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the aetiology of sars: koch's postulates fulfilled.proof that a newly identified coronavirus, severe acute respiratory syndrome coronavirus (sars-cov) is the primary cause of severe acute respiratory syndrome (sars) came from a series of studies on experimentally infected cynomolgus macaques (macaca fascicularis). sars-cov-infected macaques developed a disease comparable to sars in humans; the virus was re-isolated from these animals and they developed sars-cov-specific antibodies. this completed the fulfilment of koch's postulates, as modified ...200415306393
the aetiology of sars: koch's postulates fulfilled.proof that a newly identified coronavirus, severe acute respiratory syndrome coronavirus (sars-cov) is the primary cause of severe acute respiratory syndrome (sars) came from a series of studies on experimentally infected cynomolgus macaques (macaca fascicularis). sars-cov-infected macaques developed a disease comparable to sars in humans; the virus was re-isolated from these animals and they developed sars-cov-specific antibodies. this completed the fulfilment of koch's postulates, as modified ...200415306393
laboratory diagnosis of sars.the emergence of new viral infections of man requires the development of robust diagnostic tests that can be applied in the differential diagnosis of acute illness, or to determine past exposure, so as to establish the true burden of disease. since the recognition in april 2003 of the severe acute respiratory syndrome coronavirus (sars-cov) as the causative agent of severe acute respiratory syndrome (sars), enormous efforts have been applied to develop molecular and serological tests for sars wh ...200415306394
epidemiology, transmission dynamics and control of sars: the 2002-2003 epidemic.this paper reviews current understanding of the epidemiology, transmission dynamics and control of the aetiological agent of severe acute respiratory syndrome (sars). we present analyses of data on key parameters and distributions and discuss the processes of data capture, analysis and public health policy formulation during the sars epidemic are discussed. the low transmissibility of the virus, combined with the onset of peak infectiousness following the onset of clinical symptoms of disease, t ...200415306395
animal origins of sars coronavirus: possible links with the international trade in small carnivores.the search for animal host origins of severe acute respiratory syndrome (sars) coronavirus has so far remained focused on wildlife markets, restaurants and farms within china. a significant proportion of this wildlife enters china through an expanding regional network of illegal, international wildlife trade. we present the case for extending the search for ancestral coronaviruses and their hosts across international borders into countries such as vietnam and lao people's democratic republic, wh ...200415306396
sequential changes of serum aminotransferase levels in patients with severe acute respiratory syndrome.severe acute respiratory syndrome (sars) is a newly emerging infectious disease. to describe the hepatic injury caused by this disease, we report the sequential changes of serum transaminase in probable sars patients during a hospital outbreak in southern taiwan. from april to june, 2003, 52 probable sars patients were hospitalized. serial serum aspartate aminotransferase (ast) and alanine aminotransferase (alt) levels were retrospectively analyzed and hepatitis b surface antigen (hbsag) was als ...200415306699
value of initial chest radiographs for predicting clinical outcomes in patients with severe acute respiratory syndrome.to determine whether the initial chest radiograph is helpful in predicting the clinical outcome of patients with severe acute respiratory syndrome (sars).200415308434
retroviral vectors pseudotyped with severe acute respiratory syndrome coronavirus s protein.the worldwide outbreak of severe acute respiratory syndrome (sars) was shown to be associated with a novel coronavirus (cov) now called sars cov. we report here the generation of sars cov s protein-pseudotyped murine leukemia virus (mlv) vector particles. the wild-type s protein pseudotyped mlv vectors, although at a low efficiency. partial deletion of the cytoplasmic tail of s dramatically increased infectivity of pseudotypes, with titers only two- to threefold lower than those of pseudotypes g ...200415308697
epidemiology of sars: the missing pathogen? 200415310809
severe acute respiratory syndrome (sars) and the gdp. part ii: implications for gdps.the transmission modes of sars-coronavirus appear to be through droplet spread, close contact and fomites although air borne transmission has not been ruled out. this clearly places dental personnel at risks as they work in close proximity to their patients employing droplet and aerosol generating procedures. although the principle of universal precautions is widely advocated and followed throughout the dental community, additional precautionary measures - termed standard precaution may be neces ...200415311240
[detection of rna of sars coronavirus in hospital sewage].in order to explore the existence of sars coronavirus (co-v) and/or its rna in sewage of hospitals administered sars patients.200415312586
characterization of the 3a protein of sars-associated coronavirus in infected vero e6 cells and sars patients.proteomics was used to identify a protein encoded by orf 3a in a sars-associated coronavirus (sars-cov). immuno-blotting revealed that interchain disulfide bonds might be formed between this protein and the spike protein. elisa indicated that sera from sars patients have significant positive reactions with synthesized peptides derived from the 3a protein. these results are concordant with that of a spike protein-derived peptide. a tendency exists for co-mutation between the 3a protein and the sp ...200415312778
oligomerization of the sars-cov s glycoprotein: dimerization of the n-terminus and trimerization of the ectodomain.viral envelope glycoproteins are oligomeric and the quaternary structure is critical for their membrane fusion activity. typically the transmembrane glycoproteins of class i fusion proteins contain the oligomerization domains and the surface glycoproteins (su) are monomeric. however, it has been previously demonstrated [j. biol. chem. 277 (2002) 19727] that the su of a murine hepatitis coronavirus (mhv) forms dimers, the dimerization domain overlaps the receptor-binding domain (rbd) and that thi ...200415313178
a subcutaneously injected uv-inactivated sars coronavirus vaccine elicits systemic humoral immunity in mice.the recent emergence of severe acute respiratory syndrome (sars) was caused by a novel coronavirus, sars-cov. it spread rapidly to many countries and developing a sars vaccine is now urgently required. in order to study the immunogenicity of uv-inactivated purified sars-cov virion as a vaccine candidate, we subcutaneously immunized mice with uv-inactivated sars-cov with or without an adjuvant. we chose aluminum hydroxide gel (alum) as an adjuvant, because of its long safety history for human use ...200415314040
infection of cultured intestinal epithelial cells with severe acute respiratory syndrome coronavirus.to identify a model for the study of intestinal pathogenesis of severe acute respiratory syndrome (sars) we tested the sensitivity of six human intestinal epithelial cell lines to infection with sars coronavirus (sars-cov). in permissive cell lines, effects of sars-cov on cellular gene expression were analysed using high-density oligonucleotide arrays. caco-2 and cl-14 cell lines were found to be highly permissive to sars-cov, due to the presence of angiotensin-converting enzyme 2 as a functiona ...200415316659
a candidate vaccine for severe acute respiratory syndrome. 200415317899
neutralizing antibodies in patients with severe acute respiratory syndrome-associated coronavirus infection.severe acute respiratory syndrome (sars)-associated coronavirus (sars-cov) is the principal etiologic agent of sars. we analyzed serum samples obtained from 623 patients with sars in beijing, to determine whether infection with sars-cov can elicit neutralizing antibodies (nabs).200415319862
direct sequencing of sars-coronavirus s and n genes from clinical specimens shows limited variation.severe acute respiratory syndrome-associated coronavirus (sars-cov) emerged, in november 2002, as a novel agent causing severe respiratory illness. to study sequence variation in the sars-cov genome, we determined the nucleic acid sequence of the s and n genes directly from clinical specimens from 10 patients--1 specimen with no matched sars-cov isolate, from 2 patients; multiple specimens from 3 patients; and matched clinical-specimen/cell-culture-isolate pairs from 6 patients. we identified 3 ...200415319863
low stability of nucleocapsid protein in sars virus.the nucleocapsid protein (n protein) is one of the major virion structural proteins of a newly identified coronavirus, which has been confirmed as the causative agent of severe acute respiratory syndrome (sars). the major function of n protein is to assemble the rna of coronavirus. in the present study, the gene encoding the n protein was cloned and the protein was expressed, purified, and refolded as shown by (1)h nmr measurement. the maximal trp emission wavelength occurs near 331 nm, suggesti ...200415323569
sars control and psychological effects of quarantine, toronto, canada.as a transmissible infectious disease, severe acute respiratory syndrome (sars) was successfully contained globally by instituting widespread quarantine measures. although these measures were successful in terminating the outbreak in all areas of the world, the adverse effects of quarantine have not previously been determined in a systematic manner. in this hypothesis-generating study supported by a convenience sample drawn in close temporal proximity to the period of quarantine, we examined the ...200415324539
detection of sars-associated coronavirus in throat wash and saliva in early diagnosis.the severe acute respiratory syndrome-associated coronavirus (sars-cov) is thought to be transmitted primarily through dispersal of droplets, but little is known about the load of sars-cov in oral droplets. we examined oral specimens, including throat wash and saliva, and found large amounts of sars-cov rna in both throat wash (9.58 x 10(2) to 5.93 x 10(6) copies/ml) and saliva (7.08 x 10(3) to 6.38 x 10(8) copies/ml) from all specimens of 17 consecutive probable sars case-patients, supporting t ...200415324540
collecting data to assess sars interventions.with cases of severe acute respiratory syndrome (sars) occurring across geographic regions, data collection on the effectiveness of intervention strategies should be standardized to facilitate analysis. we propose a minimum dataset to capture data needed to examine the basic reproduction rate, case status and criteria, symptoms, and outcomes of sars.200415324551
mice susceptible to sars coronavirus.murine models of severe acute respiratory syndrome-associated coronavirus (sars-cov) will greatly advance research on this emerging virus. when balb/c mice were simultaneously inoculated intranasally and orally, replication of sars-cov was found in both lung and intestinal tissue.200415324552
sars coronavirus detection.we developed a set of three real-time reverse transcription-polymerase chain reaction (pcr) assays that amplify three different regions of the sars-associated coronavirus (sars-cov), can be run in parallel or in a single tube, and can detect <10 genome equivalents of sars-cov. the assays consider all currently available sars-cov sequences and are optimized for two prominent real-time pcr platforms.200415324554
human sars-coronavirus rna-dependent rna polymerase: activity determinants and nucleoside analogue inhibitors. 200415326590
the 17th international conference on antiviral research.the focus of the 17th international conference on antiviral research was the discovery and development of antiviral agents (chemistry, biology, animal models and clinical trial results) against a variety of human infectious agents including hiv, herpes viruses, hepatitis viruses, respiratory viruses and emerging/re-emerging pathogens. the meeting included the symposium 'clinical update on antiviral drugs', plenary sessions dedicated to each of the individual classes of infectious agents, a sympo ...200415330752
ace2 gene polymorphisms do not affect outcome of severe acute respiratory syndrome. 200415331509
identification and characterization of severe acute respiratory syndrome coronavirus replicase proteins.the severe acute respiratory syndrome coronavirus (sars-cov) encodes proteins required for rna transcription and genome replication as large polyproteins that are proteolytically processed by virus-encoded proteinases to produce mature replicase proteins. in this report, we generated antibodies against sars-cov predicted replicase protein and used the antibodies to identify and characterize 12 of the 16 predicted mature replicase proteins (nsp1, nsp2, nsp3, nsp4, nsp5, nsp8, nsp9, nsp12, nsp13, ...200415331731
transporting patient with suspected sars. 200415338533
psychosocial impact of sars. 200415338536
emerging infections: what have we learned from sars? 200415338569
[distribution and timing of antibody to sars-cov in sars cases of transmission chain or non-transmission chain].to find out the timing of serologic responses after illness onset and distribution of igg antibody to sars-cov in sars cases of transmission chain or non-transmission chain.200415340494
[studies on igg antibodies of sars patients].to investigate the significance of detecting specific serum igg antibodies in clinical diagnosis of sars as well as affecting factors.200415340527
[comparative study of clinical characteristics and prognosis of clinically diagnosed sars patients with positive and negative serum sars coronavirus-specific antibodies test].to investigate clinical characteristics and long-term effects of sars.200415130303
[covert infection of severe acute respiratory syndrome in health-care professionals and its relation to the workload and the type of work].to study severe acute respiratory syndrome (sars) covert infection in health-care professionals and its relation to work intensity and type of work.200415130323
heterogeneity detector: finding heterogeneous positions in phred/phrap assemblies.a modification to phred and program to detect heterogeneous positions, which is particularly useful in the identification of mutations and other abnormalities in phred/phrap genome assemblies. availability: the package is made available at http://glscompute.gis.a-star.edu.sg/~charlie/dhetero.html200415130927
development and evaluation of a novel loop-mediated isothermal amplification method for rapid detection of severe acute respiratory syndrome coronavirus.the development and evaluation of a one-step single-tube accelerated real-time quantitative reverse transcription (rt) loop-mediated isothermal amplification (lamp) assay is reported for rapid detection of the severe acute respiratory syndrome coronavirus (sars-cov) replicase gene. a total of 49 samples (15 throat washes, 13 throat swabs, and 21 combined throat and nasal swabs) collected from patients admitted to the hanoi-french and ninhbinh hospitals in vietnam during the sars epidemic were ev ...200415131154
reverse transcriptase pcr diagnostic assay for the coronavirus associated with severe acute respiratory syndrome.recent outbreaks of severe acute respiratory syndrome (sars) have spurred intense research efforts around the world to deal with the serious threat to health posed by this novel coronavirus. a rapid, reliable diagnostic assay is needed for monitoring the spread of the disease. here we report a method for eliminating false-negative results and increasing test sensitivity, based on the hypothesis that the message encoded by the nucleocapsid (n) gene is the most abundant during viral infection. nas ...200415131160
evaluation of advanced reverse transcription-pcr assays and an alternative pcr target region for detection of severe acute respiratory syndrome-associated coronavirus.first-generation reverse transcription-pcr (rt-pcr) assays for severe acute respiratory syndrome-associated coronavirus (sars-cov) gave false-negative results in a considerable fraction of patients. in the present study, we evaluated two second-generation, replicase (r) gene-based, real-time rt-pcr test kits--the realart hpa coronavirus lc kit (artus, hamburg, germany) and the lightcycler sars-cov quantification kit (roche, penzberg, germany)--and a real-time rt-pcr assay for the nucleocapsid (n ...200415131168
comparison of two real-time quantitative assays for detection of severe acute respiratory syndrome coronavirus.the new severe acute respiratory syndrome (sars) coronavirus (cov), described in february 2003, infected a total of 8,439 people. a total of 812 people died due to respiratory insufficiency. close contact with symptomatic patients appeared to be the main route of transmission. however, potential transmission by blood transfusion could not be definitely excluded. two real-time sars-specific pcr assays were assessed for their sensitivities, agreement of test results, and intra-assay variabilities. ...200415131175
detection of specific antibodies to severe acute respiratory syndrome (sars) coronavirus nucleocapsid protein for serodiagnosis of sars coronavirus pneumonia.we report the evaluation of recombinant severe acute respiratory syndrome (sars) coronavirus (sars-cov) nucleocapsid protein enzyme-linked immunosorbent assay (elisa)-based antibody tests for serodiagnosis of sars-cov pneumonia and compare the sensitivities and specificities of this elisa for detection of immunoglobulin g (igg), igm, iga, and their combinations with serum samples from 149 healthy blood donors who donated blood 3 years ago as controls and 106 sars-cov pneumonia patients in hong k ...200415131220
antigenic cross-reactivity between the nucleocapsid protein of severe acute respiratory syndrome (sars) coronavirus and polyclonal antisera of antigenic group i animal coronaviruses: implication for sars diagnosis. 200415131233
[study on the correlation between positive rates of sars rna in clinical confirmed sars patients and the appearance of rna in relation to the development of the disease].to study the correlation between positive rates of rna in clinical confirmed severe acute respiratory syndrome (sars) patients and its appearance in relation to the development of the disease in order to provide scientific basis for early diagnosis, effective prevention and treatment of the disease.200415132863
evaluation of homology modeling of the severe acute respiratory syndrome (sars) coronavirus main protease for structure based drug design.to accelerate the development of drugs against severe acute respiratory syndrome (sars), we constructed a homology model of the sars coronavirus main protease using our modeling software, fams ligand&complex, and released it before the x-ray structure was solved. the x-ray structure showed our model as accurately predicted and useful for structure based drug design.200415133227
[new developments as regards coronaviruses]. 200415134085
probing the structure of the sars coronavirus using scanning electron microscopy.a novel coronavirus, sars-cov, has been confirmed to be the aetiological agent of sars. transmission electron microscope (tem) images played an important role in initial identification of the pathogen. in order to obtain greater morphological detail of sars-cov than could be obtained by tem, we used ultra-high resolution scanning electron microscopy (sem) to image the virus particles. we show here the three-dimensional appearance of sars-cov. enhanced detail of the ultrastructure reveals the tri ...200415134191
identification of a novel protein 3a from severe acute respiratory syndrome coronavirus.the open reading frame 3 of the severe acute respiratory syndrome coronavirus (sars-cov) genome encodes a predicted protein 3a, consisting of 274 amino acids, that lacks any significant similarities to any known protein. we generated specific antibodies against sars protein 3a by using a synthetic peptide (p2) corresponding to amino acids 261-274 of the putative protein. anti-p2 antibodies and the sera from sars patients could specifically detect the recombinant sars protein 3a expressed in esch ...200415135062
the antiviral effect of interferon-beta against sars-coronavirus is not mediated by mxa protein.severe acute respiratory syndrome (sars) is caused by a novel coronavirus termed sars-cov. no antiviral treatment has been established so far. interferons are cytokines which induce the synthesis of several antivirally active proteins in the cell. in this study, we demonstrated that multiplication of sars-cov in cell culture can be strongly inhibited by pretreatment with interferon-beta. interferon-alpha and interferon-gamma, by contrast, were less effective. the human mxa protein is one of the ...200415135736
a one step quantitative rt-pcr for detection of sars coronavirus with an internal control for pcr inhibitors.in this study, we report a one step quantitative rt-pcr assay for severe acute respiratory syndrome (sars) diagnosis. the overall detection rate for clinical samples collected from days 1 to 9 of disease onset is 86.2% and the specificity of the assay is 100%. to detect false negative results due to pcr inhibitors or faulty rna extraction, we have further modified this one step rt-pcr assay for simultaneous detection of severe acute respiratory syndrome (sars) coronavirus (cov) and 18s ribosomal ...200415135737
severe acute respiratory syndrome (sars): a review.severe acute respiratory syndrome (sars) is a newly emerged disease that rapidly spread around the world. the disease originated in southern china and a novel coronavirus (sars cov) has been implicated as the causative organism. the path this virus took to set up human infection remains a mystery, though preliminary data point to origins in an animal reservoir. nosocomial transmission of sars cov has been a striking feature in this epidemic. the clinical illness is similar to many acute respirat ...200415139736
t-cell epitopes in severe acute respiratory syndrome (sars) coronavirus spike protein elicit a specific t-cell immune response in patients who recover from sars.the immunogenicity of hla-a2-restricted t-cell epitopes in the s protein of the severe acute respiratory syndrome coronavirus (sars-cov) and of human coronavirus strain 229e (hcov-229e) was analyzed for the elicitation of a t-cell immune response in donors who had fully recovered from sars-cov infection. we employed online database analysis to compare the differences in the amino acid sequences of the homologous t epitopes of hcov-229e and sars-cov. the identified t-cell epitope peptides were sy ...200415140958
multiple enzymatic activities associated with severe acute respiratory syndrome coronavirus helicase.severe acute respiratory syndrome coronavirus (sars-cov), a newly identified group 2 coronavirus, is the causative agent of severe acute respiratory syndrome, a life-threatening form of pneumonia in humans. coronavirus replication and transcription are highly specialized processes of cytoplasmic rna synthesis that localize to virus-induced membrane structures and were recently proposed to involve a complex enzymatic machinery that, besides rna-dependent rna polymerase, helicase, and protease act ...200415140959
ph-dependent entry of severe acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer through dc-sign.the severe acute respiratory syndrome coronavirus (sars-cov) synthesizes several putative viral envelope proteins, including the spike (s), membrane (m), and small envelope (e) glycoproteins. although these proteins likely are essential for viral replication, their specific roles in sars-cov entry have not been defined. in this report, we show that the sars-cov s glycoprotein mediates viral entry through ph-dependent endocytosis. further, we define its cellular tropism and demonstrate that virus ...200415140961
organ distribution of severe acute respiratory syndrome (sars) associated coronavirus (sars-cov) in sars patients: implications for pathogenesis and virus transmission pathways.we previously identified the major pathological changes in the respiratory and immune systems of patients who died of severe acute respiratory syndrome (sars) but gained little information on the organ distribution of sars-associated coronavirus (sars-cov). in the present study, we used a murine monoclonal antibody specific for sars-cov nucleoprotein, and probes specific for a sars-cov rna polymerase gene fragment, for immunohistochemistry and in situ hybridization, respectively, to detect sars- ...200415141376
tissue distribution of ace2 protein, the functional receptor for sars coronavirus. a first step in understanding sars pathogenesis.severe acute respiratory syndrome (sars) is an acute infectious disease that spreads mainly via the respiratory route. a distinct coronavirus (sars-cov) has been identified as the aetiological agent of sars. recently, a metallopeptidase named angiotensin-converting enzyme 2 (ace2) has been identified as the functional receptor for sars-cov. although ace2 mrna is known to be present in virtually all organs, its protein expression is largely unknown. since identifying the possible route of infecti ...200415141377
re: to kf, tong jh, chan pk, et al. tissue and cellular tropism of the coronavirus associated with severe acute respiratory syndrome: an in-situ hybridization study of fatal cases. j pathol 2004; 202: 157-163. 200415141389
sars in the intensive care unit.approximately 20% of patients with severe acute respiratory syndrome (sars) develop respiratory failure that requires admission to an intensive care unit (icu). old age, comorbidity, and elevated lactate dehydrogenase on hospital admission are associated with increased risk for icu admission. icu admission usually is late and occurs 8 to 10 days after symptom onset. acute respiratory distress syndrome occurs in almost all admitted patients and most require mechanical ventilation. icu admission i ...200415142487
hiv protease inhibitor nelfinavir inhibits replication of sars-associated coronavirus.a novel coronavirus has been identified as an etiological agent of severe acute respiratory syndrome (sars). to rapidly identify anti-sars drugs available for clinical use, we screened a set of compounds that included antiviral drugs already in wide use. here we report that the hiv-1 protease inhibitor, nelfinavir, strongly inhibited replication of the sars coronavirus (sars-cov). nelfinavir inhibited the cytopathic effect induced by sars-cov infection. expression of viral antigens was much lowe ...200415144898
structure of the n-terminal rna-binding domain of the sars cov nucleocapsid protein.the severe acute respiratory syndrome (sars) virus belongs to the coronaviridea family of viruses. its virion encodes several proteins including a replicase and four structural proteins. here we describe the three-dimensional structure of the n-terminal domain of the sars coronavirus (cov) nucleocapsid protein. the protein consists of a five-stranded beta sheet with a folding topology distinct from other rna-binding proteins. single-stranded rnas bind to the protein surface at the junction betwe ...200415147189
assembly of human severe acute respiratory syndrome coronavirus-like particles.viral particles of human severe acute respiratory syndrome coronavirus (sars cov) consist of three virion structural proteins, including spike protein, membrane protein, and envelope protein. in this report, virus-like particles were assembled in insect cells by the co-infection with recombinant baculoviruses, which separately express one of these three virion proteins. we found that the membrane and envelope proteins are sufficient for the efficient formation of virus-like particles and could b ...200415147946
characterization of sars main protease and inhibitor assay using a fluorogenic substrate.sars main protease is essential for life cycle of sars coronavirus and may be a key target for developing anti-sars drugs. recently, the enzyme expressed in escherichia coli was characterized using a hplc assay to monitor the formation of products from 11 peptide substrates covering the cleavage sites found in the sars viral genome. this protease easily dissociated into inactive monomer and the deduced kd of the dimer was 100 microm. in order to detect enzyme activity, the assay needed to be per ...200415147951
severe acute respiratory syndrome coronavirus (sars-cov) infection inhibition using spike protein heptad repeat-derived peptides.the coronavirus sars-cov is the primary cause of the life-threatening severe acute respiratory syndrome (sars). with the aim of developing therapeutic agents, we have tested peptides derived from the membrane-proximal (hr2) and membrane-distal (hr1) heptad repeat region of the spike protein as inhibitors of sars-cov infection of vero cells. it appeared that hr2 peptides, but not hr1 peptides, were inhibitory. their efficacy was, however, significantly lower than that of corresponding hr2 peptide ...200415150417
sars: the first pandemic of the 21st century. 200415152053
virtual screening for sars-cov protease based on kz7088 pharmacophore points.pharmacophore modeling can provide valuable insight into ligand-receptor interactions. it can also be used in 3d (dimensional) database searching for potentially finding biologically active compounds and providing new research ideas and directions for drug-discovery projects. to stimulate the structure-based drug design against sars (severe acute respiratory syndrome), a pharmacophore search was conducted over 3.6 millions of compounds based on the atomic coordinates of the complex obtained by d ...200415154780
severe acute respiratory syndrome: review and lessons of the 2003 outbreak. 200415155694
infectious diseases. one year after outbreak, sars virus yields some secrets. 200415155925
severe acute respiratory syndrome.the first cases of severe acute respiratory syndrome (sars) occurred in china in november 2002. the agent causing this illness has been identified as a novel coronavirus, sars-coronavirus. since its introduction <1 year ago, this virus has infected 8098 people in 26 countries, killing 774 of them. we present an overview of the epidemiology, clinical presentation, diagnosis, and treatment of sars based on the current state of knowledge derived from published studies and our own personal experienc ...200415156481
[determination and comparison of anti-sars antibody in children and adults].to investigate the positive rate of anti-sars antibody in children and adults without sars, 197 paediatric patients under 14 years old from inpatient and outpatient department of our hospital, 156 healthy children pupils from primary school, 453 adult patients over 18 years old from inpatient and outpatient department of our hospital and other 502 healthy adult blood donors were selected. anti-sars antibodies were determined by anti-sars specific antibody detection kit and elisa method. the resu ...200415157337
following the rule: formation of the 6-helix bundle of the fusion core from severe acute respiratory syndrome coronavirus spike protein and identification of potent peptide inhibitors.severe acute respiratory syndrome (sars) coronavirus (sars-cov) is a newly identified member of family coronaviridae. coronavirus envelope spike protein s is a class i viral fusion protein which is characterized by the existence of two heptad repeat regions (hr1 and hr2) (forming a complex called fusion core). here we report that by using in vitro bio-engineering techniques, sars-cov hr1 and hr2 bind to each other and form a typical 6-helix bundle. the hr2, either as a synthetic peptide or as a ...200415158473
viral shedding patterns of coronavirus in patients with probable severe acute respiratory syndrome.severe acute respiratory syndrome (sars) is thought to be caused by a novel coronavirus, sars-associated coronavirus. we studied viral shedding of sars coronavirus to improve diagnosis and infection control. reverse-transcriptase pcr was done on 2134 specimens of different types. 355 (45%) specimens of nasopharyngeal aspirates and 150 (28%) of faeces were positive for sars coronavirus rna. positive rates peaked at 6-11 days after onset of illness for nasopharyngeal aspirates (87 of 149 [58%], to ...200415158632
[sars, pandemic influenza, avian influenza: quest for missing link]. 200415160886
bioinformatics analysis of sars coronavirus genome polymorphism.we have compared 38 isolates of the sars-cov complete genome. the main goal was twofold: first, to analyze and compare nucleotide sequences and to identify positions of single nucleotide polymorphism (snp), insertions and deletions, and second, to group them according to sequence similarity, eventually pointing to phylogeny of sars-cov isolates. the comparison is based on genome polymorphism such as insertions or deletions and the number and positions of snps.200415161495
glycan arrays lead to the discovery of autoimmunogenic activity of sars-cov.using carbohydrate microarrays, we characterized the carbohydrate binding activity of sars-cov neutralizing antibodies elicited by an inactivated sars-cov vaccine. in these antibodies, we detected undesired autoantibody reactivity specific for the carbohydrate moieties of an abundant human serum glycoprotein asialo-orosomucoid (asor). this observation provides important clues for the selection of specific immunologic probes to examine whether sars-cov expresses antigenic structures that mimic th ...200415161967
structural characterization of the fusion-active complex of severe acute respiratory syndrome (sars) coronavirus.the causative agent of a recent outbreak of an atypical pneumonia, known as severe acute respiratory syndrome (sars), has been identified as a coronavirus (cov) not belonging to any of the previously identified groups. fusion of coronaviruses with the host cell is mediated by the envelope spike protein. two regions within the spike protein of sars-cov have been identified, showing a high degree of sequence conservation with the other cov, which are characterized by the presence of heptad repeats ...200415161975
cloning, sequencing, expression, and purification of sars-associated coronavirus nucleocapsid protein for serodiagnosis of sars.a novel coronavirus has been associated with a worldwide outbreak of atypical pneumonia referred to as severe acute respiratory syndrome (sars-cov). sars-cov nucleocapsid (n) protein has been cloned sequenced and expressed in escherichia coli strain. purified n protein was used to measure the sars-cov specific igg antibodies from 16 sars-cov infected patients' sera and from 131 control subjects using elisa assay. specific antibody responses to the purified recombinant n protein after 10, 20, and ...200415163419
s protein of severe acute respiratory syndrome-associated coronavirus mediates entry into hepatoma cell lines and is targeted by neutralizing antibodies in infected patients.the severe acute respiratory syndrome-associated coronavirus (sars-cov) causes severe pneumonia with a fatal outcome in approximately 10% of patients. sars-cov is not closely related to other coronaviruses but shares a similar genome organization. entry of coronaviruses into target cells is mediated by the viral s protein. we functionally analyzed sars-cov s using pseudotyped lentiviral particles (pseudotypes). the sars-cov s protein was found to be expressed at the cell surface upon transient t ...200415163706
ace2: from vasopeptidase to sars virus receptor.the zinc metallopeptidase angiotensin-converting enzyme 2 (ace2) is the only known human homologue of the key regulator of blood pressure angiotensin-converting enzyme (ace). since its discovery in 2000, ace2 has been implicated in heart function, hypertension and diabetes, with its effects being mediated, in part, through its ability to convert angiotensin ii to angiotensin-(1-7). unexpectedly, ace2 also serves as the cellular entry point for the severe acute respiratory syndrome (sars) virus a ...200415165741
rapid identification of coronavirus replicase inhibitors using a selectable replicon rna.a previously unknown coronavirus (cov) is the aetiological agent causing severe acute respiratory syndrome (sars), for which an effective antiviral treatment is urgently needed. to enable the rapid and biosafe identification of coronavirus replicase inhibitors, we have generated a non-cytopathic, selectable replicon rna (based on human cov 229e) that can be stably maintained in eukaryotic cells. most importantly, the replicon rna mediates reporter gene expression as a marker for coronavirus repl ...200415166457
sars coronavirus induces apoptosis in vero e6 cells.severe acute respiratory syndrome (sars) is an emerging infectious disease. its etiological agent has been convincingly identified as a new member of family coronaviridae (sars-cov). it causes serious damage to the respiratory system yet the mechanism is not clear. infection-induced apoptosis or necrosis is suspected but no direct evidence for this yet exists. to date, vero e6 cells are the only cell line that could be used to replicate the virus with obvious cpe (cytopathic effect) in vitro. it ...200415170624
the life cycle of sars coronavirus in vero e6 cells.the aim of the study was to establish the life cycle of severe acute respiratory syndrome-associated coronavirus (sars cov) in host cells and determine the pathogenesis of sars. vero e6 cells (african green monkey kidney cells) were inoculated with sars coronavirus for 3, 7, 24, 48, and 72 hr, respectively, and were observed under electron microscope. it was found that the sars coronavirus entered the cells through membrane fusion instead of endocytosis, and then the nucleocapsids assembled in t ...200415170625
the life cycle of sars coronavirus in vero e6 cells.the aim of the study was to establish the life cycle of severe acute respiratory syndrome-associated coronavirus (sars cov) in host cells and determine the pathogenesis of sars. vero e6 cells (african green monkey kidney cells) were inoculated with sars coronavirus for 3, 7, 24, 48, and 72 hr, respectively, and were observed under electron microscope. it was found that the sars coronavirus entered the cells through membrane fusion instead of endocytosis, and then the nucleocapsids assembled in t ...200415170625
evaluation of antibody responses against sars coronaviral nucleocapsid or spike proteins by immunoblotting or elisa.severe acute respiratory syndrome (sars)-cov is a newly emerging virus that causes sars with high mortality rate in infected people. to study the humoral responses against sars-cov, we evaluated nucleocapsid (n) and spike (s) proteins-specific antibodies in patients' sera by western blotting and enzyme-linked immunosorbent assay (elisa). recombinant n and s proteins of sars-cov were purified from transformed e. coli. serum specimens from 40 sars-cov-infected patients in the convalescent phase we ...200415170626
[targets and studies on anti-sars drugs]. 200415171664
prevalence of non-pneumonic infections with sars-correlated virus. 200415172784
prevalence of non-pneumonic infections with sars-correlated virus. 200415172785
prevalence of non-pneumonic infections with sars-correlated virus. 200415172786
prevalence of non-pneumonic infections with sars-correlated virus. 200415172787
unpredictable patterns of viral respiratory disease in children. 200415173514
at the epicenter of severe acute respiratory syndrome. 200415173706
[development and evaluation of the kit for detection of sars-associated coronavirus rna].to develop a diagnostic kit for detection of sars (severe acute respiratory syndrome)-related coronavirus rna based on reverse transcription and polymerase chain reaction and to estimate its specificity and sensitivity.200415174316
[development and evaluation of the kit for detection of sars-associated coronavirus rna].to develop a diagnostic kit for detection of sars (severe acute respiratory syndrome)-related coronavirus rna based on reverse transcription and polymerase chain reaction and to estimate its specificity and sensitivity.200415174316
role of interferons in the treatment of severe acute respiratory syndrome.severe acute respiratory syndrome (sars) is caused by the sars coronavirus (scv). the disease appeared in the guandong province of southern china in 2002. the epidemic affected > 8422 patients and caused 908 deaths in 29 countries on 5 continents. several treatment modalities were tried with limited success to treat sars and a variety of experimental drugs are under development. type i interferons (ifns-alpha/beta) were suggested as potential candidates to treat sars. several animal and human co ...200415174965
serial analysis of plasma proteomic signatures in pediatric patients with severe acute respiratory syndrome and correlation with viral load. 200415178653
coronavirus 3clpro proteinase cleavage sites: possible relevance to sars virus pathology.despite the passing of more than a year since the first outbreak of severe acute respiratory syndrome (sars), efficient counter-measures are still few and many believe that reappearance of sars, or a similar disease caused by a coronavirus, is not unlikely. for other virus families like the picornaviruses it is known that pathology is related to proteolytic cleavage of host proteins by viral proteinases. furthermore, several studies indicate that virus proliferation can be arrested using specifi ...200415180906
attenuation of sars coronavirus by a short hairpin rna expression plasmid targeting rna-dependent rna polymerase.severe acute respiratory syndrome (sars) is a highly contagious and sometimes a lethal disease, which spread over five continents in 2002-2003. laboratory analysis showed that the etiologic agent for sars is a new type of coronavirus. currently, there is no specific treatment for this disease. rna interference (rnai) is a recently discovered antiviral mechanism in plant and animal cells that induces a specific degradation of double-stranded rna. here, we provide evidences that rnai targeting at ...200415183056
suppression of sars-cov entry by peptides corresponding to heptad regions on spike glycoprotein.heptad repeat regions (hr1 and hr2) are highly conserved sequences located in the glycoproteins of enveloped viruses. they form a six-helix bundle structure and are important in the process of virus fusion. peptides derived from the hr regions of some viruses have been shown to inhibit the entry of these viruses. sars-cov was also predicted to have hr1 and hr2 regions in the s2 protein. based on this prediction, we designed 25 peptides and screened them using a hiv-luc/sars pseudotyped virus ass ...200415184046
identification of two antigenic epitopes on sars-cov spike protein.the spike (s) protein of severe acute respiratory syndrome-coronavirus (sars-cov) is a major virion structural protein. it plays an important role in interaction with receptor and inducing neutralizing antibodies. in the study, six tentative antigenic epitopes (s1 s2 s3 s4 s5 s6) of the spike protein of sars-cov were predicted by bio-informatics analysis, and a multi-epitope chimeric gene of s1-s2-s3-s4-s5-s6 was synthesized and fused to downstream gst gene in pgex-6p-1. the western blotting dem ...200415184071
response of the clinical microbiology laboratory to emerging (new) and reemerging infectious diseases. 200415184405
sensitive and specific monoclonal antibody-based capture enzyme immunoassay for detection of nucleocapsid antigen in sera from patients with severe acute respiratory syndrome.a rapid antigen test for the diagnosis of severe acute respiratory syndrome (sars) is essential for control of this disease at the point of management. the nucleocapsid (n) protein of sars-associated coronavirus (sars-cov) is abundantly expressed in infected-cell culture filtrate as demonstrable by western blotting using convalescent-phase sera from patients with sars. we used monoclonal antibodies specifically directed against n protein to establish a sensitive antigen capture sandwich enzyme-l ...200415184444
high-efficiency detection of severe acute respiratory syndrome virus genetic material.a taqman amplicon targeting the nucleocapsid gene of severe acute respiratory syndrome coronavirus (sars-cov) is 5 log(10) times more sensitive for sars-cov target rna extracted from infected cells and 2.79 log(10) times more sensitive for rna extracted from patient material of the index case in frankfurt than an amplicon targeting the polymerase gene.200415184466
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