| solution structure of the severe acute respiratory syndrome-coronavirus heptad repeat 2 domain in the prefusion state. | the envelope glycoprotein, termed the spike protein, of severe acute respiratory syndrome coronavirus (sars-cov) is known to mediate viral entry. similar to other class 1 viral fusion proteins, the heptad repeat regions of sars-cov spike are thought to undergo conformational changes from a prefusion form to a subsequent post-fusion form that enables fusion of the viral and host membranes. recently, the structure of a post-fusion form of sars-cov spike, which consists of isolated domains of hepta ... | 2006 | 16507566 |
| identification of critical determinants on ace2 for sars-cov entry and development of a potent entry inhibitor. | severe acute respiratory syndrome (sars) is caused by a novel coronavirus, sars-cov. virus entry into cells is mediated through interactions between spike (s) glycoprotein and angiotensin-converting enzyme 2 (ace2). alanine scanning mutagenesis analysis was performed to identify determinants on ace2 critical for sars-cov infection. results indicated that charged amino acids between residues 22 and 57 were important, k26 and d30, in particular. peptides representing various regions of ace2 critic ... | 2006 | 16510163 |
| structure of the sars coronavirus main proteinase as an active c2 crystallographic dimer. | the 34 kda main proteinase (mpro) from the severe acute respiratory syndrome coronavirus (sars-cov) plays an important role in the virus life cycle through the specific processing of viral polyproteins. as such, sars-cov mpro is a key target for the identification of specific inhibitors directed against the sars virus. with a view to facilitating the development of such compounds, crystals were obtained of the enzyme at ph 6.5 in the orthorhombic space group p2(1)2(1)2 that diffract to a resolut ... | 2005 | 16511208 |
| 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 |
| developments in antiviral drug design, discovery and development in 2004. | this article summarizes key aspects of progress made during 2004 toward the design, discovery and development of antiviral agents for clinical use. important developments in the identification, characterization and clinical utility of inhibitors of human immunodeficiency virus; the hepatitis viruses, hepatitis b, hepatitis c; the herpes family of viruses, herpes simplex viruses 1 and 2, varicella zoster virus, epstein-barr virus and human cytomegalovirus; the respiratory viruses, influenza, resp ... | 2005 | 16535860 |
| [lung pathology and pathogenesis of severe acute respiratory syndrome: a report of six full autopsies]. | severe acute respiratory syndrome (sars) is an emerging infectious disease that first manifested in humans in november 2002. the sars-associated coronavirus (sars-cov) has been identified as the causal agent, but the pathology and pathogenesis are still not quite clear. | 2005 | 16536279 |
| coronaviruses in poultry and other birds. | the number of avian species in which coronaviruses have been detected has doubled in the past couple of years. while the coronaviruses in these species have all been in coronavirus group 3, as for the better known coronaviruses of the domestic fowl (infectious bronchitis virus [ibv], in gallus gallus), turkey (meleagris gallopavo) and pheasant (phasianus colchicus), there is experimental evidence to suggest that birds are not limited to infection with group 3 coronaviruses. in china coronaviruse ... | 2005 | 16537157 |
| coronaviruses in poultry and other birds. | the number of avian species in which coronaviruses have been detected has doubled in the past couple of years. while the coronaviruses in these species have all been in coronavirus group 3, as for the better known coronaviruses of the domestic fowl (infectious bronchitis virus [ibv], in gallus gallus), turkey (meleagris gallopavo) and pheasant (phasianus colchicus), there is experimental evidence to suggest that birds are not limited to infection with group 3 coronaviruses. in china coronaviruse ... | 2005 | 16537157 |
| 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 |
| sars patients-derived human recombinant antibodies to s and m proteins efficiently neutralize sars-coronavirus infectivity. | to develop a specific sars virus-targeted antibody preparation for emergent prophylaxis and treatment of sars virus infection. | 2005 | 16544518 |
| nucleocapsid protein of sars-cov activates the expression of cyclooxygenase-2 by binding directly to regulatory elements for nuclear factor-kappa b and ccaat/enhancer binding protein. | sars-associated coronavirus (sars-cov) causes inflammation and damage to the lungs resulting in severe acute respiratory syndrome. to evaluate the molecular mechanisms behind this event, we investigated the roles of sars-cov proteins in regulation of the proinflammatory factor, cyclooxygenase-2 (cox-2). individual viral proteins were tested for their abilities to regulate cox-2 gene expression. results showed that the cox-2 promoter was activated by the nucleocapsid (n) protein in a concentratio ... | 2006 | 16546436 |
| [antigenicity analysis of nucleocapsid proteins of 3 human coronaviruses sars-cov, 229e and oc43 with their monoclonal antibodies]. | to prepare and characterize monoclonal antibodies (mabs) against the recombinant nucleocapsid (n) protein of 3 human coronaviruses sars-cov, 229e and oc43 and study the antigenic relationship between the 3 n proteins. | 2006 | 16546729 |
| discovery of an rna virus 3'->5' exoribonuclease that is critically involved in coronavirus rna synthesis. | replication of the giant rna genome of severe acute respiratory syndrome (sars) coronavirus (cov) and synthesis of as many as eight subgenomic (sg) mrnas are mediated by a viral replicase-transcriptase of outstanding complexity that includes an essential endoribonuclease activity. here, we show that the cov replicative machinery, unlike that of other rna viruses, also uses an exoribonuclease (exon) activity, which is associated with nonstructural protein (nsp) 14. bacterially expressed forms of ... | 2006 | 16549795 |
| sars: are we still at risk? | | 2006 | 16550673 |
| high expression level of soluble sars spike protein mediated by adenovirus in hek293 cells. | to develop a highly efficacious method for preparation of soluble sars s-protein using adenovirus vector to meet the requirement for s-protein investigation. | 2006 | 16552820 |
| severe acute respiratory syndrome coronavirus 3c-like protease-induced apoptosis. | the pathogenesis of severe acute respiratory syndrome-associated coronavirus (sars-cov) is an important issue for the treatment and prevention of severe acute respiratory syndrome. recently, sars-cov has been demonstrated to induce cell apoptosis in vero-e6 cells. the possible role of sars-cov 3c-like protease (3clpro) in virus-induced apoptosis is characterized in this study. growth arrest and apoptosis via caspase-3 and caspase-9 activities were demonstrated in sars-cov 3clpro -expressing huma ... | 2006 | 16553810 |
| close relationship between sars-coronavirus and group 2 coronavirus. | the sudden appearance and potential lethality of severe acute respiratory syndrome (sars)-associated coronavirus (sars-cov) in humans has resulted in a focusing of new attention on the determination of both its origins and evolution. the relationship existing between sars-cov and other groups of coronaviruses was determined via analyses of phylogenetic trees and comparative genomic analyses of the coronavirus genes: polymerase (orf1ab), spike (s), envelope (e), membrane (m) and nucleocapsid (n). ... | 2006 | 16554722 |
| only one protomer is active in the dimer of sars 3c-like proteinase. | the severe acute respiratory syndrome coronavirus 3c-like protease has been proposed to be a key target for structurally based drug design against sars. the enzyme exists as a mixture of dimer and monomer, and only the dimer was considered to be active. in this report, we have investigated, using molecular dynamics simulation and mutational studies, the problems as to why only the dimer is active and whether both of the two protomers in the dimer are active. the molecular dynamics simulations sh ... | 2006 | 16565086 |
| inhibition of cytokine gene expression and induction of chemokine genes in non-lymphatic cells infected with sars coronavirus. | sars coronavirus (sars-cov) is the etiologic agent of the severe acute respiratory syndrome. sars-cov mainly infects tissues of non-lymphatic origin, and the cytokine profile of those cells can determine the course of disease. here, we investigated the cytokine response of two human non-lymphatic cell lines, caco-2 and hek 293, which are fully permissive for sars-cov. | 2006 | 16571117 |
| mucosal immunization with surface-displayed severe acute respiratory syndrome coronavirus spike protein on lactobacillus casei induces neutralizing antibodies in mice. | induction of mucosal immunity may be important for preventing sars-cov infections. for safe and effective delivery of viral antigens to the mucosal immune system, we have developed a novel surface antigen display system for lactic acid bacteria using the poly-gamma-glutamic acid synthetase a protein (pgsa) of bacillus subtilis as an anchoring matrix. recombinant fusion proteins comprised of pgsa and the spike (s) protein segments sa (residues 2 to 114) and sb (residues 264 to 596) were stably ex ... | 2006 | 16571824 |
| tertiary structure prediction of sars coronavirus helicase. | sars coronavirus, scv, has been recently responsible of a sudden and widespread infection which caused almost 800 victims. the limited amount of scv protein structural information is partially responsible of the lack of specific drugs against the virus. coronavirus helicases are very conserved and peculiar proteins which have been proposed as suitable targets for antiviral drugs, such as bananins, which have been recently shown to inhibit the scv helicase in vitro. here, the quaternary structure ... | 2006 | 16579970 |
| severe acute respiratory syndrome coronavirus protein 7a interacts with hsgt. | severe acute respiratory syndrome coronavirus (sars-cov) 7a is an accessory protein with no known homologues. in this study, we report the interaction of a sars-cov 7a and small glutamine-rich tetratricopeptide repeat-containing protein (sgt). sars-cov 7a and human sgt interaction was identified using a two-hybrid system screen and confirmed with interaction screens in cell culture and cellular co-localization studies. the sgt domain of interaction was mapped by deletion mutant analysis and resu ... | 2006 | 16580632 |
| angiotensin-converting enzyme 2 in lung diseases. | the renin-angiotensin system (ras) plays a key role in maintaining blood pressure homeostasis, as well as fluid and salt balance. angiotensin ii, a key effector peptide of the system, causes vasoconstriction and exerts multiple biological functions. angiotensin-converting enzyme (ace) plays a central role in generating angiotensin ii from angiotensin i, and capillary blood vessels in the lung are one of the major sites of ace expression and angiotensin ii production in the human body. the ras ha ... | 2006 | 16581295 |
| severe acute respiratory syndrome coronavirus papain-like protease: structure of a viral deubiquitinating enzyme. | replication of severe acute respiratory syndrome (sars) coronavirus (sars-cov) requires proteolytic processing of the replicase polyprotein by two viral cysteine proteases, a chymotrypsin-like protease (3clpro) and a papain-like protease (plpro). these proteases are important targets for development of antiviral drugs that would inhibit viral replication and reduce mortality associated with outbreaks of sars-cov. in this work, we describe the 1.85-a crystal structure of the catalytic core of sar ... | 2006 | 16581910 |
| expression, purification and crystallization of the sars-cov macro domain. | macro domains or x domains are found as modules of multidomain proteins, but can also constitute a protein on their own. recently, biochemical and structural studies of cellular macro domains have been performed, showing that they are active as adp-ribose-1''-phosphatases. macro domains are also present in a number of positive-stranded rna viruses, but their precise function in viral replication is still unknown. the major human pathogen severe acute respiratory syndrome coronavirus (sars-cov) e ... | 2006 | 16582497 |
| crystallization and preliminary x-ray diffraction analysis of nsp15 from sars coronavirus. | the non-structural protein nsp15 from the aetiological agent of sars (severe acute respiratory syndrome) has recently been characterized as a uridine-specific endoribonuclease. this enzyme plays an essential role in viral replication and transcription since a mutation in the related h229e human coronavirus nsp15 gene can abolish viral rna synthesis. sars full-length nsp15 (346 amino acids) has been cloned and expressed in escherichia coli with an n-terminal hexahistidine tag and has been purifie ... | 2006 | 16582498 |
| early diagnosis of sars: lessons from the toronto sars outbreak. | the clinical presentation of sars is nonspecific and diagnostic tests do not provide accurate results early in the disease course. initial diagnosis remains reliant on clinical assessment. to identify features of the clinical assessment that are useful in sars diagnosis, the exposure status and the prevalence and timing of symptoms, signs, laboratory and radiographic findings were determined for all adult patients admitted with suspected sars during the toronto sars outbreak. findings were compa ... | 2006 | 16586072 |
| anti-severe acute respiratory syndrome coronavirus immune responses: the role played by v gamma 9v delta 2 t cells. | severe acute respiratory syndrome (sars) is caused by a novel coronavirus (sars-cov) strain. analyses of t cell repertoires in health care workers who survived sars-cov infection during the 2003 outbreak revealed that their effector memory v gamma 9v delta 2 t cell populations were selectively expanded ~3 months after the onset of disease. no such expansion of their alpha beta t cell pools was detected. the expansion of the v gamma 9v delta 2 t cell population was associated with higher anti-sar ... | 2006 | 16586361 |
| oligonucleotide-based antiviral strategies. | in the age of extensive global traffic systems, the close neighborhood of man and livestock in some regions of the world, as well as inadequate prevention measures and medical care in poorer countries, greatly facilitates the emergence and dissemination of new virus strains. the appearance of avian influenza viruses that can infect humans, the spread of the severe acute respiratory syndrome (sars) virus, and the unprecedented raging of human immunodeficiency virus (hiv) illustrate the threat of ... | 2006 | 16594620 |
| potential antivirals and antiviral strategies against sars coronavirus infections. | there are a number of antivirals as well as antiviral strategies that could be envisaged to prevent or treat severe acute respiratory syndrome (sars) (or similar) coronavirus (cov) infections. targets for the prophylactic or therapeutic interventions include interaction of the spike (s) glycoprotein (s1 domain) with the host cell receptor, fusion of the s2 domain with the host cell membrane, processing of the replicase polyproteins by the virus-encoded proteases (3c-like cysteine protease [3clpr ... | 2006 | 16597209 |
| structure of severe acute respiratory syndrome coronavirus receptor-binding domain complexed with neutralizing antibody. | the severe acute respiratory syndrome coronavirus (sars-cov, or scv), which caused a world-wide epidemic in 2002 and 2003, binds to a receptor, angiotensin-converting enzyme 2 (ace2), through the receptor-binding domain (rbd) of its envelope (spike, s) glycoprotein. the rbd is very immunogenic; it is a major scv neutralization determinant and can elicit potent neutralizing antibodies capable of out-competing ace2. however, the structural basis of rbd immunogenicity, rbd-mediated neutralization, ... | 2006 | 16597622 |
| rapid peptide-based screening on the substrate specificity of severe acute respiratory syndrome (sars) coronavirus 3c-like protease by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. | severe acute respiratory syndrome coronavirus (sars-cov) 3c-like protease (3cl(pro)) mediates extensive proteolytic processing of replicase polyproteins, and is considered a promising target for anti-sars drug development. here we present a rapid and high-throughput screening method to study the substrate specificity of sars-cov 3cl(pro). six target amino acid positions flanking the sars-cov 3cl(pro) cleavage site were investigated. each batch of mixed peptide substrates with defined amino acid ... | 2006 | 16600962 |
| cynomolgus macaque as an animal model for severe acute respiratory syndrome. | the emergence of severe acute respiratory syndrome (sars) in 2002 and 2003 affected global health and caused major economic disruption. adequate animal models are required to study the underlying pathogenesis of sars-associated coronavirus (sars-cov) infection and to develop effective vaccines and therapeutics. we report the first findings of measurable clinical disease in nonhuman primates (nhps) infected with sars-cov. | 2006 | 16605302 |
| acute renal failure in patients with severe acute respiratory syndrome. | severe acute respiratory syndrome (sars) is caused by a new coronavirus, and results in respiratory failure. acute renal failure (arf) may also occur and/or complicate the disease course, however, its incidence, causes and impact in sars patients are not known. | 2005 | 16607445 |
| 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 |
| emodin blocks the sars coronavirus spike protein and angiotensin-converting enzyme 2 interaction. | severe acute respiratory syndrome (sars) is an emerging infectious disease caused by a novel coronavirus (sars-cov). sars-cov spike (s) protein, a type i membrane-bound protein, is essential for the viral attachment to the host cell receptor angiotensin-converting enzyme 2 (ace2). by screening 312 controlled chinese medicinal herbs supervised by committee on chinese medicine and pharmacy at taiwan, we identified that three widely used chinese medicinal herbs of the family polygonaceae inhibited ... | 2007 | 16730806 |
| 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 |