protease 3cl(pro).coronaviruses comprise a large group of rna viruses with diverse host specificity. the emergence of highly pathogenic strains like the sars coronavirus (sars-cov), and the discovery of two new coronaviruses, nl-63 and hku1, corroborates the high rate of mutation and recombination that have enabled them to cross species barriers and infect novel hosts. for that reason, the development of broad-spectrum antivirals that are effective against several members of this family is highly desirable. this ...200818611220
a second sars-cov s2 glycoprotein internal membrane-active peptide. biophysical characterization and membrane interaction.the severe acute respiratory syndrome coronavirus (sars-cov) envelope spike (s) glycoprotein, a class i viral fusion protein, is responsible for the fusion between the membranes of the virus and the target cell. the s2 domain of protein s has been suggested to have two fusion peptides, one located at its n-terminus, downstream of the furin cleavage, and another, more internal, located immediately upstream of the hr1. therefore, we have carried out a study of the binding and interaction with mode ...200818616295
construction of a non-infectious sars coronavirus replicon for application in drug screening and analysis of viral protein function.severe acute respiratory syndrome virus (sars-cov) was the causative agent of the sars outbreaks in 2002-2003. a safer in vitro system is desirable for conducting research on sars-cov and to screen for antiviral drugs against the virus. based on the infectious cdna clone of rsars-cov-deltae, in which the e gene has been deleted, a safe non-infectious replicon was constructed by replacing the s gene with the enhanced green fluorescent protein (egfp) gene. successful replication was achieved as ev ...200818619943
a rapid point of care immunoswab assay for sars-cov detection.the emergence of severe acute respiratory syndrome (sars) resulted in several outbreaks worldwide. early tests for diagnosis were not always conclusive in identifying a sars suspected patient. nucleocapsid protein (np) is the most predominant virus derived structural protein which is shed in high amounts in serum and nasopharyngeal aspirate during the first week of infection. as part of such efforts, a simple, easy to use immunoswab method was developed by generating a panel of monoclonal antibo ...200818620761
virus-like particles of sars-like coronavirus formed by membrane proteins from different origins demonstrate stimulating activity in human dendritic cells.the pathogenesis of sars coronavirus (cov) remains poorly understood. in the current study, two recombinant baculovirus were generated to express the spike (s) protein of sars-like coronavirus (sl-cov) isolated from bats (vacbs) and the envelope (e) and membrane (m) proteins of sars-cov, respectively. co-infection of insect cells with these two recombinant baculoviruses led to self-assembly of virus-like particles (bvlps) as demonstrated by electron microscopy. incorporation of s protein of vacb ...200818628832
phosphorylation of the arginine/serine dipeptide-rich motif of the severe acute respiratory syndrome coronavirus nucleocapsid protein modulates its multimerization, translation inhibitory activity and cellular localization.coronavirus nucleocapsid protein is abundant in infected cells and participates in viral rna replication and transcription. the central domain of the nucleocapsid protein contains several arginine/serine (rs) dipeptides, the biological significance of which has not been well investigated. in the present study, we demonstrate that the severe acute respiratory syndrome coronavirus nucleocapsid protein is phosphorylated primarily within the rs-rich region in cells and by sr protein kinase 1 in vitr ...200818631359
the transmembrane domain of the severe acute respiratory syndrome coronavirus orf7b protein is necessary and sufficient for its retention in the golgi complex.the severe acute respiratory syndrome coronavirus (sars-cov) orf7b (also called 7b) protein is an integral membrane protein that is translated from a bicistronic open reading frame encoded within subgenomic rna 7. when expressed independently or during virus infection, orf7b accumulates in the golgi compartment, colocalizing with both cis- and trans-golgi markers. to identify the domains of this protein that are responsible for golgi localization, we have generated a set of mutant proteins and a ...200818632859
genomic analysis reveals age-dependent innate immune responses to severe acute respiratory syndrome coronavirus.the relationship between immunosenescence and the host response to virus infection is poorly understood at the molecular level. two different patterns of pulmonary host responses to virus were observed when gene expression profiles from severe acute respiratory syndrome coronavirus (sars-cov)-infected young mice that show minimal disease were compared to those from sars-cov-infected aged mice that develop pneumonitis. in young mice, genes related to cellular development, cell growth, and cell cy ...200818632870
severe acute respiratory syndrome coronavirus 3a protein activates the mitochondrial death pathway through p38 map kinase activation.the molecular mechanisms governing severe acute respiratory syndrome coronavirus-induced pathology are not fully understood. virus infection and some individual viral proteins, including the 3a protein, induce apoptosis. however, the cellular targets leading to 3a protein-mediated apoptosis have not been fully characterized. this study showed that the 3a protein modulates the mitochondrial death pathway in two possible ways. activation of caspase-8 through extrinsic signal(s) caused bid activati ...200818632968
structural flexibility of the pentameric sars coronavirus envelope protein ion channel.coronaviruses contain a small envelope membrane protein with cation-selective ion channel activity mediated by its transmembrane domain (etm). in a computational study, we proposed that ion channel activity can be explained by either of two similar etm homopentameric transmembrane alpha-helical bundles, related by a approximately 50 degrees rotation of the helices. later, we tested this prediction, using site-specific infrared dichroism of a lysine-flanked isotopically labeled etm peptide from t ...200818658207
bench-to-bedside review: rare and common viral infections in the intensive care unit--linking pathophysiology to clinical presentation.viral infections are common causes of respiratory tract disease in the outpatient setting but much less common in the intensive care unit. however, a finite number of viral agents cause respiratory tract disease in the intensive care unit. some viruses, such as influenza, respiratory syncytial virus (rsv), cytomegalovirus (cmv), and varicella-zoster virus (vzv), are relatively common. others, such as adenovirus, severe acute respiratory syndrome (sars)-coronavirus, hantavirus, and the viral hemo ...200818671826
genomic analysis and geographic visualization of h5n1 and sars-cov.emerging infectious diseases and organisms present critical issues of national security public health, and economic welfare. we still understand little about the zoonotic potential of many viruses. to this end, we are developing novel database tools to manage comparative genomic datasets. these tools add value because they allow us to summarize the direction, frequency and order of genomic changes. we will perform numerous real world tests with our tools with both avian influenza and coronavirus ...200718694075
signal amplification on a dna-tile-based biosensor with enhanced sensitivity.aims: herein, we report our work to improve the detection sensitivity of a dna-tile-based and self-assembled biosensing platform. this was achieved using hybridization chain reaction (hcr) as a signal amplifier on a water-soluble self-assembled dna nanoarray carrying detection probes. materials & methods: the fluorescence enhancement on the addition of specific detection targets was observed directly by confocal fluorescence microscopy. results & discussion: the versatility of the system was dem ...200818694314
variable oligomerization modes in coronavirus non-structural protein 9.non-structural protein 9 (nsp9) of coronaviruses is believed to bind single-stranded rna in the viral replication complex. the crystal structure of nsp9 of human coronavirus (hcov) 229e reveals a novel disulfide-linked homodimer, which is very different from the previously reported nsp9 dimer of sars coronavirus. in contrast, the structure of the cys69ala mutant of hcov-229e nsp9 shows the same dimer organization as the sars-cov protein. in the crystal, the wild-type hcov-229e protein forms a tr ...200818694760
polymorphisms in the c-type lectin genes cluster in chromosome 19 and predisposition to severe acute respiratory syndrome coronavirus (sars-cov) infection.polymorphisms of clec4m have been associated with predisposition for infection by the severe acute respiratory syndrome coronavirus (sars-cov). dc-signr, a c-type lectin encoded by clec4m, is a receptor for the virus. a variable number tandem repeat (vntr) polymorphism in its neck region was recently associated with susceptibility to sars infection. however, this association was controversial and was not supported by subsequent studies. two explanations may account for this discrepancy: (1) ther ...200818697825
dissection and identification of regions required to form pseudoparticles by the interaction between the nucleocapsid (n) and membrane (m) proteins of sars coronavirus.when expressed in mammalian cells, the nucleocapsid (n) and membrane (m) proteins of the severe acute respiratory syndrome coronavirus (sars-cov) are sufficient to form pseudoparticles. to identify region(s) of the n molecule required for pseudoparticle formation, we performed biochemical analysis of the interaction of n mutants and m in hek293 cells. using a peptide library derived from n, we found that amino acids 101-115 constituted a novel binding site for m. we examined the ability of n mut ...200818703211
molecular dynamic simulations analysis of ritonavir and lopinavir as sars-cov 3cl(pro) inhibitors.since the emergence of the severe acute respiratory syndrome (sars) to date, neither an effective antiviral drug nor a vaccine against sars is available. however, it was found that a mixture of two hiv-1 proteinase inhibitors, lopinavir and ritonavir, exhibited some signs of effectiveness against the sars virus. to understand the fine details of the molecular interactions between these proteinase inhibitors and the sars virus via complexation, molecular dynamics simulations were carried out for ...200818706430
a sars-cov protein, orf-6, induces caspase-3 mediated, er stress and jnk-dependent apoptosis.severe acute respiratory syndrome (sars) coronavirus (cov) spread from china to more than 30 countries, causing severe outbreaks of atypical pneumonia and over 800 deaths worldwide. cov primarily infects the upper respiratory and gastrointestinal tract; however, sars-cov has a unique pathogenesis because it infects both the upper and lower respiratory tracts and leads to human respiratory diseases. sars-cov genome has shown containing 14 open reading frames (orfs) and 8 of them encode novel prot ...200818708124
expression and functional characterisation of the putative sars coronavirus non-structural proteins x1-x5.1. we produced mammalian expression vectors encoding the sars coronavirus (sars-cov) accessory proteins with or without the fluorescence protein tag and cell lines with stable expression of these proteins. 2. the cellular localisation and function of the sars-cov accessory proteins was determined. 3. sars 6 and sars 8b proteins are localised to the endoplasmic reticulum and nucleus/cytoplasm, respectively, and both proteins stimulate host cell dna synthesis.200818708666
sars coronavirus and apoptosis.1. the adenovirus-mediated overexpression of sars coronavirus (sars-cov) spike protein (s) and its c-terminal domain (s2) induce apoptosis in vero e6 cells. 2. such apoptosis in vero e6 cells is time- and dose-dependent. 3. the adenovirus-mediated overexpression of sars-cov n-terminal domain (s1) and other structural proteins, including e,m and n protein, do not induce apoptosis.200818708667
molecular and genetic characterisation of the sars coronavirus auxiliary protein x1 in drosophila.1. we have generated monoclonal antibodies against the sars coronavirus (sars-cov) x1/3a protein (3a), which are suitable for western blotting, immunocytochemistry, and immunohistochemistry. 2. we have established and characterised an in-vivo 3a transgenic drosophila model, and demonstrated its usefulness in studying sars-cov 3a gene function. 3. we validated our in-vivo findings on 3a gene function in mammalian vero e6 cells. 4. our findings raise the possibility of using ion channel blockers a ...200818708668
risk-stratified seroprevalence of sars coronavirus in children residing in a district with point-source outbreak compared to a low-risk area.1. sars coronavirus has low transmissibility at the community level. 2. subclinical sars coronavirus infection is rare in children.200818708669
mechanisms of lymphocyte loss in sars coronavirus infection.1. human lymphocytes and monocytes are not permissive to productive sars coronavirus (sars-cov) infection in vitro. 2. challenge of lymphocytes and monocytes with infectious sars-cov, inactivated virions, and receptor-binding fragment of spike protein does not trigger apoptosis. 3. direct infection/interaction between viruses and lymphocytes/monocytes is unlikely to be the cause of lymphopaenia in sars patients. 4. lymphopaenia in sars patients is likely to result from indirect mechanisms second ...200818708670
investigation of immunogenic t-cell epitopes in sars virus nucleocapsid protein and their role in the prevention and treatment of sars infection.1. a novel hla-a2.1-specific sars coronavirus (sars-cov) nucleocapsid (n) protein epitope (n220-n228 lalllldrl) able to activate cytotoxic t cells in vitro has been identified. 2. when used with a single-chain-trimer system, the sars-cov n protein epitope (n220-n228 lalllldrl) can stimulate a cytotoxic t-cell response against n-protein expressing cells in the hla-a2.1k(b) transgenic mouse model.200818708671
role of polymorphisms of the inflammatory response genes and dc-signr in genetic susceptibility to sars and other infections.1. a genetic risk-association study involving more than 1200 subjects showed individuals homozygous for l-sign tandem repeats are less susceptible to sars infection. 2. this was supported by in vitro binding studies that demonstrated homozygous l-sign, compared to heterozygous, had higher binding capacity for sars coronavirus (sars-cov), with higher proteasome-dependent viral degradation. in contrast, homozygous l-sign demonstrated lower binding capacity for hiv1-gp120.3. genetic-association stu ...200818708672
helicases as antiviral drug targets.1. we have demonstrated for the first time that the helicase of a ribonucleic acid virus, the sars coronavirus (sars-cov), is a valid target for drug development. 2. using high throughput screen and chemical synthesis, several lead compounds targeting the sars-cov helicase have been identified. we have shown that these compounds can inhibit sars-cov helicase activity and viral growth in cell culture systems. these compounds can potentially be used to target other viruses.200818708673
studies of sars virus vaccines.1. intranasal vaccination using inactivated sars coronavirus (sars-cov) vaccine with adjuvant can induce strong systemic (serum immunoglobulin [ig] g) and respiratory tract local (tracheal-lung wash fluid iga) antibody responses with neutralising activity. 2. rbd-fc (protein-based vaccine) is able to induce effective neutralising antibodies able to provide protection from sars-cov infection in animal models. 3. a single dose of rbd-raav vaccination can induce adequate neutralising antibody again ...200818708674
an evaluation of sars and droplet infection control practices in acute and rehabilitation hospitals in hong kong.1. this study has demonstrated that great efforts have been made by the hospital authority and the studied hospital cluster to contain and prevent infection, and that high levels of vigilance have been enforced in anticipation of future outbreaks of sars and other droplet infections. 2. most health care workers and support workers have good hospital infection control and isolation precaution knowledge levels. 3. compliance with infection control guidelines is satisfactory and has increased compa ...200818708675
membrane insertion of the three main membranotropic sequences from sars-cov s2 glycoprotein.in order to complete the fusion process of sars-cov virus, several regions of the s2 virus envelope glycoprotein are necessary. recent studies have identified three membrane-active regions in the s2 domain of sars-cov glycoprotein, one situated downstream of the minimum furin cleavage, which is considered the fusion peptide (sarsfp), an internal fusion peptide located immediately upstream of the hr1 region (sarsifp) and the pre-transmembrane domain (sarsptm). we have explored the capacity of the ...200818721794
development of human single-chain antibodies against sars-associated coronavirus.the outbreak of severe acute respiratory syndrome (sars), caused by a distinct coronavirus, in 2003 greatly threatened public health in china, southeast asia as well as north america. over 1,000 patients died of the sars virus, representing 10% of infected people. like other coronaviruses, the sars virus also utilizes a surface glycoprotein, namely the spike protein, to infect host cells. the spike protein of sars virus consists of 1,255 amino acid residues and can be divided into two sub-domain ...200818724064
the m, e, and n structural proteins of the severe acute respiratory syndrome coronavirus are required for efficient assembly, trafficking, and release of virus-like particles.the production of virus-like particles (vlps) constitutes a relevant and safe model to study molecular determinants of virion egress. the minimal requirement for the assembly of vlps for the coronavirus responsible for severe acute respiratory syndrome in humans (sars-cov) is still controversial. recent studies have shown that sars-cov vlp formation depends on either m and e proteins or m and n proteins. here we show that both e and n proteins must be coexpressed with m protein for the efficient ...200818753196
severe acute respiratory syndrome vaccine efficacy in ferrets: whole killed virus and adenovirus-vectored vaccines.although the 2003 severe acute respiratory syndrome (sars) outbreak was controlled, repeated transmission of sars coronavirus (cov) over several years makes the development of a sars vaccine desirable. we performed a comparative evaluation of two sars vaccines for their ability to protect against live sars-cov intranasal challenge in ferrets. both the whole killed sars-cov vaccine (with and without alum) and adenovirus-based vectors encoding the nucleocapsid (n) and spike (s) protein induced neu ...200818753223
[antiviral activity of arbidol and its derivatives against the pathogen of severe acute respiratory syndrome in the cell cultures].experimental studies of arbidol and arbidol mesylate versus ribavirin suggest that insertion of these agents into the nutrient medium of the cultured cells gmk-ah-1 (d) after infection at concentrations of 50, 25, and 100 microg/ml, respectively, is effective in suppressing the reproduction of severe acute respiratory syndrome (sars) virus. arbidol and arbidol mesylate were shown to have a direct antiviral effect in early viral replication in the cultured cells. the promising antiviral agent is ...200818756809
steroid-induced osteonecrosis: the number of lesions is related to the dosage.severe acute respiratory syndrome (sars) is a newly described infectious disease caused by the sars coronavirus which attacks the immune system and pulmonary epithelium. it is treated with regular high doses of corticosteroids. our aim was to determine the relationship between the dosage of steroids and the number and distribution of osteonecrotic lesions in patients treated with steroids during the sars epidemic in beijing, china in 2003. we identified 114 patients for inclusion in the study. o ...200818757967
an immunosuppressed syrian golden hamster model for sars-cov infection.several small animal models have been developed for the study of severe acute respiratory syndrome coronavirus (sars-cov) replication and pathogenesis. syrian golden hamsters are among the best small animal models, though little clinical illness and no mortality are observed after virus infection. cyclophosphamide was used to immunosuppress hamsters leading to a prolonged disease course and higher mortality after sars-cov infection. in addition, there was a significant weight loss, expanded tiss ...200818760437
an immunosuppressed syrian golden hamster model for sars-cov infection.several small animal models have been developed for the study of severe acute respiratory syndrome coronavirus (sars-cov) replication and pathogenesis. syrian golden hamsters are among the best small animal models, though little clinical illness and no mortality are observed after virus infection. cyclophosphamide was used to immunosuppress hamsters leading to a prolonged disease course and higher mortality after sars-cov infection. in addition, there was a significant weight loss, expanded tiss ...200818760437
toona sinensis roem tender leaf extract inhibits sars coronavirus replication.severe acute respiratory syndrome (sars) is a life-threatening disease caused by the sars coronavirus (sars-cov). the development of new antiviral agents for sars-cov is an important issue. we tried to find potential resource from traditional chinese medicine (tcm) for development of new drugs against sars-cov.200818762235
severe acute respiratory syndrome coronavirus elicits a weak interferon response compared to traditional interferon-inducing viruses.the aim of the present study is to investigate changes of interferon (ifn) production occurring over the first 48 h after infection of peripheral blood mononuclear cells (pbmcs) with severe acute respiratory syndrome (sars) coronavirus (cov) and to compare these changes to those induced by well-established ifn-inducing viruses, such as vesicular stomatitis (vsv) and newcastle viruses (ndv). experiments have been carried out using pbmcs of 10 different healthy donors. the results showed that the ...200818781076
entry from the cell surface of severe acute respiratory syndrome coronavirus with cleaved s protein as revealed by pseudotype virus bearing cleaved s protein.severe acute respiratory syndrome (sars) coronavirus (sars-cov) is known to take an endosomal pathway for cell entry; however, it is thought to enter directly from the cell surface when a receptor-bound virion spike (s) protein is affected by trypsin, which induces cleavage of the s protein and activates its fusion potential. this suggests that sars-cov bearing a cleaved form of the s protein can enter cells directly from the cell surface without trypsin treatment. to explore this possibility, w ...200818786990
interactions between m protein and other structural proteins of severe, acute respiratory syndrome-associated coronavirus.severe acute respiratory syndrome-associated coronavirus (sars-cov) structural proteins (s, e, m, and nc) localize in different subcellular positions when expressed individually. however, sars-cov m protein is co-localized almost entirely with s, e, or nc protein when co-expressed in the cells. on the other hand, only partial co-localization was observed when s and e, s and nc, or e and nc were co-expressed in the cells. interactions between sars-cov m and other structural proteins but not inter ...200818792806
design, synthesis and antiviral efficacy of a series of potent chloropyridyl ester-derived sars-cov 3clpro inhibitors.design, synthesis and biological evaluation of a series of 5-chloropyridine ester-derived severe acute respiratory syndrome-coronavirus chymotrypsin-like protease inhibitors is described. position of the carboxylate functionality is critical to potency. inhibitor 10 with a 5-chloropyridinyl ester at position 4 of the indole ring is the most potent inhibitor with a sars-cov 3clpro ic(50) value of 30 nm and an antiviral ec(50) value of 6.9 microm. molecular docking studies have provided possible b ...200818796354
sars-coronavirus replication is supported by a reticulovesicular network of modified endoplasmic reticulum.positive-strand rna viruses, a large group including human pathogens such as sars-coronavirus (sars-cov), replicate in the cytoplasm of infected host cells. their replication complexes are commonly associated with modified host cell membranes. membrane structures supporting viral rna synthesis range from distinct spherular membrane invaginations to more elaborate webs of packed membranes and vesicles. generally, their ultrastructure, morphogenesis, and exact role in viral replication remain to b ...200818798692
rhesus angiotensin converting enzyme 2 supports entry of severe acute respiratory syndrome coronavirus in chinese macaques.angiotensin converting enzyme 2 (ace2) is the receptor that severe acute respiratory syndrome coronavirus (sars-cov) utilizes for target cell entry and, therefore, plays an important role in sars pathogenesis. since chinese rhesus (rh) macaques do not usually develop sars after sars-cov infection, it has been suggested that rh-ace2 probably does not support viral entry efficiently. to determine the role of rh-ace2 in early lung pathogenesis in vivo, we studied eleven chinese rhesus monkeys exper ...200818801550
rhesus angiotensin converting enzyme 2 supports entry of severe acute respiratory syndrome coronavirus in chinese macaques.angiotensin converting enzyme 2 (ace2) is the receptor that severe acute respiratory syndrome coronavirus (sars-cov) utilizes for target cell entry and, therefore, plays an important role in sars pathogenesis. since chinese rhesus (rh) macaques do not usually develop sars after sars-cov infection, it has been suggested that rh-ace2 probably does not support viral entry efficiently. to determine the role of rh-ace2 in early lung pathogenesis in vivo, we studied eleven chinese rhesus monkeys exper ...200818801550
a prime-boost vaccination protocol optimizes immune responses against the nucleocapsid protein of the sars coronavirus.severe acute respiratory syndrome (sars) is a serious infectious disease caused by the sars coronavirus. we assessed the potential of prime-boost vaccination protocols based on the nucleocapsid (nc) protein co-administered with a derivative of the mucosal adjuvant malp-2 or expressed by modified vaccinia virus ankara (mva-nc) to stimulate humoral and cellular immune responses at systemic and mucosal levels. the obtained results demonstrated that strong immune responses can be elicited both at sy ...200818805454
risk factors for sars infection within hospitals in hanoi, vietnam.we investigated a nosocomial infection of severe acute respiratory syndrome (sars) in vietnam in 2003 and attempted to identify risk factors for sars infection. of the 146 subjects who came into contact with sars patients at hospital a, 43 (29.5%) developed sars, and an additional 16 (11%) were asymptomatic but sars-coronavirus (cov) seropositive. the asymptomatic infection rate accounted for 15.5% of the total number of infected patients at hospital a, which was higher than that of 6.5% observe ...200818806349
importance of cholesterol-rich membrane microdomains in the interaction of the s protein of sars-coronavirus with the cellular receptor angiotensin-converting enzyme 2.cholesterol present in the plasma membrane of target cells has been shown to be important for the infection by sars-cov. we show that cholesterol depletion by treatment with methyl-beta-cyclodextrin (m beta cd) affects infection by sars-cov to the same extent as infection by vesicular stomatitis virus-based pseudotypes containing the surface glycoprotein s of sars-cov (vsv-delta g-s). therefore, the role of cholesterol for sars-cov infection can be assigned to the s protein and is unaffected by ...200818814896
systematic assembly of a full-length infectious clone of human coronavirus nl63.historically, coronaviruses were predominantly associated with mild upper respiratory disease in humans. more recently, three novel coronaviruses associated with severe human respiratory disease were found, including (i) the severe acute respiratory syndrome coronavirus, associated with a significant atypical pneumonia and 10% mortality; (ii) hku-1, associated with chronic pulmonary disease; and (iii) nl63, associated with both upper and lower respiratory tract disease in children and adults wor ...200818818320
inhibition of the interaction between the sars-cov spike protein and its cellular receptor by anti-histo-blood group antibodies.severe acute respiratory syndrome coronavirus (sars-cov) is a highly pathogenic emergent virus which replicates in cells that can express abh histo-blood group antigens. the heavily glycosylated sars-cov spike (s) protein binds to angiotensin-converting enzyme 2 which serves as a cellular receptor. epidemiological analysis of a hospital outbreak in hong kong revealed that blood group o was associated with a low risk of infection. in this study, we used a cellular model of adhesion to investigate ...200818818423
inhibition of the interaction between the sars-cov spike protein and its cellular receptor by anti-histo-blood group antibodies.severe acute respiratory syndrome coronavirus (sars-cov) is a highly pathogenic emergent virus which replicates in cells that can express abh histo-blood group antigens. the heavily glycosylated sars-cov spike (s) protein binds to angiotensin-converting enzyme 2 which serves as a cellular receptor. epidemiological analysis of a hospital outbreak in hong kong revealed that blood group o was associated with a low risk of infection. in this study, we used a cellular model of adhesion to investigate ...200818818423
new respiratory viruses of humans.acute respiratory viruses are a major cause of morbidity and mortality in humans worldwide and most acute respiratory infections are caused by viruses. many of these viruses cause the highest burden of disease in specific risk groups such as young infants, the elderly, and immune-compromised individuals. although the most important respiratory viruses of humans have been identified in the last century, in the past decade about a dozen "new" viruses have been discovered that may cause a high burd ...200818820582
a sars dna vaccine induces neutralizing antibody and cellular immune responses in healthy adults in a phase i clinical trial.the severe acute respiratory syndrome (sars) virus is a member of the coronaviridae (cov) family that first appeared in the guangdong province of china in 2002 and was recognized as an emerging infectious disease in march 2003. over 8000 cases and 900 deaths occurred during the epidemic. we report the safety and immunogenicity of a sars dna vaccine in a phase i human study.200818824060
design and synthesis of cinanserin analogs as severe acute respiratory syndrome coronavirus 3cl protease inhibitors.the severe acute respiratory syndrome (sars) coronavirus 3cl protease is an attractive target for the development of anti-sars drugs. in this paper, cinanserin (1) analogs were synthesized and tested for the inhibitory activities against sars-coronavirus (cov) 3cl protease by fluorescence resonance energy transfer (fret) assay. four analogs show significant activities, especially compound 26 with an ic(50) of 1.06 microm.200818827378
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