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combining clinical and epidemiologic features for early recognition of sars.early recognition and rapid initiation of infection control precautions are currently the most important strategies for controlling severe acute respiratory syndrome (sars). no rapid diagnostic tests currently exist that can rule out sars among patients with febrile respiratory illnesses. clinical features alone cannot with certainty distinguish sars from other respiratory illnesses rapidly enough to inform early management decisions. a balanced approach to screening that allows early recognitio ...200415030706
possible central nervous system infection by sars coronavirus.on day 22 of illness, generalized tonic-clonic convulsion developed in a 32-year-old woman with severe acute respiratory syndrome (sars). cerebrospinal fluid tested positive for sars coronavirus (sars-cov) by reverse transcriptase-polymerase chain reaction. sars-cov may have caused an infection in the central nervous system in this patient.200415030709
sars and pregnancy: a case report.we report a laboratory-confirmed case of severe acute respiratory syndrome (sars) in a pregnant woman. although the patient had respiratory failure, a healthy infant was subsequently delivered, and the mother is now well. there was no evidence of viral shedding at delivery. antibodies to sars virus were detected in cord blood and breast milk.200415030710
atypical sars and escherichia coli bacteremia.we describe a patient with severe acute respiratory syndrome (sars) whose clinical symptoms were masked by escherichia coli bacteremia. sars developed in a cluster of healthcare workers who had contact with this patient. sars was diagnosed when a chest infiltrate developed and when the patient's brother was hospitalized with acute respiratory failure. we highlight problems in atypical cases and offer infection control suggestions.200415030711
relative rates of non-pneumonic sars coronavirus infection and sars coronavirus pneumonia.although the genome of severe acute respiratory syndrome coronavirus (sars-cov) has been sequenced and a possible animal reservoir identified, seroprevalence studies and mass screening for detection of subclinical and non-pneumonic infections are still lacking.200415031027
serology of severe acute respiratory syndrome: implications for surveillance and outcome.severe acute respiratory syndrome (sars) is a novel infectious disease. no information is currently available on host-specific immunity against the sars coronavirus (cov), and detailed characteristics of the epidemiology of sars cov infection have not been identified.200415031782
severe acute respiratory syndrome-related coronavirus is inhibited by interferon- alpha.current treatment schemes for severe acute respiratory syndrome (sars) include broad-spectrum antibiotics, glucocorticoids, and ribavirin. we evaluated the susceptibility of the sars-related coronavirus (sars cov) to ribavirin and interferon (ifn)- alpha in vitro by use of cytopathic effect, plaque assay, and immunoblot analysis. ribavirin did not inhibit viral growth at concentrations attainable in human serum. in contrast, ifn- alpha showed an in vitro inhibitory effect starting at concentrati ...200415031783
severe acute respiratory syndrome-related coronavirus is inhibited by interferon- alpha.current treatment schemes for severe acute respiratory syndrome (sars) include broad-spectrum antibiotics, glucocorticoids, and ribavirin. we evaluated the susceptibility of the sars-related coronavirus (sars cov) to ribavirin and interferon (ifn)- alpha in vitro by use of cytopathic effect, plaque assay, and immunoblot analysis. ribavirin did not inhibit viral growth at concentrations attainable in human serum. in contrast, ifn- alpha showed an in vitro inhibitory effect starting at concentrati ...200415031783
protein structure prediction in structure based drug design.the human genome and other genome sequencing projects have generated huge amounts of protein sequence information. recently, a structural genomics project that aims to determine at least one representative three-dimensional structure from every protein family experimentally has been started. homology modeling will play an essential role in structure based drug design such as in silico screening; because based on these representative structures the three-dimensional structures of the remaining pr ...200415032603
sars--beginning to understand a new virus.the 114-day epidemic of the severe acute respiratory syndrome (sars) swept 29 countries, affected a reported 8,098 people, left 774 patients dead and almost paralyzed the asian economy. aggressive quarantine measures, possibly aided by rising summer temperatures, successfully terminated the first eruption of sars and provided at least a temporal break, which allows us to consolidate what we have learned so far and plan for the future. here, we review the genomics of the sars coronavirus (sars-co ...200315035025
dissection study on the severe acute respiratory syndrome 3c-like protease reveals the critical role of the extra domain in dimerization of the enzyme: defining the extra domain as a new target for design of highly specific protease inhibitors.the severe acute respiratory syndrome (sars) 3c-like protease consists of two distinct folds, namely the n-terminal chymotrypsin fold containing the domains i and ii hosting the complete catalytic machinery and the c-terminal extra helical domain iii unique for the coronavirus 3cl proteases. previously the functional role of this extra domain has been completely unknown, and it was believed that the coronavirus 3cl proteases share the same enzymatic mechanism with picornavirus 3c proteases, whic ...200415037623
analysis of synonymous codon usage in sars coronavirus and other viruses in the nidovirales.in this study, we calculated the codon usage bias in severe acute respiratory syndrome coronavirus (sarscov) and performed a comparative analysis of synonymous codon usage patterns in sarscov and 10 other evolutionary related viruses in the nidovirales. although there is a significant variation in codon usage bias among different sarscov genes, codon usage bias in sarscov is a little slight, which is mainly determined by the base compositions on the third codon position. by comparing synonymous ...200415041183
[epidemiological investigation of nosocomial infection of sars in medical staff of a hospital].to investigate the epidemiological features of nosocomial infection of severe acute respiratory syndrome (sars) in the medical staff of a hospital.200415041564
[severe acute respiratory syndrome: a singular epidemic of viral pneumonia].infectious agent: the severe acute respiratory syndrome (sars) is a febrile pneumonia initially observed in china at the end of 2002. the infectious agent has rapidly been identified as a new coronavirus, baptised sars-associated coronavirus (cov-sars). transmission is inter-human, via respiratory particles mainly. clinical presentation and treatment: the clinical presentation is highly variable, from a mild fever to an acute respiratory distress syndrome. there is no specific treatment. ribavir ...200415041887
sars virus returns to china as scientists race to find effective vaccine. 200415042239
severe acute respiratory syndrome: scientific and anecdotal evidence for drug treatment.severe acute respiratory syndrome (sars), caused by a highly infectious novel coronavirus (cov), predominantly presents with severe pneumonitis leading to respiratory failure and death in approximately 10% of victims. most cases present, after an incubation of 2 to 11 days, with fever and chills, which are followed by dry cough and dyspnea before the onset of respiratory failure. the management of sars is controversial, largely due to the lack of data from controlled trials, which were logistica ...200415043392
viral attacks on the blood supply: the impact of severe acute respiratory syndrome in beijing. 200415043559
nat screening of blood donors for severe acute respiratory syndrome coronavirus can potentially prevent transfusion associated transmissions.the severe acute respiratory syndrome (sars) was first described in february 2003. close contact with symptomatic patients appears to be the main route of transmission, whereas blood transfusion transmission could not be ruled out.200415043560
coronavirus outbreak in cheetahs: lessons for sars. 200415043830
interaction between heptad repeat 1 and 2 regions in spike protein of sars-associated coronavirus: implications for virus fusogenic mechanism and identification of fusion inhibitors.studies on the fusion-inhibitory peptides derived from the heptad repeat 1 and 2 (hr1 and hr2) regions of the hiv-1 envelope glycoprotein gp41 provided crucial information on the viral fusogenic mechanism. we used a similar approach to study the fusogenic mechanism of severe-acute-respiratory-syndrome-associated coronavirus (sars-cov).200415043961
synthetic peptide studies on the severe acute respiratory syndrome (sars) coronavirus spike glycoprotein: perspective for sars vaccine development.the s (spike) protein of the etiologic coronavirus (cov) agent of severe acute respiratory syndrome (sars) plays a central role in mediating viral infection via receptor binding and membrane fusion between the virion and the host cell. we focused on using synthetic peptides for developing antibodies against sars-cov, which aimed to block viral invasion by eliciting an immune response specific to the native sars-cov s protein.200415044316
sars-associated coronavirus quasispecies in individual patients. 200415044654
mutational patterns correlate with genome organization in sars and other coronaviruses.focused efforts by several international laboratories have resulted in the sequencing of the genome of the causative agent of severe acute respiratory syndrome (sars), novel coronavirus sars-cov, in record time. using cumulative skew diagrams, i found tht mutational patterns in the sars-cov genome were strikingly different from other coronaviruses in terms of mutation rates, although they were in general agreement with the model of the coronavirus lifecycle. these findings might be relevant for ...200415049309
one-tube nested rt-pcr enabled by using a plastic film and its application for the rapid detection of sars-virus.a general strategy based on the use of a plastic film that allows reverse transcription and nested-pcr in a single closed-tube has been developed. the reaction mixture for the second pcr amplification is quarantined in the cap of the reaction tube during the first round amplification by a piece of plastic film, and later introduced into the pcr amplicons from the first round reaction by centrifugation without opening the reaction tube. the main advantages of our method are its high sensitivity, ...200415049359
rapid detection of the severe acute respiratory syndrome (sars) coronavirus by a loop-mediated isothermal amplification assay. 200415054079
antigenicity analysis of different regions of the severe acute respiratory syndrome coronavirus nucleocapsid protein.the widespread threat of severe acute respiratory syndrome (sars) to human health has made urgent the development of fast and accurate analytical methods for its early diagnosis and a safe and efficient antiviral vaccine for preventive use. for this purpose, we investigated the antigenicity of different regions of the sars coronavirus (sars-cov) nucleocapsid (n) protein.200415054081
bioterrorism and emerging infectious disease - antimicrobials, therapeutics and immune-modulators. sars coronavirus.the purpose of this meeting was to provide a forum for expert presentations and discussion about the threats of bioterrorism and emerging infectious diseases, and to address the issues relating to epidemics, prevention of infection and treatment of some of these emerging infectious diseases classified as potential agents of bioterror. included in the talks were state-of-the-art presentations about infectious clone technology and recombinant viruses, pathogen and receptor interactions at the cell ...200415057645
phylogenomics and bioinformatics of sars-cov. 200415058277
[an epidemiologic investigation on infection with severe acute respiratory syndrome coronavirus in wild animals traders in guangzhou].to investigate status of infection with severe acute respiratory syndrome coronovirus (sars-cov) in traders of wild animals wholesale markets in guangzhou.200415061910
[detection for severe acute respiratory syndrome (sars) coronavirus rna in stool of sars patients].to investigate excretion of severe acute respiratory syndrome coronavirus rna (sars-cov) in stool of sars patients.200415061913
procalcitonin in severe acute respiratory syndrome (sars).the role of procalcitonin (pct) in severe acute respiratory syndrome (sars) has not been highlighted so far. we described retrospectively eight cases of sepsis from pneumonia of various microbiological aetiologies including two due to sars, compared their pct concentrations and provided further descriptors of sars as a viral pneumonia.200415066330
performance and cost evaluation of one commercial and six in-house conventional and real-time reverse transcription-pcr assays for detection of severe acute respiratory syndrome coronavirus.we evaluated seven reverse transcription-pcr (rt-pcr) assays, including six in-house assays and one commercial assay for the detection of severe acute respiratory syndrome coronavirus (sars-cov) rna in clinical specimens. rt-pcr assays targeted different genomic regions and included three conventional assays (one nested and two non-nested) run on a conventional heat block and four real-time assays performed in a lightcycler (lc; roche diagnostics). all in-house assays were optimized for assay pa ...200415070991
immunological characterization of the spike protein of the severe acute respiratory syndrome coronavirus.severe acute respiratory syndrome (sars) is a novel infectious disease caused by the sars-associated coronavirus (sars-cov). there are four major structural proteins in the sars-cov, including the nucleocapsid, spike, membrane, and small envelope proteins. in this study, two sets of truncated fragments of spike protein were generated, the first were approximately 210-bp nonoverlapping fragments and the second were overlapping segments of 750 to 900 bp. from these 23 fragments, we identified a fr ...200415071006
boosting the sensitivity of real-time polymerase-chain-reaction testing for sars. 200415071137
factors that make an infectious disease outbreak controllable.the aim of this study is to identify general properties of emerging infectious agents that determine the likely success of two simple public health measures in controlling outbreaks, namely (i) isolating symptomatic individuals and (ii) tracing and quarantining their contacts. because these measures depend on the recognition of specific disease symptoms, we investigate the relative timing of infectiousness and the appearance of symptoms by using a mathematical model. we show that the success of ...200415071187
[sars coronavirus]. 200315071959
a previously undescribed coronavirus associated with respiratory disease in humans.the etiology of acute respiratory tract illnesses is sometimes unclear due to limitations of diagnostic tests or the existence of as-yet-unidentified pathogens. here we describe the identification and characterization of a not previously recognized coronavirus obtained from an 8-mo-old boy suffering from pneumonia. this coronavirus replicated efficiently in tertiary monkey kidney cells and vero cells, in contrast to human coronaviruses (hcov) 229e and oc43. the entire cdna genome sequence of the ...200415073334
inhibition of severe acute respiratory syndrome-associated coronavirus (sarscov) by calpain inhibitors and beta-d-n4-hydroxycytidine.we evaluated two types of compounds for efficacy in inhibiting sarscov replication in vitro: calpain inhibitors (a class of cellular cysteine proteinases) and a number of nucleoside analogues. cytopathic effect reduction assays visually determined with spectrophotometric verification by neutral red (nr) uptake assay were used to evaluate cytotoxicity and antiviral potency of the compounds. significantly inhibitory compounds were then evaluated in virus yield reduction assays. two calpain inhibit ...200415074711
coronavirus infection in an aids patient. 200415075525
3c-like proteinase from sars coronavirus catalyzes substrate hydrolysis by a general base mechanism.sars 3c-like proteinase has been proposed to be a key enzyme for drug design against sars. lack of a suitable assay has been a major hindrance for enzyme kinetic studies and a large-scale inhibitor screen for sars 3cl proteinase. since sars 3cl proteinase belongs to the cysteine protease family (family c3 in clan cb) with a chymotrypsin fold, it is important to understand the catalytic mechanism of sars 3cl proteinase to determine whether the proteolysis proceeds through a general base catalysis ...200415078103
amino acids 270 to 510 of the severe acute respiratory syndrome coronavirus spike protein are required for interaction with receptor.a novel coronavirus, severe acute respiratory syndrome coronavirus (sars-cov), has recently been identified as the causative agent of severe acute respiratory syndrome (sars). sars-cov appears similar to other coronaviruses in both virion structure and genome organization. it is known for other coronaviruses that the spike (s) glycoprotein is required for both viral attachment to permissive cells and for fusion of the viral envelope with the host cell membrane. here we describe the construction ...200415078936
generation and characterization of dna vaccines targeting the nucleocapsid protein of severe acute respiratory syndrome coronavirus.severe acute respiratory syndrome (sars) is a serious threat to public health and the economy on a global scale. the sars coronavirus (sars-cov) has been identified as the etiological agent for sars. thus, vaccination against sars-cov may represent an effective approach to controlling sars. dna vaccines are an attractive approach for sars vaccine development, as they offer many advantages over conventional vaccines, including stability, simplicity, and safety. our investigators have previously s ...200415078946
the involvement of natural killer cells in the pathogenesis of severe acute respiratory syndrome.by using peripheral blood samples from 221 cases of severe acute respiratory syndrome (sars), 34 of mycoplasma pneumoniae infection, and 44 healthy adults, we measured the total number of natural killer (nk) and cd158b+ nk cells (cd158b+ nk) using flow cytometric analysis and calculated the percentage of cd158b+ nk cells. the total number of nk and cd158b+ nk cells and the percentage of cd158b+ nk cells were significantly lower in patients with sars than in those with m. pneumoniae infection (p ...200415080302
detection of severe acute respiratory syndrome-associated coronavirus in pneumocytes of the lung.previous reports have indicated that patients with severe acute respiratory syndrome (sars)-associated coronavirus infection could develop atypical pneumonia with fulminant pulmonary edema. however, the target cells of sars viral infection have not been characterized in detail. we report the pathologic findings of the lung in 3 cases of sars. chest radiographs at 2 to 3 weeks of infection revealed an atypical pneumonia with pulmonary consolidation, a clinical characteristic of sars infection. th ...200415080310
exploring the binding mechanism of the main proteinase in sars-associated coronavirus and its implication to anti-sars drug design.the main proteinase of sars-associated coronavirus (sars-cov) plays an important role in viral transcription and replication, and is an attractive target for anti-sars drug development. the important thing is to understand its binding mechanism with possible ligands. in this study, we investigated possible noncanonical interactions, potential inhibitors, and binding pockets in the main proteinase of sars-cov based on its recently determined crystal structure. these findings provide a wide clue t ...200415080921
induction of sars-nucleoprotein-specific immune response by use of dna vaccine.induction of effective cytotoxic t lymphocyte (ctl) and/or a specific antibody against conserved viral proteins may be essential to the development of a safe and effective severe acute respiratory syndrome coronavirus (sars-cov) vaccine. dna vaccination represents a new strategy for induction of humoral and cellular immune response. to determine the ability of sars-cov nucleoprotein (n protein) to induce antiviral immunity, in this report, we established a stable c2c12 line expressing sars-cov n ...200415081618
are there characteristics of infectious diseases that raise special ethical issues?this paper examines the characteristics of infectious diseases that raise special medical and social ethical issues, and explores ways of integrating both current bioethical and classical public health ethics concerns. many of the ethical issues raised by infectious diseases are related to these diseases' powerful ability to engender fear in individuals and panic in populations. we address the association of some infectious diseases with high morbidity and mortality rates, the sense that infecti ...200415086371
primary characterization of sars coronavirus strain frankfurt 1. 200415088406
the nucleocapsid protein of the sars coronavirus is capable of self-association through a c-terminal 209 amino acid interaction domain.severe acute respiratory syndrome (sars) coronavirus (sars-cov) caused a severe outbreak in several regions of the world in 2003. the virus is a novel coronavirus isolated from patients exhibiting atypical pneumonia and may have originated from wild animals such as civet cats in southern china. the genome of sars-cov is a positive-sense, single-stranded rna whose sequence is distantly related to all known coronaviruses that infect humans and animals. like other known coronaviruses, sars-cov is a ...200415094372
[sars]. 200415095764
severe acute respiratory syndrome.severe acute respiratory syndrome (sars) is a new respiratory illness due to a novel coronavirus called sars-cov. cases of sars were first identified from guangdong province in southern china in november 2002. over the next several months, international travel allowed for the rapid spread of >8,000 cases over three continents. the economic and psychological impact of this mysterious illness was profound. in order to better educate the public about this emerging infectious disease, we describe th ...200415095827
the spectrum of severe acute respiratory syndrome-associated coronavirus infection.whether subclinical or atypical presentations of severe acute respiratory syndrome (sars) occur and whether clinical judgment is accurate in detecting sars are unknown. objectives: to describe the spectrum of sars coronavirus infection in a large outbreak and to compare diagnoses based on clinical judgment with the sars coronavirus test.200415096332
summaries for patients. do some patients with sars have mild disease? 200415096361
antibody response and viraemia during the course of severe acute respiratory syndrome (sars)-associated coronavirus infection.to understand the time-course of viraemia and antibody responses to severe acute respiratory syndrome-associated coronavirus (sars-cov), rt-pcr and elisa were used to assay 376 blood samples from 135 sars patients at various stages of the illness, including samples from patients who were in their early convalescent phase. the results showed that igm antibodies decreased and became undetectable 11 weeks into the recovery phase. igg antibodies, however, remained detectable for a period beyond 11 w ...200415096554
severe acute respiratory syndrome coronavirus spike protein expressed by attenuated vaccinia virus protectively immunizes mice.the spike protein (s), a membrane component of severe acute respiratory syndrome coronavirus (sars-cov) is anticipated to be an important component of candidate vaccines. we constructed recombinant forms of the highly attenuated modified vaccinia virus ankara (mva) containing the gene encoding full-length sars-cov s with and without a c-terminal epitope tag called mva/s-ha and mva/s, respectively. cells infected with mva/sor mva/s-ha synthesized a 200-kda protein, which was recognized by antibod ...200415096611
evidence of airborne transmission of the severe acute respiratory syndrome virus.there is uncertainty about the mode of transmission of the severe acute respiratory syndrome (sars) virus. we analyzed the temporal and spatial distributions of cases in a large community outbreak of sars in hong kong and examined the correlation of these data with the three-dimensional spread of a virus-laden aerosol plume that was modeled using studies of airflow dynamics.200415102999
laboratory-acquired severe acute respiratory syndrome. 200415103000
sars ctl vaccine candidates; hla supertype-, genome-wide scanning and biochemical validation.an effective severe acute respiratory syndrome (sars) vaccine is likely to include components that can induce specific cytotoxic t-lymphocyte (ctl) responses. the specificities of such responses are governed by human leukocyte antigen (hla)-restricted presentation of sars-derived peptide epitopes. exact knowledge of how the immune system handles protein antigens would allow for the identification of such linear sequences directly from genomic/proteomic sequence information (lauemoller et al., re ...200415104671
[severe acute respiratory syndrome]. 200415108450
identification of novel inhibitors of the sars coronavirus main protease 3clpro.sars (severe acute respiratory syndrome) is caused by a newly discovered coronavirus. a key enzyme for the maturation of this virus and, therefore, a target for drug development is the main protease 3cl(pro) (also termed sars-cov 3cl(pro)). we have cloned and expressed in escherichia coli the full-length sars-cov 3cl(pro) as well as a truncated form containing only the catalytic domains. the recombinant proteins have been characterized enzymatically using a fluorescently labeled substrate; their ...200415109248
coronaviridae and sars-associated coronavirus strain hsr1.during the recent severe acute respiratory (sars) outbreak, the etiologic agent was identified as a new coronavirus (cov). we have isolated a sars-associated cov (sars-cov) strain by injecting vero cells with a sputum specimen from an italian patient affected by a severe pneumonia; the patient traveled from vietnam to italy in march 2003. ultrastructural analysis of infected vero cells showed the virions within cell vesicles and around the cell membrane. the full-length viral genome sequence was ...200415109406
development of taqman rt-nested pcr system for clinical sars-cov detection.severe acute respiratory syndrome (sars) is an acute newly emerged infectious respiratory illness. the etiologic agent of sars was named 'sars-associated coronavirus' (sars-cov) that can be detected with reverse transcription-polymerase chain reaction (rt-pcr) assays. in this study, 12 sets of nested primers covering the sars-cov genome have been screened and showed sufficient sensitivity to detect sars-cov in rna isolated from virus cultured in vero 6 cells. to optimize further the reaction con ...200415109816
microbicides and the environmental control of nosocomial viral infections.viruses are important causes of acute and chronic diseases in humans. newer viruses are still being discovered and those that are already known are being incriminated in the aetiology of clinical conditions with hitherto unknown causes. apart from frequently causing infections in the general community, many types of viruses are also significant nosocomial pathogens. while it is generally agreed that we underestimate the proportion of nosocomial infections that are viral, due to a lack of routine ...200415110126
old drugs as lead compounds for a new disease? binding analysis of sars coronavirus main proteinase with hiv, psychotic and parasite drugs.the sars-associated coronavirus (sars-cov) main proteinase is a key enzyme in viral polyprotein processing. to allow structure-based design of drugs directed at sars-cov main proteinase, we predicted its binding pockets and affinities with existing hiv, psychotic and parasite drugs (lopinavir, ritonavir, niclosamide and promazine), which show signs of inhibiting the replication of sars-cov. our results suggest that these drugs and another two hiv inhibitors (pnu and uc2) could be used as templat ...200415110833
severe acute respiratory syndrome: report of treatment and outcome after a major outbreak.the outcome is reported of a prospective uncontrolled study based on a stepwise treatment protocol during an outbreak of severe acute respiratory syndrome (sars) in hong kong.200415115870
monophyletic relationship between severe acute respiratory syndrome coronavirus and group 2 coronaviruses.although primary genomic analysis has revealed that severe acute respiratory syndrome coronavirus (sars cov) is a new type of coronavirus, the different protein trees published in previous reports have provided no conclusive evidence indicating the phylogenetic position of sars cov. to clarify the phylogenetic relationship between sars cov and other coronaviruses, we compiled a large data set composed of 7 concatenated protein sequences and performed comprehensive analyses, using the maximum-lik ...200415116304
stability and inactivation of sars coronavirus.the sars-coronavirus (sars-cov) is a newly emerged, highly pathogenic agent that caused over 8,000 human infections with nearly 800 deaths between november 2002 and september 2003. while direct person-to-person transmission via respiratory droplets accounted for most cases, other modes have not been ruled out. faecal shedding is common and prolonged and has caused an outbreak in hong kong. we studied the stability of sars-cov under different conditions, both in suspension and dried on surfaces, ...200515118911
[winter viruses]. 200415119334
prediction of amino acid pairs sensitive to mutations in the spike protein from sars related coronavirus.in this study, we analyzed the amino acid pairs affected by mutations in two spike proteins from human coronavirus strains 229e and oc43 by means of random analysis in order to gain some insight into the possible mutations in the spike protein from sars-cov. the results demonstrate that the randomly unpredictable amino acid pairs are more sensitive to the mutations. the larger is the difference between actual and predicted frequencies, the higher is the chance of mutation occurring. the effect i ...200315127935
[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
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