Publications

the nonstructural protein 8 (nsp8) of the sars coronavirus interacts with its orf6 accessory protein.	severe acute respiratory syndrome (sars) coronavirus (sars-cov) caused a severe outbreak in several regions of the world in 2003. the sars-cov genome is predicted to contain 14 functional open reading frames (orfs). the first orf (1a and 1b) encodes a large polyprotein that is cleaved into nonstructural proteins (nsp). the other orfs encode for four structural proteins (spike, membrane, nucleocapsid and envelope) as well as eight sars-cov-specific accessory proteins (3a, 3b, 6, 7a, 7b, 8a, 8b an ...	2007	17532020
up-regulation of il-6 and tnf-alpha induced by sars-coronavirus spike protein in murine macrophages via nf-kappab pathway.	the clinical picture of severe acute respiratory syndrome (sars) is characterized by an over-exuberant immune response with lung lymphomononuclear cells infilteration and proliferation that may account for tissue damage more than the direct effect of viral replication. to understand how cells response in the early stage of virus-host cell interaction, in this study, a purified recombinant s protein was studied for stimulating murine macrophages (raw264.7) to produce proinflammatory cytokines (il ...	2007	17532082
cleavage of spike protein of sars coronavirus by protease factor xa is associated with viral infectivity.	the spike (s) protein of sars coronavirus (sars-cov) has been known to recognize and bind to host receptors, whose conformational changes then facilitate fusion between the viral envelope and host cell membrane, leading to viral entry into target cells. however, other functions of sars-cov s protein such as proteolytic cleavage and its implications to viral infection are incompletely understood. in this study, we demonstrated that the infection of sars-cov and a pseudovirus bearing the s protein ...	2007	17533109
lack of support for an association between clec4m homozygosity and protection against sars coronavirus infection.		2007	17534354
lack of support for an association between clec4m homozygosity and protection against sars coronavirus infection.		2007	17534355
newcastle disease virus, a host range-restricted virus, as a vaccine vector for intranasal immunization against emerging pathogens.	the international outbreak of the severe acute respiratory syndrome-associated coronavirus (sars-cov) in 2002-2003 highlighted the need to develop pretested human vaccine vectors that can be used in a rapid response against newly emerging pathogens. we evaluated newcastle disease virus (ndv), an avian paramyxovirus that is highly attenuated in primates, as a topical respiratory vaccine vector with sars-cov as a test pathogen. complete recombinant ndv was engineered to express the sars-cov spike ...	2007	17535926
the association of rantes polymorphism with severe acute respiratory syndrome in hong kong and beijing chinese.	chemokines play important roles in inflammation and antiviral action. we examined whether polymorphisms of rantes, ip-10 and mig affect the susceptibility to and outcome of severe acute respiratory syndrome (sars).	2007	17540042
genomic analysis and geographic visualization of h5n1 and sars-cov.	emerging infectious diseases and organisms present critical issues of national security public health, and economic welfare. we still understand little about the zoonotic potential of many viruses. to this end, we are developing novel database tools to manage comparative genomic datasets. these tools add value because they allow us to summarize the direction, frequency and order of genomic changes. we will perform numerous real world tests with our tools with both avian influenza and coronavirus ...	2007	18694075
recent patents on treatment of severe acute respiratory syndrome (sars).	severe acute respiratory syndrome (sars) is an epidemic that spread worldwide in early 2003. the aetiological agent was originally defined as a novel coronavirus and later designated as the sars coronavirus (sars-cov), which appears similar to other coronaviruses in both virion structure and genome organization with a single-stranded, plus-sense rna. however, the epidemiology and pathogenesis of sars remain poorly understood and there is currently no effective treatment. to date, considerable re ...	2007	18221160
duration of antibody responses after severe acute respiratory syndrome.	among 176 patients who had had severe acute respiratory syndrome (sars), sars-specific antibodies were maintained for an average of 2 years, and significant reduction of immunoglobulin g-positive percentage and titers occurred in the third year. thus, sars patients might be susceptible to reinfection >or=3 years after initial exposure.	2007	18258008
an outbreak of human coronavirus oc43 infection and serological cross-reactivity with sars coronavirus.	in summer 2003, a respiratory outbreak was investigated in british columbia, during which nucleic acid tests and serology unexpectedly indicated reactivity for severe acute respiratory syndrome coronavirus (sars-cov).	2006	18382647
proteinase dysbalance in pathology: the neprilysin (nep) and angiotensin-converting enzyme (ace) families.	proteolytic enzymes constitute some 2% of the human genome and provide important therapeutic targets in many diseases. the identification of many novel proteases from genome sequencing programmes provides both qualitative and quantitative challenges to target identification and validation. some approaches to dealing with these questions and addressing functional correlates of proteolytic activity at the level of molecular cell biology are provided in this review focusing on two spheres of intere ...	2006	17543197
sars coronavirus anti-infectives.	severe acute respiratory syndrome (sars) emerged in late 2002 and was controlled in july 2003 by public health measures. its causative agent, sars coronavirus (sars-cov) jumped from an animal reservoir to humans and has the potential to re-emerge. following the sequencing of the genetic code and the deciphering of some of the functions of its proteins, including the cellular receptors and host proteins that participate in the life cycle of the virus, promising lead drugs and new uses of old drug ...	2006	18221155
antigenic and immunogenic characterization of recombinant baculovirus-expressed severe acute respiratory syndrome coronavirus spike protein: implication for vaccine design.	the spike (s) glycoprotein of severe acute respiratory syndrome coronavirus (sars-cov) mediates the receptor interaction and immune recognition and is considered a major target for vaccine design. however, its antigenic and immunogenic properties remain to be elucidated. in this study, we immunized mice with full-length s protein (fl-s) or its extracellular domain (ec-s) expressed by recombinant baculoviruses in insect cells. we found that the immunized mice developed high titers of anti-s antib ...	2006	16731915
endosomal proteolysis by cathepsins is necessary for murine coronavirus mouse hepatitis virus type 2 spike-mediated entry.	most strains of murine coronavirus mouse hepatitis virus (mhv) express a cleavable spike glycoprotein that mediates viral entry and ph-independent cell-cell fusion. the mhv type 2 (mhv-2) strain of murine coronavirus differs from other strains in that it expresses an uncleaved spike and cannot induce cell-cell fusion at neutral ph values. we show here that while infection of the prototype mhv-a59 strain is not sensitive to pretreatment with lysosomotropic agents, mhv-2 replication is significant ...	2006	16731916
ultrastructure and origin of membrane vesicles associated with the severe acute respiratory syndrome coronavirus replication complex.	the rna replication complexes of mammalian positive-stranded rna viruses are generally associated with (modified) intracellular membranes, a feature thought to be important for creating an environment suitable for viral rna synthesis, recruitment of host components, and possibly evasion of host defense mechanisms. here, using a panel of replicase-specific antisera, we have analyzed the earlier stages of severe acute respiratory syndrome coronavirus (sars-cov) infection in vero e6 cells, in parti ...	2006	16731931
delineation and modelling of a nucleolar retention signal in the coronavirus nucleocapsid protein.	unlike nuclear localization signals, there is no obvious consensus sequence for the targeting of proteins to the nucleolus. the nucleolus is a dynamic subnuclear structure which is crucial to the normal operation of the eukaryotic cell. studying nucleolar trafficking signals is problematic as many nucleolar retention signals (norss) are part of classical nuclear localization signals (nlss). in addition, there is no known consensus signal with which to inform a study. the avian infectious bronchi ...	2006	16734668
anti-rna virus activity of polyoxometalates.	the anti-rna virus activity of polyoxometalates (pom) is reviewed, with a special emphasis on the anti-respiratory virus activities. there are many causative agents of acute viral respiratory infections; and it is rather difficult to identify the relevant agent in a given case by rapid clinical means. during acute progress of infection before the definitive diagnosis is obtained physicians need to prescribe certain broad spectrum anti-viral drugs. a titanium containing polyoxotungstate, pm-523 e ...	2006	16737794
bats and human emerging diseases.		2006	16740197
expression and functional characterization of the putative protein 8b of the severe acute respiratory syndrome-associated coronavirus.	sars 8b is one of the putative accessory proteins of the severe acute respiratory syndrome-associated coronavirus (sars-cov) with unknown functions. in this study, the cellular localization and activity of this estimated 9.6 kda protein were examined. confocal microscopy results indicated that sars 8b is localized in both nucleus and cytoplasm of mammalian cells. functional study revealed that overexpression of sars 8b induced dna synthesis. coexpression of sars 8b and sars 6, a previously chara ...	2006	16753150
identification of effective sirna blocking the expression of sars viral envelope e and rdrp genes.	a cell-based assay was developed to screen small interference rna (sirna) to block the expression of two genes of the severe acute respiratory syndrome (sars) virus. these two genes encode rna-dependent rna polymerase (rdrp) and envelope e protein. the rdrp plays an essential role in viral rna replication where envelope e protein is involved in envelope formation and virus assembly. the rdrp and envelope e genes, based on published sequences, have been synthesized and cloned into mammalian expre ...	2006	16757801
isatin compounds as noncovalent sars coronavirus 3c-like protease inhibitors.	a series of isatin derivatives were synthesized and tested against sars cov 3c-like protease. substitutions at the n-1 and c-5 positions were examined to elucidate the differences in substrate binding sites of the rhinovirus 3c protease and sars cov 3c-like protease. compound 5f shows significant inhibition with an ic(50) of 0.37 microm. further study showed that, unlike the irreversible covalent binding of isatin derivatives to human rhinovirus 3c protease, the compounds tested in this study ar ...	2006	16759084
discovery of a novel family of sars-cov protease inhibitors by virtual screening and 3d-qsar studies.	the severe acute respiratory syndrome-associated coronavirus (sars-cov) 3c-like protease (3cl(pro) or m(pro)) is an attractive target for the development of anti-sars drugs because of its crucial role in the viral life cycle. in this study, a compound database was screened by the structure-based virtual screening approach to identify initial hits as inhibitors of sars-cov 3cl(pro). out of the 59,363 compounds docked, 93 were selected for the inhibition assay, and 21 showed inhibition against sar ...	2006	16759091
effect of various pyrimidines possessing the 1-[(2-hydroxy-1-(hydroxymethyl)ethoxy)methyl] moiety, able to mimic natural 2'-deoxyribose, on wild-type and mutant hepatitis b virus replication.	hepatitis b virus (hbv) is the most common cause of chronic liver disease worldwide. development of drug resistance against clinical anti-hbv drug lamivudine due to long-term use and rebound of viral dna after cessation of treatment has been a major setback of the current therapy. we have synthesized a series of pyrimidine nucleosides possessing a variety of substituents at the c-5 position, and a 1-[(2-hydroxy-1-(hydroxymethyl)ethoxy)methyl] flexible acyclic glycosyl moiety at the n-1 position, ...	2006	16759112
plasma glucose levels and diabetes are independent predictors for mortality and morbidity in patients with sars.	to investigate the relationships between a known history of diabetes and ambient fasting plasma glucose (fpg) levels with death and morbidity rates in patients with severe acute respiratory syndrome (sars).	2006	16759303
is there an ideal animal model for sars?	the outbreak of severe acute respiratory syndrome (sars) in 2003 was controlled by public health measures at a time when specific interventions such as antiviral drugs, vaccines and immunotherapy were not available. since then, several animal models have been developed for the study of sars and, although no model replicates the human disease in all aspects, the use of animal models for sars has led to the establishment of several important principles for vaccine and immunotherapy. consistency an ...	2006	16759866
interaction of severe acute respiratory syndrome-associated coronavirus with dendritic cells.	severe acute respiratory syndrome (sars) of humans is caused by a novel coronavirus of zoonotic origin termed sars-associated coronavirus (sars-cov). the virus induces severe injury of lung tissue, as well as lymphopenia and destruction of the architecture of lymphatic tissue by as-yet-unknown mechanisms. in this study, the interaction of sars-cov with dendritic cells (dcs), the key regulators of immune responses, was analysed. monocyte-derived dcs were infected with sars-cov and analysed for vi ...	2006	16760397
prevalence of subclinical infection and transmission of severe acute respiratory syndrome (sars) in a residential care home for the elderly.	to ascertain the prevalence of subclinical severe acute respiratory syndrome-coronavirus (sars-cov) infection and study the transmission of sars-cov in a local outbreak at a residential care home for the elderly.	2006	16760548
biophysical characterization of hrc peptide analogs interaction with heptad repeat regions of the sars-coronavirus spike fusion protein core.	the spike (s) protein of sars-coronavirus (sars-cov) mediates viral entry into host cells. it contains two heptad repeat regions, denoted hrn and hrc. we have identified the location of the two interacting hr regions that form the six-helix bundle (b. tripet, et al, j. biol. chem., 279: 20836-20849, 2004). in this study, hrc peptide (1150-1185) was chosen as the region to make structure-based substitutions to design a series of hrc analogs with increased hydrophobicity, helical propensity and el ...	2006	16765058
more mysteries of hiv and sars are revealed.		2006	16771611
identification of pulmonary oct-4+ stem/progenitor cells and demonstration of their susceptibility to sars coronavirus (sars-cov) infection in vitro.	in this study, we report a serum-free culture system for primary neonatal pulmonary cells that can support the growth of octamer-binding transcription factor 4+ (oct-4+) epithelial colonies with a surrounding mesenchymal stroma. in addition to oct-4, these cells also express other stem cell markers such as stage-specific embryonic antigen 1 (ssea-1), stem cell antigen 1 (sca-1), and clara cell secretion protein (ccsp) but not c-kit, cd34, and p63, indicating that they represent a subpopulation o ...	2006	16772384
[serological analysis of sars coronavirus in children diagnosed clinically as severe acute respiratory syndrome cases during sars epidemic in beijing].	to identify the etiologic agents from children who had been clinically diagnosed as severe acute respiratory syndrome (sars) during the epidemic in beijing and to characterize the transmissibility of sars from those children to others.	2006	16780645
amino acids 15-28 in the ectodomain of sars coronavirus 3a protein induces neutralizing antibodies.	a synthetic peptide corresponding to amino acids (aa) 15-28 of the severe acute respiratory syndrome coronavirus (sars-cov) 3a protein was used to raise polyclonal antibodies in rabbits. this anti-3a n-terminal antibody could detect 3a protein in infected cells, as did an anti-3a c-terminal antibody previously described. the latter targeted the c-terminal cytoplasmic domain of 3a (aa 134-274). the anti-3a n-terminal antibody could detect intracellular 3a as well as 3a expressed on the cell surfa ...	2006	16781713
long-lived effector/central memory t-cell responses to severe acute respiratory syndrome coronavirus (sars-cov) s antigen in recovered sars patients.	the role of cell-mediated immunity in human sars-cov infection is still not well understood. in this study, we found that memory t-cell responses against the spike (s) protein were persistent for more than 1 year after sars-cov infection by detecting the production of ifn-gamma using elisa and elispot assays. flow cytometric analysis showed that both cd4(+) and cd8(+) t cells were involved in cellular responses against sars-cov infection. interestingly, most of sars-cov s-specific memory cd4(+) ...	2006	16781892
deciphering the biosynthetic codes for the potent anti-sars-cov cyclodepsipeptide valinomycin in streptomyces tsusimaensis atcc 15141.	valinomycin was recently reported to be the most potent agent against severe acute respiratory-syndrome coronavirus (sars-cov) in infected vero e6 cells. aimed at generating analogues by metabolic engineering, the valinomycin biosynthetic gene cluster has been cloned from streptomyces tsusimaensis atcc 15141. targeted disruption of a nonribosomal peptide synthetase (nrps) gene abolishes valinomycin production, which confirms its predicted nonribosomal-peptide origin. sequence analysis of the nrp ...	2006	16511823
respiratory viral threats.	to assess new information from peer-reviewed publications in 2005 regarding emerging respiratory viral threats.	2006	16514342
severe acute respiratory syndrome (sars) coronavirus: application of monoclonal antibodies and development of an effective vaccine.	sars-cov is a new type of human coronavirus identified as a causative agent of severe acute respiratory syndrome (sars). on the occasion of the sars outbreak, various monoclonal antibodies (mabs) against sars-cov have been developed and applied for diagnosis, clinical management and basic research. in this review, we overview the biochemical and functional properties and applications of these sars-cov mabs. we also focus on a variety of vaccines currently under development and discuss the immune ...	2006	16518829
a human neutralizing antibody against a conformational epitope shared by oligomeric sars s1 protein.	an antibody phage-display library was constructed from the b cells of convalescent severe acute respiratory syndrome (sars) patients and screened using inactivated sars coronavirus (cov) virions as antigens. more than 80 positive clones were isolated from the library and one of them, scfv h12, was extensively characterized. scfv h12 bound to sars-cov with high affinity (equilibrium dissociation constant, kd=73.5 nm), and neutralized sars virions in vitro. the facts that scfv h12 bound to the sar ...	2006	16518967
furin cleavage of the sars coronavirus spike glycoprotein enhances cell-cell fusion but does not affect virion entry.	the fusogenic potential of class i viral envelope glycoproteins is activated by proteloytic cleavage of the precursor glycoprotein to generate the mature receptor-binding and transmembrane fusion subunits. although the coronavirus (cov) s glycoproteins share membership in this class of envelope glycoproteins, cleavage to generate the respective s1 and s2 subunits appears absent in a subset of cov species, including that responsible for the severe acute respiratory syndrome (sars). to determine w ...	2006	16519916
severe acute respiratory syndrome coronavirus entry into host cells: opportunities for therapeutic intervention.	a novel human coronavirus (cov) has been identified as the etiological agent that caused the severe acute respiratory syndrome (sars) outbreak in 2003. the spike (s) protein of this virus is a type i surface glycoprotein that mediates binding of the virus to the host receptor and the subsequent fusion between the viral and host membranes. because of its critical role in viral entry, the s protein is an important target for the development of anti-sars cov therapeutics and prophylactics. this art ...	2006	16521129
false-positive results in a recombinant severe acute respiratory syndrome-associated coronavirus (sars-cov) nucleocapsid-based western blot assay were rectified by the use of two subunits (s1 and s2) of spike for detection of antibody to sars-cov.	to evaluate the reactivity of the recombinant proteins expressed in escherichia coli strain bl21(de3), a western blot assay was performed by using a panel of 78 serum samples obtained, respectively, from convalescent-phase patients infected with severe acute respiratory syndrome-associated coronavirus (sars-cov) (30 samples) and from healthy donors (48 samples). as antigen for detection of sars-cov, the nucleocapsid protein (n) showed high sensitivity and strong reactivity with all samples from ...	2006	16522785
severe acute respiratory syndrome diagnostics using a coronavirus protein microarray.	to monitor severe acute respiratory syndrome (sars) infection, a coronavirus protein microarray that harbors proteins from sars coronavirus (sars-cov) and five additional coronaviruses was constructed. these microarrays were used to screen approximately 400 canadian sera from the sars outbreak, including samples from confirmed sars-cov cases, respiratory illness patients, and healthcare professionals. a computer algorithm that uses multiple classifiers to predict samples from sars patients was d ...	2006	16537477
functional characterization of heptad repeat 1 and 2 mutants of the spike protein of severe acute respiratory syndrome coronavirus.	to understand the roles of heptad repeat 1(hr1) and hr2 of the spike (s) protein of the severe acute respiratory syndrome coronavirus (sars-cov) in virus-cell interactions, the conserved leu or ile residues located at positions 913, 927, 941, and 955 in hr1 and 1151, 1165, and 1179 in hr2 were individually replaced with an alpha-helix-breaker pro residue. the 913p mutant was expressed mainly as a faster-migrating, lower-molecular-weight s(l) form, while the wild type and all other mutants produc ...	2006	16537590
evolutionary implications of avian infectious bronchitis virus (aibv) analysis.	for developing efficient vaccines, it is essential to identify which amino acid changes are most important to the survival of the virus. we investigate the amino acid substitution features in the avian infectious bronchitis virus (aibv) antigenic domain of a vaccine serotype (de072) and a virulent viral strain (ga98) to better understand adaptive evolution of aibv. in addition, the sars coronavirus (sars-cov) was also analyzed in the same way. it is interesting to find that extreme comparability ...	2006	16541132
novel five-membered iminocyclitol derivatives as selective and potent glycosidase inhibitors: new structures for antivirals and osteoarthritis.	a novel 5-membered iminocyclitol derivative was found to be a potent and selective inhibitor of the glycoprotein-processing alpha-glucosidase with a ki value of 53 nm. this compound was further derivatized to antiviral agents against japanese encephalitis virus, dengue virus serotype 2 (den-2), human sars coronavirus, and human beta-hexosaminidase (ki = 2.6 nm), a new target for the development of osteoarthritis therapeutics.	2006	16397876
who owns the genome?		2006	16789312
nonhuman primate models for sars.		2006	16608385
nucleic-acid-based antiviral agents against positive single-stranded rna viruses.	positive single-stranded rna viruses constitute a broad and prevalent group of pathogens that threaten human health and life worldwide. while effective vaccines have been developed for some, such as poliovirus and hepatitis a, others such as coxsackievirus, severe acute respiratory syndrome coronavirus (sars-cov) and west nile virus have no accredited drug treatments. antisense technologies, which encompass small interfering rna, antisense oligonucleotides, ribozymes and their chemically modifie ...	2006	16610761
understanding helicases as a means of virus control.	helicases are promising antiviral drug targets because their enzymatic activities are essential for viral genome replication, transcription, and translation. numerous potent inhibitors of helicases encoded by herpes simplex virus, severe acute respiratory syndrome coronavirus, hepatitis c virus, japanese encephalitis virus, west nile virus, and human papillomavirus have been recently reported in the scientific literature. some inhibitors have also been shown to decrease viral replication in cell ...	2006	16611118
characterization and inhibition of sars-coronavirus main protease.	severe acute respiratory syndrome (sars) is an emerging infectious disease caused by a novel human coronavirus (cov). during the 2003 epidemic, the disease rapidly spread from its origin in southern china to other countries and affected almost 8000 patients, which resulted in about 800 fatalities. a chymotrypsin-like cysteine protease named 3c-like protease (3clpro) is essential for the life cycle of the sars-cov. this main protease is responsible for maturation of functional proteins and repres ...	2006	16611148
animal origins of the severe acute respiratory syndrome coronavirus: insight from ace2-s-protein interactions.		2006	16611880
a single amino acid substitution (r441a) in the receptor-binding domain of sars coronavirus spike protein disrupts the antigenic structure and binding activity.	the spike (s) protein of severe acute respiratory syndrome coronavirus (sars-cov) has two major functions: interacting with the receptor to mediate virus entry and inducing protective immunity. coincidently, the receptor-binding domain (rbd, residues 318-510) of sar-cov s protein is a major antigenic site to induce neutralizing antibodies. here, we used rbd-fc, a fusion protein containing the rbd and human igg1 fc, as a model in the studies and found that a single amino acid substitution in the ...	2006	16615996
inhibition of severe acute respiratory syndrome-associated coronavirus (sars-cov) infectivity by peptides analogous to the viral spike protein.	severe acute respiratory syndrome-associated coronavirus (sars-cov) is the cause of an atypical pneumonia that affected asia, north america and europe in 2002-2003. the viral spike (s) glycoprotein is responsible for mediating receptor binding and membrane fusion. recent studies have proposed that the carboxyl terminal portion (s2 subunit) of the s protein is a class i viral fusion protein. the wimley and white interfacial hydrophobicity scale was used to identify regions within the cov s2 subun ...	2006	16616792
[enhanced-real time pcr: a highly sensitive method for sars-coronavirus detection].	an enhanced real-time polymerase chain reaction (ert-pcr) assay to detect the coronavirus associated with severe acute respiratory syndrome (sars-cov) has been designed for detection of sars-cov with high sensitivity and easy-to-interpret results, in which a target gene pre-amplification step preceded taqman real-time fluorescent pcr. the limit of detection of the ert-pcr method was 10(-2) higher than the standard real-time pcr assay and 10(-7) higher than conventional pcr methods. the increased ...	2006	16617369
enhancement of the infectivity of sars-cov in balb/c mice by imp dehydrogenase inhibitors, including ribavirin.	because of the conflicting data concerning the sars-cov inhibitory efficacy of ribavirin, an inosine monophosphate (imp) dehydrogenase inhibitor, studies were done to evaluate the efficacy of ribavirin and other imp dehydrogenase inhibitors (5-ethynyl-1-beta-d-ribofuranosylimidazole-4-carboxamide (eicar), mizoribine, and mycophenolic acid) in preventing viral replication in the lungs of balb/c mice, a replication model for severe acute respiratory syndrome (sars) infections (subbarao, k., mcauli ...	2006	16621037
immunization with sars-cov s dna vaccine generates memory cd4+ and cd8+ t cell immune responses.	an effective vaccine for severe acute respiratory syndrome (sars) will probably require the generation and maintenance of both humoral and cellular immune responses. it has been reported that after natural infection in humans and immunization in animals with sars-cov vaccine, antibody is produced and persistent for a long period of time. in the present study, mice were immunized i.m. with sars-cov s dna vaccine, and three different methods (elisa, elispot and facs) were used to evaluate the immu ...	2006	16621188
[expression and significance of severe acute respiratory syndrome associated coronavirus (sars-cov)-x4 protein in lungs of sars patients].	to investigate the significance of severe acute respiratory syndrome associated coronavirus (sars-cov)-x4 protein expression in lungs of patients with sars.	2006	16624149
[variability analysis of s2 gene of sars-cov].	to determine the sequence of s2 gene of sars-associated coronavirus (sars-cov) gd322 and analyze the phyletic evolution of s2 gene.	2006	16624753
polymorphism of sars-cov genomes.	in this work, severe acute respiratory syndrome associated coronavirus (sars-cov) genome bj202 (ay864806) was completely sequenced. the genome was directly accessed from the stool sample of a patient in beijing. comparative genomics methods were used to analyze the sequence variations of 116 sars-cov genomes (including bj202) available in the ncbi genbank. with the genome sequence of gz02 as the reference, there were 41 polymorphic sites identified in bj202 and a total of 278 polymorphic sites p ...	2006	16625834
crystal structure of the severe acute respiratory syndrome (sars) coronavirus nucleocapsid protein dimerization domain reveals evolutionary linkage between corona- and arteriviridae.	the causative agent of severe acute respiratory syndrome (sars) is the sars-associated coronavirus, sars-cov. the nucleocapsid (n) protein plays an essential role in sars-cov genome packaging and virion assembly. we have previously shown that sars-cov n protein forms a dimer in solution through its c-terminal domain. in this study, the crystal structure of the dimerization domain, consisting of residues 270-370, is determined to 1.75a resolution. the structure shows a dimer with extensive intera ...	2006	16627473
hla-a*0201 t-cell epitopes in severe acute respiratory syndrome (sars) coronavirus nucleocapsid and spike proteins.	the immunogenicity of hla-a*0201-restricted cytotoxic t lymphocyte (ctl) peptide in severe acute respiratory syndrome coronavirus (sars-cov) nuclear capsid (n) and spike (s) proteins was determined by testing the proteins' ability to elicit a specific cellular immune response after immunization of hla-a2.1 transgenic mice and in vitro vaccination of hla-a2.1 positive human peripheral blood mononuclearcytes (pbmcs). first, we screened sars n and s amino acid sequences for allele-specific motif ma ...	2006	16630549
mapping a neutralizing epitope on the sars coronavirus spike protein: computational prediction based on affinity-selected peptides.	rapid elucidation of neutralizing antibody epitopes on emerging viral pathogens like severe acute respiratory syndrome (sars) coronavirus (cov) or highly pathogenic avian influenza h5n1 virus is of great importance for rational design of vaccines against these viruses. here we combined screening of phage display random peptide libraries with a unique computer algorithm "mapitope" to identify the discontinuous epitope of 80r, a potent neutralizing human anti-sars monoclonal antibody against the s ...	2006	16630634
sometimes intermediates. do the job!	the sars coronavirus main proteinase is a prime target for antiviral therapy. in this issue of chemistry & biology, wu et al. describe potent inhibition of the enzyme by benzotriazole esters, which were originally obtained as intermediates in the synthesis of lopinavir derivatives .	2006	16638527
stable benzotriazole esters as mechanism-based inactivators of the severe acute respiratory syndrome 3cl protease.	severe acute respiratory syndrome (sars) is caused by a newly emerged coronavirus that infected more than 8000 individuals and resulted in more than 800 fatalities in 2003. currently, there is no effective treatment for this epidemic. sars-3cl(pro) has been shown to be essential for replication and is thus a target for drug discovery. here, a class of stable benzotriazole esters was reported as mechanism-based inactivators of 3cl(pro), and the most potent inactivator exhibited a k(inact) of 0.00 ...	2006	16638531
kinetics and synergistic effects of sirnas targeting structural and replicase genes of sars-associated coronavirus.	sars-associated coronavirus was identified as the etiological agent of severe acute respiratory syndrome and a large virus pool was identified in wild animals. virus generates drug resistance through fast mutagenesis and escapes antiviral treatment. sirnas targeting different genes would be an alternative for overcoming drug resistance. here, we report effective sirnas targeting structural genes (i.e., spike, envelope, membrane, and nucleocapsid) and their antiviral kinetics. we also showed the ...	2006	16638566
design and synthesis of hydroxyferroquine derivatives with antimalarial and antiviral activities.	three ferroquine (fq) derivatives, closely mimicking the antimalarial drug hydroxychloroquine (hcq), have been prepared. whereas these organometallic compounds provide the expected reduced cytotoxic effects compared to fq, they inhibit in vitro growth of plasmodium falciparum far better than chloroquine (cq). moreover, this new class of bioorganometallic compounds exert antiviral effects with some selectivity toward sars-cov infection. these new drugs may offer an interesting alternative for asi ...	2006	16640347
enzymatic activity of the sars coronavirus main proteinase dimer.	the enzymatic activity of the sars coronavirus main proteinase dimer was characterized by a sensitive, quantitative assay. the new, fluorogenic substrate, (ala-arg-leu-gln-nh)(2)-rhodamine, contained a severe acute respiratory syndrome coronavirus (sars cov) main proteinase consensus cleavage sequence and rhodamine 110, one of the most detectable compounds known, as the reporter group. the gene for the enzyme was cloned in the absence of purification tags, expressed in escherichia coli and the e ...	2006	16647061
nasopharyngeal shedding of severe acute respiratory syndrome-associated coronavirus is associated with genetic polymorphisms.	a high initial or peak severe acute respiratory syndrome (sars)-associated coronavirus (sars-cov) load in nasopharyngeal specimens was shown to be associated with a high mortality rate. because all infected individuals were devoid of preeexisting protective immunity against sars-cov, the biological basis for the variable virus burdens in different patients remains elusive.	2006	16652313
cross-neutralization of human and palm civet severe acute respiratory syndrome coronaviruses by antibodies targeting the receptor-binding domain of spike protein.	the spike (s) protein of severe acute respiratory syndrome coronavirus (sars-cov) is considered as a protective ag for vaccine design. we previously demonstrated that the receptor-binding domain (rbd) of s protein contains multiple conformational epitopes (conf i-vi) that confer the major target of neutralizing abs. here we show that the recombinant rbds derived from the s protein sequences of tor2, gd03, and sz3, the representative strains of human 2002-2003 and 2003-2004 sars-cov and palm cive ...	2006	16670317
epidemiologic study and containment of a nosocomial outbreak of severe acute respiratory syndrome in a medical center in kaohsiung, taiwan.	we conducted an epidemiologic investigation at the beginning of a nosocomial outbreak of severe acute respiratory syndrome (sars) to clarify the dynamics of sars transmission, the magnitude of the sars outbreak, and the impact of the outbreak on the community.	2006	16671027
cluster of cases of severe acute respiratory syndrome among toronto healthcare workers after implementation of infection control precautions: a case series.	to review the severe acute respiratory syndrome (sars) infection control practices, the types of exposure to patients with sars, and the activities associated with treatment of such patients among healthcare workers (hcws) who developed sars in toronto, canada, after sars-specific infection control precautions had been implemented.	2006	16671028
hospital waste generation during an outbreak of severe acute respiratory syndrome in taiwan.	during the sars outbreak in taiwan, the number of ambulatory patients and inpatients treated at one medical center decreased by 40%-70% because of the increasing number of sars patients. at the peak of the epidemic, the amount of hospital infectious waste had increased from a norm of 0.85 kg per patient-day to 2.7 kg per patient-day. however, the hospital was able to return the generation of waste to normal levels within 10 days.	2006	16671038
airborne severe acute respiratory syndrome coronavirus concentrations in a negative-pressure isolation room.	this study used a sensitive polymerase chain reaction method coupled with filter sampling to detect the presence of airborne severe acute respiratory syndrome (sars) coronavirus in an isolation patient room with a patient with severe acute respiratory syndrome receiving mechanical ventilatory support. polymerase chain reaction results were negative for sars coronavirus in room air both before and after patient extubation.	2006	16671039
inhibition of feline (fipv) and human (sars) coronavirus by semisynthetic derivatives of glycopeptide antibiotics.	various semisynthetic derivatives of glycopeptide antibiotics including vancomycin, eremomycin, teicoplanin, ristocetin a and da-40926 have been evaluated for their inhibitory activity against feline infectious peritonitis virus (fipv) and human (sars-cov, frankfurt-1 strain) coronavirus in cell culture in comparison with their activity against human immunodeficiency virus (hiv). several glycopeptide derivatives modified with hydrophobic substituents showed selective antiviral activity. for the ...	2006	16675038
a simple method for preparing synthetic controls for conventional and real-time pcr for the identification of endemic and exotic disease agents.	medical and veterinary diagnostic and public health laboratories world-wide are increasingly being called upon to introduce molecular diagnostic tests for both endemic and exotic diseases. this demand has accelerated following increasing terrorism fears. ironically these same concerns have lead to tightening of both import and export controls preventing many laboratories, particularly those outside of the united states, from gaining access to positive control material. this in turn has prevented ...	2006	16677717
induction of protective immunity against severe acute respiratory syndrome coronavirus (sars-cov) infection using highly attenuated recombinant vaccinia virus dis.	sars-coronavirus (sars-cov) has recently been identified as the causative agent of sars. we constructed a series of recombinant dis (rdis), a highly attenuated vaccinia strain, expressing a gene encoding four structural proteins (e, m, n and s) of sars-cov individually or simultaneously. these rdis elicited sars-cov-specific serum igg antibody and t-cell responses in vaccinated mice following intranasal or subcutaneous administration. mice that were subcutaneously vaccinated with rdis expressing ...	2006	16678878
production of an anti-severe acute respiratory syndrome (sars) coronavirus human monoclonal antibody fab fragment by using a combinatorial immunoglobulin gene library derived from patients who recovered from sars.	a combinatorial human immunoglobulin gene library was constructed from the peripheral lymphocytes of two patients who recovered from severe acute respiratory syndrome (sars). the library was screened for the production of fab antibody fragments to a recombinant spike protein of sars-associated coronavirus (sars-cov). one fab clone, as3-3, reacted with the spike protein in an enzyme-linked immunosorbent assay. the dissociation constant of as3-3 was 1.98 x 10(-8) m. immunofluorescent microscopy re ...	2006	16682481
risk-stratified seroprevalence of severe acute respiratory syndrome coronavirus among children in hong kong.	severe acute respiratory syndrome was relatively mild in children, and the incidence was significantly lower when compared with adults. although previous seroepidemiological studies demonstrated that asymptomatic infection was uncommon among health care workers and adult contacts of patients with severe acute respiratory syndrome, it is unclear whether this would extend to the pediatric population.	2006	16682490
mitochondrial location of severe acute respiratory syndrome coronavirus 3b protein.	severe acute respiratory syndrome-associated coronavirus (sars-cov), a distant member of the group 2 coronaviruses, has recently been identified as the etiological agent of severe acute respiratory syndrome (sars). the genome of sars-cov contains four structural genes that are homologous to genes found in other coronaviruses, as well as six subgroup-specific open reading frames (orfs). orf3 encodes a predicted 154-amino-acid protein that lacks similarity to any known protein, and is designated 3 ...	2006	16682811
biochemical evidence for the presence of mixed membrane topologies of the severe acute respiratory syndrome coronavirus envelope protein expressed in mammalian cells.	coronavirus envelope (e) protein is a small integral membrane protein with multi-functions in virion assembly, morphogenesis and virus-host interaction. different coronavirus e proteins share striking similarities in biochemical properties and biological functions, but seem to adopt distinct membrane topology. in this report, we study the membrane topology of the sars-cov e protein by immunofluorescent staining of cells differentially permeabilized with detergents and proteinase k protection ass ...	2006	16684538
an efficient method for the synthesis of peptide aldehyde libraries employed in the discovery of reversible sars coronavirus main protease (sars-cov mpro) inhibitors.	a method for the parallel solid-phase synthesis of peptide aldehydes has been developed. protected amino acid aldehydes obtained by the racemization-free oxidation of amino alcohols with dess-martin periodinane were immobilized on threonyl resins as oxazolidines. following boc protection of the ring nitrogen to yield the n-protected oxazolidine linker, peptide synthesis was performed efficiently on this resin. a peptide aldehyde library was designed for targeting the sars coronavirus main protea ...	2006	16688706
sars-cov virus-host interactions and comparative etiologies of acute respiratory distress syndrome as determined by transcriptional and cytokine profiling of formalin-fixed paraffin-embedded tissues.	these studies attempt to understand more fully the host response and pathogenesis associated with severe acute respiratory syndrome (sars) coronavirus (sars-cov) by monitoring gene expression using formalin-fixed paraffin-embedded (ffpe) pulmonary autopsy tissues. these tissues were from patients in different hospitals in singapore who were diagnosed with various microbial infections, including sars-cov, that caused acute respiratory distress syndrome (ards). global expression patterns showed li ...	2006	16689659
long-lived memory t lymphocyte responses against sars coronavirus nucleocapsid protein in sars-recovered patients.	the nucleocapsid (n) protein is a structural component of severe acute respiratory syndrome (sars) coronavirus (sars-cov) and can induce antibody responses in sars patients during infection. however, it is not known whether sars-cov n protein can induce a long persistence of memory t-cell response in human. in this study, we found that peripheral blood mononuclear cells (pbmcs) from fully recovered sars individuals rapidly produced ifn-gamma and il-2 following stimulation with a pool of overlapp ...	2006	16690096
analysis of ace2 in polarized epithelial cells: surface expression and function as receptor for severe acute respiratory syndrome-associated coronavirus.	the primary target of severe acute respiratory syndrome-associated coronavirus (sars-cov) is epithelial cells in the respiratory and intestinal tract. the cellular receptor for sars-cov, angiotensin-converting enzyme 2 (ace2), has been shown to be localized on the apical plasma membrane of polarized respiratory epithelial cells and to mediate infection from the apical side of these cells. here, these results were confirmed and extended by including a colon carcinoma cell line (caco-2), a lung ca ...	2006	16690935
environmental transmission of sars at amoy gardens.	recent investigations into the march 2003 outbreak of sars in hong kong have concluded that environmental factors played an important role in the transmission of the disease. these studies have focused on a particular outbreak event, the rapid spread of sars throughout amoy gardens, a large, private apartment complex. they have demonstrated that, unlike a typical viral outbreak that is spread through person-to-person contact, the sars virus in this case was spread primarily through the air. high ...	2006	16696450
template-based coiled-coil antigens elicit neutralizing antibodies to the sars-coronavirus.	the spike (s) glycoprotein of coronaviruses (cov) mediates viral entry into host cells. it contains two hydrophobic heptad repeat (hr) regions, denoted hrn and hrc, which oligomerize the s glycoprotein into a trimer in the native state and when activated collapse into a six-helix bundle structure driving fusion of the host and viral membranes. previous studies have shown that peptides of the hr regions can inhibit viral infectivity. these studies imply that the hr regions are accessible and that ...	2006	16697221
template-based coiled-coil antigens elicit neutralizing antibodies to the sars-coronavirus.	the spike (s) glycoprotein of coronaviruses (cov) mediates viral entry into host cells. it contains two hydrophobic heptad repeat (hr) regions, denoted hrn and hrc, which oligomerize the s glycoprotein into a trimer in the native state and when activated collapse into a six-helix bundle structure driving fusion of the host and viral membranes. previous studies have shown that peptides of the hr regions can inhibit viral infectivity. these studies imply that the hr regions are accessible and that ...	2006	16697221
structures and polymorphic interactions of two heptad-repeat regions of the sars virus s2 protein.	entry of sars coronavirus into its target cell requires large-scale structural transitions in the viral spike (s) glycoprotein in order to induce fusion of the virus and cell membranes. here we describe the identification and crystal structures of four distinct alpha-helical domains derived from the highly conserved heptad-repeat (hr) regions of the s2 fusion subunit. the four domains are an antiparallel four-stranded coiled coil, a parallel trimeric coiled coil, a four-helix bundle, and a six-h ...	2006	16698550
[emergent viruses: sars-associate coronavirus and h5n1 influenza virus].	two viral agents with rna genome are responsible for emerging illnesses: influenza virus a/h5n1 and severe acute respiratory syndrome virus (sars). for the diagnosis of sars virus infection, an epidemiological investigation is necessary to know whether the patient has been exposed to a risk in a country where the sars virus is circulating or whether the patient had worked in a laboratory handling sars virus. the detection of sars virus is possible in various clinical samples (including urine) by ...	2006	16698555
model of a putative pore: the pentameric alpha-helical bundle of sars coronavirus e protein in lipid bilayers.	the coronavirus responsible for the severe acute respiratory syndrome contains a small envelope protein, e, with putative involvement in host apoptosis and virus morphogenesis. to perform these functions, it has been suggested that protein e can form a membrane destabilizing transmembrane (tm) hairpin, or homooligomerize to form a tm pore. indeed, in a recent study we reported that the alpha-helical putative transmembrane domain of e protein (etm) forms several sds-resistant tm interactions: a d ...	2006	16698774
[the research and development of new diagnostic gene chips for sars coronavirus].	the loci of cdna sequences for valid diagnosis have been identified through the selection of the genome of sars coronaries. the gene chips for diagnosing such virus have been developed, based on our own-developed technology for manufacturing and application of gene chips. the diagnoses given by such gene chips were consistent well with the reports of clinical laboratories (94.29%) and the sensitivity reached 10(-2)/ml virus molecules. this method is well suited for the clinical use in sars coron ...	2006	16706344
thin-section ct 12 months after the diagnosis of severe acute respiratory syndrome in pediatric patients.	the objective of our study was to report the thin-section ct findings 12 months after the diagnosis of severe acute respiratory syndrome (sars) in pediatric patients who had recovered clinically but had persistent abnormal ct findings 6 months after the diagnosis. the clinical data for these patients were correlated to identify risk factors that might increase the likelihood of the development of ct abnormalities.	2006	16714663
anti-sars drug screening by molecular docking.	starting from a collection of 1386 druggable compounds obtained from the 3d pharmacophore search, we performed a similarity search to narrow down the scope of docking studies. the template molecule is kz7088 (chou et al., 2003, biochem biophys res commun 308: 148-151). the mdl maccs keys were used to fingerprint the molecules. the tanimoto coefficient is taken as the metric to compare fingerprints. if the similarity threshold was 0.8, a set of 50 unique hits and 103 conformers were retrieved as ...	2006	16715412
efficacy of severe acute respiratory syndrome vaccine based on a nonhuman primate adenovirus in the presence of immunity against human adenovirus.	replication-deficient human adenovirus type 5 (adh5) vectors can induce strong transgene product-specific cellular and humoral responses. however, many adult humans have neutralizing antibodies (nabs) against adh5 as a result of natural infection with this virus. therefore, a chimpanzee adenovirus c7 (adc7) vector was developed to circumvent interference by preexisting immunity to adh5. this study evaluated the impact of preexisting immunity to human adenovirus on the efficacy of adenovirus-base ...	2006	16716107
investigation of interaction between two neutralizing monoclonal antibodies and sars virus using biosensor based on imaging ellipsometry.	two neutralizing human scfv, b1 and h12 were identified initially using elisa,employing highly purified virus as the coating antigen. the biosensor technique based on imaging ellipsometry was employed directly to detect two neutralizing monoclonal antibodies and serial serum samples from 10 sars patients and 12 volunteers who had not sars. further, the kinetic process of interaction between the antibodies and sars-cov was studied using the real-time function of the biosensor. the biosensor is co ...	2006	16718402
serum amyloid a is not useful in the diagnosis of severe acute respiratory syndrome.		2006	16723685
identification and characterization of novel neutralizing epitopes in the receptor-binding domain of sars-cov spike protein: revealing the critical antigenic determinants in inactivated sars-cov vaccine.	the spike (s) protein of severe acute respiratory syndrome coronavirus (sars-cov) is considered as a major antigen for vaccine design. we previously demonstrated that the receptor-binding domain (rbd: residues 318-510) of s protein contains multiple conformation-dependent neutralizing epitopes (conf i to vi) and serves as a major target of sars-cov neutralization. here, we further characterized the antigenic structure in the rbd by a panel of novel mabs isolated from the mice immunized with an i ...	2006	16725238
significant redox insensitivity of the functions of the sars-cov spike glycoprotein: comparison with hiv envelope.	the capacity of the surface glycoproteins of enveloped viruses to mediate virus/cell binding and membrane fusion requires a proper thiol/disulfide balance. chemical manipulation of their redox state using reducing agents or free sulfhydryl reagents affects virus/cell interaction. conversely, natural thiol/disulfide rearrangements often occur during the cell interaction to trigger fusogenicity, hence the virus entry. we examined the relationship between the redox state of the 20 cysteine residues ...	2006	16418166
longitudinal profile of antibodies against sars-coronavirus in sars patients and their clinical significance.	severe acute respiratory syndrome (sars) is a newly discovered disease caused by a novel coronavirus. the present study studied the longitudinal profile of antibodies against sars-coronavirus (sars-cov) in sars patients and evaluated the clinical significance of these antibodies.	2006	16423201
the expression of membrane protein augments the specific responses induced by sars-cov nucleocapsid dna immunization.	nucleocapsid protein plays a critical role in sars-cov pathogenesis, and high-level anti-nucleocapsid antibodies are detected in the patients infected by severe acute respiratory syndrome-associated coronavirus (sars-cov). several studies have shown that there exists an interaction between nucleocapsid (n) and membrane (m) protein. in this paper, we investigate whether the expression of membrane protein can affect the immune responses induced by nucleocapsid dna immunization. two recombinant pla ...	2006	16423399