| insight into the activity of sars main protease: molecular dynamics study of dimeric and monomeric form of enzyme. | the phenomenon that sars coronavirus main protease (sars m(pro)) dimer is the main functional form has been confirmed by experiment. however, because of the absence of structural information of the monomer, the reasons for this remain unknown. to investigate it, two molecular dynamics (md) simulations in water for dimer and monomer models have been carried out, using the crystal structure of protomer a of the dimer as the starting structure for the monomer. during the md simulation of dimer, thr ... | 2007 | 17083088 |
| receptor-binding domain of sars-cov spike protein induces long-term protective immunity in an animal model. | development of effective vaccines against severe acute respiratory syndrome (sars) coronavirus (sars-cov) is still a priority in prevention of re-emergence of sars. our previous studies have shown that the receptor-binding domain (rbd) of sars-cov spike (s) protein elicits highly potent neutralizing antibody responses in the immunized animals. but it is unknown whether rbd can also induce protective immunity in an animal model, a key aspect for vaccine development. in this study, balb/c mice wer ... | 2007 | 17092615 |
| discovering severe acute respiratory syndrome coronavirus 3cl protease inhibitors: virtual screening, surface plasmon resonance, and fluorescence resonance energy transfer assays. | an integrated system has been developed for discovering potent inhibitors of severe acute respiratory syndrome coronavirus 3c-like protease (sars-cov 3cl(pro)) by virtual screening correlating with surface plasmon resonance (spr) and fluorescence resonance energy transfer (fret) technologies-based assays. the authors screened 81,287 small molecular compounds against specs database by virtual screening; 256 compounds were subsequently selected for biological evaluation. through spr technology-bas ... | 2006 | 17092912 |
| derivation of a novel sars-coronavirus replicon cell line and its application for anti-sars drug screening. | the severe acute respiratory syndrome (sars) outbreak in 2002, which had a high morbidity rate and caused worldwide alarm, remains untreated today even though sars was eventually isolated and controlled. development and high-throughput screening of efficacious drugs is therefore critical. however, currently there remains a lack of such a safe system. here, the generation and characterization of the first selectable, sars-coronavirus (sars-cov)-based replicon cell line which can be used for scree ... | 2007 | 17098272 |
| novel sars unique adomet-dependent methyltransferase. | | 2006 | 17102613 |
| severe acute respiratory syndrome coronavirus infection of mice transgenic for the human angiotensin-converting enzyme 2 virus receptor. | animal models for severe acute respiratory syndrome (sars) coronavirus infection of humans are needed to elucidate sars pathogenesis and develop vaccines and antivirals. we developed transgenic mice expressing human angiotensin-converting enzyme 2, a functional receptor for the virus, under the regulation of a global promoter. a transgenic lineage, designated ac70, was among the best characterized against sars coronavirus infection, showing weight loss and other clinical manifestations before re ... | 2007 | 17108019 |
| severe acute respiratory syndrome coronavirus open reading frame (orf) 3b, orf 6, and nucleocapsid proteins function as interferon antagonists. | the severe acute respiratory syndrome coronavirus (sars-cov) is highly pathogenic in humans, with a death rate near 10%. this high pathogenicity suggests that sars-cov has developed mechanisms to overcome the host innate immune response. it has now been determined that sars-cov open reading frame (orf) 3b, orf 6, and n proteins antagonize interferon, a key component of the innate immune response. all three proteins inhibit the expression of beta interferon (ifn-beta), and further examination rev ... | 2007 | 17108024 |
| a severe acute respiratory syndrome coronavirus that lacks the e gene is attenuated in vitro and in vivo. | a deletion mutant of severe acute respiratory syndrome coronavirus (sars-cov) has been engineered by deleting the structural e gene in an infectious cdna clone that was constructed as a bacterial artificial chromosome (bac). the recombinant virus lacking the e gene (rsars-cov-deltae) was rescued in vero e6 cells. the recovered deletion mutant grew in vero e6, huh-7, and caco-2 cells to titers 20-, 200-, and 200-fold lower than the recombinant wild-type virus, respectively, indicating that althou ... | 2007 | 17108030 |
| severe acute respiratory syndrome coronavirus protein 6 accelerates murine coronavirus infections. | one or more of the unique 3'-proximal open reading frames (orfs) of the severe acute respiratory syndrome (sars) coronavirus may encode determinants of virus virulence. a prime candidate is orf6, which encodes a 63-amino-acid membrane-associated peptide that can dramatically increase the lethality of an otherwise attenuated jhm strain of murine coronavirus (l. pewe, h. zhou, j. netland, c. tangudu, h. olivares, l. shi, d. look, t. gallagher, and s. perlman, j. virol. 79:11335-11342, 2005). to di ... | 2007 | 17108045 |
| naturally occurring anti-escherichia coli protein antibodies in the sera of healthy humans cause analytical interference in a recombinant nucleocapsid protein-based enzyme-linked immunosorbent assay for serodiagnosis of severe acute respiratory syndrome. | we reported the analytical interference of anti-escherichia coli protein (ep) antibodies in human sera and residual ep in a recombinant nucleocapsid protein-based enzyme-linked immunosorbent assay as a possible source of false positives in severe acute respiratory syndrome serodiagnosis. the rate of false positives was significantly reduced by adding mouse anti-ep antiserum in the blocking step. | 2007 | 17108287 |
| [pharmacotherapy of severe acute respiratory syndrome (sars)]. | severe acute respiratory syndrome (sars) constitutes the first new infectious disease of the current millennium. it is caused by the novel sars-coronavirus (sars-cov). sars is related to a high morbidity and mortality and first appeared during an epidemic in 2002 - 2003. to date no specific therapy against the sars-cov is available. due to the rapid spread of sars during the epidemics in 2002 - 2003, randomised and controlled multicentre studies were not performed. therefore, general guidelines ... | 2006 | 17109267 |
| radiology of severe acute respiratory syndrome (sars): the emerging pathologic-radiologic correlates of an emerging disease. | severe acute respiratory distress syndrome (sars) caused by sars-associated coronavirus (sars-cov) is a systemic infection that clinically manifests as progressive pneumonia. during the initial phases of infection the virus causes pauci-inflammatory alveolar and interstitial edema that result in imaging abnormalities dominated by ground glass opacities (ggo). severe sars cases can develop radiologic and pathologic findings of diffuse alveolar damage. although radiologic evidence of acute bronchi ... | 2006 | 17110851 |
| inhibition of sars-cov replication cycle by small interference rnas silencing specific sars proteins, 7a/7b, 3a/3b and s. | the severe acute respiratory syndrome coronavirus (sars cov) genome has 14 potential open reading frames (orfs). the first orf is translated from the full-length genomic mrna while the remaining orfs are translated from eight subgeomic rnas (sgrnas). in this study, we designed small interference rnas (sirnas) targeting sgrna 2, 3 and 7 and tested their efficiency and specificity in silencing the protein translated from the targeted sgrna. our results demonstrated that sirna 7 could inhibit sgrna ... | 2007 | 17112601 |
| characterizing 56 complete sars-cov s-gene sequences from hong kong. | the spike glycoprotein (s) gene of the severe acute respiratory syndrome-associated coronavirus (sars-cov) has been useful in analyzing the molecular epidemiology of the 2003 sars outbreaks. | 2007 | 17112780 |
| public health implications of using various case definitions in the netherlands during the worldwide sars outbreak. | this study analysed the consequences of deviation from the who case definition for the assessment of patients with suspected severe acute respiratory syndrome (sars) in the netherlands during 2003. between 17 march and 7 july 2003, as a result of dilemmas in balancing sensitivity and specificity, five different case definitions were used. the patients referred for sars assessment were analysed from a public health perspective. none of the patients referred had sars, based on serological and viro ... | 2006 | 17121628 |
| [the possible mechanism of lung injury induced by severe acute respiratory syndrome coronavirus spike glycoprotein]. | to investigate the role of severe acute respiratory syndrome coronavirus (sars-cov) in the induction of acute lung injury by promoting the synthesis of chemokine/cytokines in human endothelial cells. | 2006 | 17129463 |
| the possible origin of recent human sars coronavirus isolate from china. | | 2006 | 17131942 |
| palmitoylation of the cysteine-rich endodomain of the sars-coronavirus spike glycoprotein is important for spike-mediated cell fusion. | the sars-coronavirus (sars-cov) is the etiological agent of the severe acute respiratory syndrome (sars). the sars-cov spike (s) glycoprotein mediates membrane fusion events during virus entry and virus-induced cell-to-cell fusion. the cytoplasmic portion of the s glycoprotein contains four cysteine-rich amino acid clusters. individual cysteine clusters were altered via cysteine-to-alanine amino acid replacement and the modified s glycoproteins were tested for their transport to cell-surfaces an ... | 2007 | 17134730 |
| porcine innate and adaptative immune responses to influenza and coronavirus infections. | both innate and adaptative immune responses contribute to the control of infectious diseases, including by limiting the spreading of zoonotic diseases from animal reservoirs to humans. pigs represent an important animal reservoir for influenza virus infection of human populations and are also naturally infected by coronaviruses, an important group of viruses, which includes the recently emerged severe acute respiratory syndrome (sars) virus. studies on both innate and adaptative immune responses ... | 2006 | 17135502 |
| generating vesicular stomatitis virus pseudotype bearing the severe acute respiratory syndrome coronavirus spike envelope glycoprotein for rapid and safe neutralization test or cell-entry assay. | we generated a recombinant vesicular stomatitis virus (vsv) pseudotype (vsv delta g*sg) by replacing the envelope g gene with the gfp gene and complementing with spike glycoprotein (s) of sars-cov in trans. the neutralization and infection blocking tests showed that the vsv delta g*sg and sars-cov reacted similarly to sars-cov specific antiserum, suggesting the vsvdelta g*sg can be a safe replacement of the live sars-cov for neutralization test and cell-entry assay. | 2006 | 17135519 |
| inhibition of sars-cov gene expression by adenovirus-delivered small hairpin rna. | severe acute respiratory syndrome (sars) is a highly contagious and lethal disease caused by a new type of coronavirus, sars-associated coronavirus (sars-cov). currently, there is no efficient treatment and prevention for this disease. we constructed recombinant adenoviral vectors that can express shrnas, which inhibited the expression of sars-cov genes effectively in mammalian cells. | 2007 | 17139181 |
| augmentation of chemokine production by severe acute respiratory syndrome coronavirus 3a/x1 and 7a/x4 proteins through nf-kappab activation. | severe acute respiratory syndrome (sars) is characterized by rapidly progressing respiratory failure resembling acute/adult respiratory distress syndrome (ards) associated with uncontrolled inflammatory responses. here, we demonstrated that, among five accessory proteins of sars coronavirus (sars-cov) tested, 3a/x1 and 7a/x4 were capable of activating nuclear factor kappa b (nf-kappab) and c-jun n-terminal kinase (jnk), and significantly enhanced interleukin 8 (il-8) promoter activity. furthermo ... | 2006 | 17141229 |
| genetic distance of sars coronavirus from the recent natural case. | phylogenetic analysis of sars coronavirus isolates based on the spike gene and protein sequence using neighbor-joining, maximum likelihood and bayesian inference methods indicated that a recent human sars-cov isolate was closer to some human sars-cov isolates from earlier epidemic phase than to the sars-cov-like viruses isolated from wild animals during previous epidemic phase. a reasonable judgment based on phylogenetic relationship and sequence variations it is likely that the recent human sar ... | 2007 | 17141432 |
| molecular pathogenesis of severe acute respiratory syndrome. | the global outbreak in 2002-2003 of severe acute respiratory syndrome (sars) posed a serious threat to public health and had a significant impact on socioeconomic stability. although the global outbreak of sars has been contained, there are serious concerns over its re-emergence and bioterrorism potential, and up to date, no specific treatment exists for this disease. here we review the progress of studies on the pathogenesis of the disease, in particular, studies on the molecular level. | 2007 | 17142081 |
| reversible unfolding of the severe acute respiratory syndrome coronavirus main protease in guanidinium chloride. | chemical denaturant sensitivity of the dimeric main protease from severe acute respiratory syndrome (sars) coronavirus to guanidinium chloride was examined in terms of fluorescence spectroscopy, circular dichroism, analytical ultracentrifuge, and enzyme activity change. the dimeric enzyme dissociated at guanidinium chloride concentration of <0.4 m, at which the enzymatic activity loss showed close correlation with the subunit dissociation. further increase in guanidinium chloride induced a rever ... | 2007 | 17142288 |
| sars cov main proteinase: the monomer-dimer equilibrium dissociation constant. | the sars coronavirus main proteinase (sars cov main proteinase) is required for the replication of the severe acute respiratory syndrome coronavirus (sars cov), the virus that causes sars. one function of the enzyme is to process viral polyproteins. the active form of the sars cov main proteinase is a homodimer. in the literature, estimates of the monomer-dimer equilibrium dissociation constant, kd, have varied more than 65,0000-fold, from <1 nm to more than 200 microm. because of these discrepa ... | 2006 | 17144656 |
| progressive docking: a hybrid qsar/docking approach for accelerating in silico high throughput screening. | a combination of protein-ligand docking and ligand-based qsar approaches has been elaborated, aiming to speed-up the process of virtual screening. in particular, this approach utilizes docking scores generated for already processed compounds to build predictive qsar models that, in turn, assess hypothetical target binding affinities for yet undocked entries. the "progressive docking" has been tested on drug-like substances from the nci database that have been docked into several unrelated target ... | 2006 | 17149875 |
| anti-sars-cov activity of nucleoside analogs having 6-chloropurine as a nucleobase. | nucleoside analogs that have 6-chloropurine as a nucleobase were synthesized and evaluated to develop novel anti-sars-cov agents. two compounds among them showed promising activity that was comparable to mizoribine and ribavirin. moreover, one of the compounds showed a structurally unique property. | 2006 | 17150843 |
| participation of both host and virus factors in induction of severe acute respiratory syndrome (sars) in f344 rats infected with sars coronavirus. | to understand the pathogenesis and develop an animal model of severe acute respiratory syndrome (sars)-associated coronavirus (sars-cov), the frankfurt 1 sars-cov isolate was passaged serially in young f344 rats. young rats were susceptible to sars-cov but cleared the virus rapidly within 3 to 5 days of intranasal inoculation. after 10 serial passages, replication and virulence of sars-cov were increased in the respiratory tract of young rats without clinical signs. by contrast, adult rats infec ... | 2007 | 17151094 |
| long-range cooperative interactions modulate dimerization in sars 3clpro. | severe acute respiratory syndrome (sars) is an infectious disease caused by the human coronavirus, sars-cov. the main viral protease, sars 3clpro, is a validated target for the development of antiviral therapies. since the enzyme is a homodimer and the individual monomers are inactive, two approaches are being used to develop inhibitors: enzyme activity inhibitors that target the active site and dimerization inhibitors. dimerization inhibitors are usually targeted to the dimerization interface a ... | 2006 | 17154528 |
| microarray-in-a-tube for detection of multiple viruses. | the detection of multiple viruses is important for pathogenic diagnosis and disease control. microarray detection is a good method, but requires complex procedures for multiple virus detection. | 2007 | 17158198 |
| generation and characterization of human monoclonal neutralizing antibodies with distinct binding and sequence features against sars coronavirus using xenomouse. | passive therapy with neutralizing human monoclonal antibodies (mabs) could be an effective therapy against severe acute respiratory syndrome coronavirus (sars-cov). utilizing the human immunoglobulin transgenic mouse, xenomouse, we produced fully human sars-cov spike (s) protein specific antibodies. antibodies were examined for reactivity against a recombinant s1 protein, to which 200 antibodies reacted. twenty-seven antibodies neutralized 200tcid(50) sars-cov (urbani). additionally, 57 neutrali ... | 2007 | 17161858 |
| [severe acute respiratory syndrome]. | towards the end of 2002 it was the epidemic'outbreak of very severe atypical pneumonia of unknown cause. 32 countries were affected. during 7 months about 8000 cases and 900 fatalities were reported. world health organization defined the new disease as severe acute respiratory syndrome (sars). thanks to the international investigations the etiologic factor of the disease was quickly identified. new coronavirus was described. it allowed the introduction of new more effective methods of disease' i ... | 2006 | 17163178 |
| the lesson of supplementary treatment with chinese medicine on severe laboratory-confirmed sars patients. | chinese medicine (cm) has been used to control infectious diseases for thousands of years. in 2003 outbreaks of severe acute respiratory syndrome (sars) occurred in china, hong kong and taiwan. in view of the possible beneficial effect of cm on sars, we conducted this study to examine whether cm is of any benefit as a supplementary treatment of sars. four severe laboratory-confirmed sars patients received routine western-medicine treatment plus different supplementary treatment: cm a, cm b and c ... | 2006 | 17163582 |
| symptom combinations associated with outcome and therapeutic effects in a cohort of cases with sars. | severe acute respiratory syndrome (sars) is an infectious disease and some of its symptoms were clinically indistinguishable of those from similar diseases. this study aimed to find the symptom combinations associated with adverse outcome and the therapeutic effects in a cohort of patients with probable sars retrospectively. in 2003, 123 sars cases in beijing were subjected to a strictly western medicine (wm) treatment, or a combined treatment (wm plus herba houttuyniae injection, addition of in ... | 2006 | 17163583 |
| the cytoplasmic tail of the severe acute respiratory syndrome coronavirus spike protein contains a novel endoplasmic reticulum retrieval signal that binds copi and promotes interaction with membrane protein. | like other coronaviruses, severe acute respiratory syndrome coronavirus (sars cov) assembles at and buds into the lumen of the endoplasmic reticulum (er)-golgi intermediate compartment (ergic). accumulation of the viral envelope proteins at this compartment is a prerequisite for virus assembly. previously, we reported the identification of a dibasic motif (kxhxx) in the cytoplasmic tail of the sars cov spike (s) protein that was similar to a canonical dilysine er retrieval signal. here we demons ... | 2007 | 17166901 |
| an overall picture of sars coronavirus (sars-cov) genome-encoded major proteins: structures, functions and drug development. | a severe atypical pneumonia designated as severe acute respiratory syndrome (sars) by the world health organization broke out in china and menaced to more than other 30 countries between the end of the year 2002 and june of the year 2003. a novel coronavirus called severe acute respiratory syndrome coronavirus (sars-cov) has been recently identified as the etiological agent responsible for the infectious sars disease. based on extensively scientific cooperation and almost two-year's studies, rem ... | 2006 | 17168760 |
| quaternary structure, substrate selectivity and inhibitor design for sars 3c-like proteinase. | the sars coronavirus 3c-like proteinase is recognized as a potential drug design target for the treatment of severe acute respiratory syndrome. in the past few years, much work has been done to understand the catalytic mechanism of this target protein and to design its selective inhibitors. the protein exists as a dimer/monomer mixture in solution and the dimer was confirmed to be the active species for the enzyme reaction. quantitative dissociation constants have been reported for the dimer by ... | 2006 | 17168761 |
| bioinformatics research on the sars coronavirus (sars_cov) in china. | severe acute respiratory syndrome (sars) first appeared in 2002 in china, which fastly affected about 8000 patients over 29 countries and caused 774 fatalities. as its pathogen was identified as a new kind of coronavirus (sars_cov), its genome was quickly sequenced on several isolates. studies on its functional genomics were performed by combinatorial application of all the available bioinformatics tools and the development of new programs. in this way, it was found that the four proteins were a ... | 2006 | 17168762 |
| drug design targeting the main protease, the achilles' heel of coronaviruses. | coronaviruses (covs), a genus containing about 26 known species to date, cause highly prevalent diseases and are often severe or fatal in humans and animals. in 2003, a previously unknown coronavirus was identified to be the etiological agent of a global outbreak of a form of life-threatening pneumonia called severe acute respiratory syndrome (sars). no efficacious therapy is currently available, and vaccines and drugs are under development to prevent sars-cov infection in many countries. the co ... | 2006 | 17168763 |
| progress in computational approach to drug development against sars. | since the outbreak of sars (severe acute respiratory syndrome) in november 2002 in southern china's guangdong province, considerable progress has been made in the development of drugs for sars therapy. the present mini review is focused on the area of computer-aided drug discovery, i.e., the advances achieved mainly from the approaches of structural bioinformatics, pharmacophore modeling, molecular docking, peptide-cleavage site prediction, and other computational means. it is highlighted that t ... | 2006 | 17168850 |
| [severe acute respiratory syndrome (sars)]. | the sudden appearance of the severe acute respiratory syndrome (sars) in 2003 demonstrated to the world at large that despite the high standard of medical care in affected countries, a highly contagious emerging infectious disease could spread rapidly worldwide. by application and improvement of stringent infection control measures, a further spread of sars could be stopped and the disease could so far be defeated. in the meantime, decisive progress in the knowledge about the structure and furth ... | 2006 | 17171319 |
| core structure of s2 from the human coronavirus nl63 spike glycoprotein. | human coronavirus nl63 (hcov-nl63) has recently been identified as a causative agent of acute respiratory tract illnesses in infants and young children. the hcov-nl63 spike (s) protein mediates virion attachment to cells and subsequent fusion of the viral and cellular membranes. this viral entry process is a primary target for vaccine and drug development. hcov-nl63 s is expressed as a single-chain glycoprotein and consists of an n-terminal receptor-binding domain (s1) and a c-terminal transmemb ... | 2006 | 17176042 |
| evaluation of immunomodulators, interferons and known in vitro sars-cov inhibitors for inhibition of sars-cov replication in balb/c mice. | compounds approved for therapeutic use and in vitro inhibitors of severe acute respiratory syndrome coronavirus (sars-cov) were evaluated for inhibition in the mouse sars-cov replication model. a hybrid interferon, interferon alpha (ifn-alpha) b/d, and a mismatched double-stranded (ds) rna interferon (ifn) inducer, ampligen (poly i:poly c124), were the only compounds that potently inhibited virus titres in the lungs of infected mice as assessed by cpe titration assays. when mice were dosed intra ... | 2006 | 17176632 |
| antiviral activity of nucleoside analogues against sars-coronavirus (sars-cov). | the recent outbreak of severe acute respiratory syndrome (sars), which is an acute respiratory illness, is caused by newly discovered sars coronavirus (sars-cov). herein we describe the antiviral activity of several classes of nucleoside analogues evaluated against sars-cov in vero 76 cells, some of which exhibited moderate activity. | 2006 | 17176633 |
| coupling molecular beacons to barcoded metal nanowires for multiplexed, sealed chamber dna bioassays. | we have combined molecular beacon (mb) probes with barcoded metal nanowires to enable no-wash, sealed chamber, multiplexed detection of nucleic acids. probe design and experimental parameters important in nanowire-based mb assays are discussed. loop regions of 24 bases and 5 base pair stem regions in the beacon probes gave optimal performance. our results suggest that thermodynamic predictions for secondary structure stability of solution-phase mb can guide probe design for nanowire-based assays ... | 2006 | 17177440 |
| the psychological effect of severe acute respiratory syndrome on emergency department staff. | the severe acute respiratory syndrome (sars) outbreak in 2003 affected 29 countries. the sars outbreak was unique in its rapid transmission and it resulted in heavy stress in first-line healthcare workers, particularly in the emergency department. | 2007 | 17183035 |
| long-term persistence of robust antibody and cytotoxic t cell responses in recovered patients infected with sars coronavirus. | most of the individuals infected with sars coronavirus (sars-cov) spontaneously recovered without clinical intervention. however, the immunological correlates associated with patients' recovery are currently unknown. in this report, we have sequentially monitored 30 recovered patients over a two-year period to characterize temporal changes in sars-cov-specific antibody responses as well as cytotoxic t cell (ctl) responses. we have found persistence of robust antibody and ctl responses in all of ... | 2006 | 17183651 |
| baculovirus surface display of sars coronavirus (sars-cov) spike protein and immunogenicity of the displayed protein in mice models. | the baculovirus surface display technique has provided an ideal tool to display foreign proteins with natural conformation, functions, and immunogenicity. in this work, we explored the application of this technique on sars-associated coronavirus (sars-cov) spike (s) protein, and further analyzed the immunogenicity of displayed s protein. the entire ectodomain of s protein was fused between the gp64 signal peptide and the vsv-g membrane anchor and successfully displayed on the baculovirus surface ... | 2006 | 17184168 |
| public health awareness of emerging zoonotic viruses of bats: a european perspective. | bats classified in the order chiroptera are the most abundant and widely distributed non-human mammalian species in the world. several bat species are reservoir hosts of zoonotic viruses and therefore can be a public health hazard. lyssaviruses of different genotypes have emerged from bats in america (genotype 1 rabies virus; rabv), europe (european bat lyssavirus; eblv), and australia (australian bat lyssavirus; ablv), whereas nipah virus is the most important recent zoonosis of bat origin in a ... | 2006 | 17187565 |
| public health awareness of emerging zoonotic viruses of bats: a european perspective. | bats classified in the order chiroptera are the most abundant and widely distributed non-human mammalian species in the world. several bat species are reservoir hosts of zoonotic viruses and therefore can be a public health hazard. lyssaviruses of different genotypes have emerged from bats in america (genotype 1 rabies virus; rabv), europe (european bat lyssavirus; eblv), and australia (australian bat lyssavirus; ablv), whereas nipah virus is the most important recent zoonosis of bat origin in a ... | 2006 | 17187565 |
| expression, purification and characterization of recombinant severe acute respiratory syndrome coronavirus non-structural protein 1. | the coronavirus (cov) responsible for severe acute respiratory syndrome (sars), sars-cov, encodes two large polyproteins (pp1a and pp1ab) that are processed by two viral proteases to yield mature non-structural proteins (nsps). many of these nsps have essential roles in viral replication, but several have no assigned function and possess amino acid sequences that are unique to the cov family. one such protein is sars-cov nsp1, which is processed from the n-terminus of both pp1a and pp1ab. the ma ... | 2007 | 17187987 |
| production of authentic sars-cov m(pro) with enhanced activity: application as a novel tag-cleavage endopeptidase for protein overproduction. | the viral proteases have proven to be the most selective and useful for removing the fusion tags in fusion protein expression systems. as a key enzyme in the viral life-cycle, the main protease (m(pro)) is most attractive for drug design targeting the sars coronavirus (sars-cov), the etiological agent responsible for the outbreak of severe acute respiratory syndrome (sars) in 2003. in this study, sars-cov m(pro) was used to specifically remove the gst tag in a new fusion protein expression syste ... | 2007 | 17189639 |
| the synergistic interaction of interferon types i and ii leads to marked reduction in severe acute respiratory syndrome-associated coronavirus replication and increase in the expression of mrnas for interferon-induced proteins. | interferon (ifn)-alpha, -beta and -gamma have been shown to be only marginally effective against severe acute respiratory syndrome coronavirus (sars-cov) replication in vero cell lines. we investigated the combination of type i ifns (ifn-alpha or -beta) and ifn-gamma for antiviral activity and found that such combinations synergistically inhibited sars-cov replication in vero cells, using yield reduction assay and the isobologram and combination index methods of chou and talalay for evaluation. ... | 2007 | 17191018 |
| vaccine efficacy in senescent mice challenged with recombinant sars-cov bearing epidemic and zoonotic spike variants. | in 2003, severe acute respiratory syndrome coronavirus (sars-cov) was identified as the etiological agent of severe acute respiratory syndrome, a disease characterized by severe pneumonia that sometimes results in death. sars-cov is a zoonotic virus that crossed the species barrier, most likely originating from bats or from other species including civets, raccoon dogs, domestic cats, swine, and rodents. a sars-cov vaccine should confer long-term protection, especially in vulnerable senescent pop ... | 2006 | 17194199 |
| vaccine efficacy in senescent mice challenged with recombinant sars-cov bearing epidemic and zoonotic spike variants. | in 2003, severe acute respiratory syndrome coronavirus (sars-cov) was identified as the etiological agent of severe acute respiratory syndrome, a disease characterized by severe pneumonia that sometimes results in death. sars-cov is a zoonotic virus that crossed the species barrier, most likely originating from bats or from other species including civets, raccoon dogs, domestic cats, swine, and rodents. a sars-cov vaccine should confer long-term protection, especially in vulnerable senescent pop ... | 2006 | 17194199 |
| lipid rafts play an important role in the early stage of severe acute respiratory syndrome-coronavirus life cycle. | lipid rafts are involved in the life cycle of many viruses. in this study, we showed that lipid rafts also play an important role in the life cycle of severe acute respiratory syndrome (sars)-coronavirus (cov). cholesterol depletion by pretreatment of vero e6 cells with methyl-beta-cyclodextrin (mbetacd) inhibited the production of sars-cov particles released from the infected cells. this inhibition was prevented by addition of cholesterol to the culture medium, indicating that the reduction of ... | 2007 | 17194611 |
| severe acute respiratory syndrome in children. | severe acute respiratory syndrome (sars) is a febrile, respiratory tract illness caused by infection with the newly identified sars-associated coronavirus. a notable feature of the 2003 global sars outbreak was the relative paucity of cases reported among children. we reviewed the epidemiologic and clinical features of sars in children and discuss implications of these findings for diagnosis, treatment and prevention of sars. | 2007 | 17195709 |
| crystal structures reveal an induced-fit binding of a substrate-like aza-peptide epoxide to sars coronavirus main peptidase. | the sars coronavirus main peptidase (sars-cov m(pro)) plays an essential role in the life-cycle of the virus and is a primary target for the development of anti-sars agents. here, we report the crystal structure of m(pro) at a resolution of 1.82 angstroms, in space group p2(1) at ph 6.0. in contrast to the previously reported structure of m(pro) in the same space group at the same ph, the active sites and the s1 specificity pockets of both protomers in the structure of m(pro) reported here are i ... | 2007 | 17196984 |
| development and validation of a high-throughput screen for inhibitors of sars cov and its application in screening of a 100,000-compound library. | the authors have developed a high-throughput screen (hts) that allows for the identification of potential inhibitors of the severe acute respiratory syndrome coronavirus (sars cov) from large compound libraries. the luminescent-based assay measures the inhibition of sars cov-induced cytopathic effect (cpe) in vero e6 cells. the assay was validated in 96-well plates in a bsl3 containment facility. the assay is sensitive and robust, with z values > 0.6, signal to background (s/b) > 16, and signal ... | 2007 | 17200104 |
| novel beta-barrel fold in the nuclear magnetic resonance structure of the replicase nonstructural protein 1 from the severe acute respiratory syndrome coronavirus. | the nonstructural protein 1 (nsp1) of the severe acute respiratory syndrome coronavirus has 179 residues and is the n-terminal cleavage product of the viral replicase polyprotein that mediates rna replication and processing. the specific function of nsp1 is not known. here we report the nuclear magnetic resonance structure of the nsp1 segment from residue 13 to 128, which represents a novel alpha/beta-fold formed by a mixed parallel/antiparallel six-stranded beta-barrel, an alpha-helix covering ... | 2007 | 17202208 |
| recombinant truncated nucleocapsid protein as antigen in a novel immunoglobulin m capture enzyme-linked immunosorbent assay for diagnosis of severe acute respiratory syndrome coronavirus infection. | we report the development of an immunoglobulin m (igm) antibody capture enzyme-linked immunosorbent assay (mac-elisa) for severe acute respiratory syndrome coronavirus (sars-cov) by using recombinant truncated sars-cov nucleocapsid protein as the antigen. the newly developed mac-elisa had a specificity and sensitivity of 100% as evaluated by using sera from healthy volunteers and patients with laboratory-confirmed sars. using serial serum samples collected from sars patients, the times to seroco ... | 2007 | 17202310 |
| unique sars-cov protein nsp1: bioinformatics, biochemistry and potential effects on virulence. | viruses have evolved a myriad of strategies for promoting viral replication, survival and spread. sequence analysis of the severe acute respiratory syndrome coronavirus (sars-cov) genome predicts several proteins that are unique to sars-cov. the search to understand the high virulence of sars-cov compared with related coronaviruses, which cause lesser respiratory illnesses, has recently focused on the unique nsp1 protein of sars-cov and suggests evolution of a possible new virulence mechanism in ... | 2007 | 17207625 |
| the intracellular sites of early replication and budding of sars-coronavirus. | in this study, we analyzed the replication and budding sites of severe acute respiratory syndrome coronavirus (sars-cov) at early time points of infection. we detected cytoplasmic accumulations containing the viral nucleocapsid protein, viral rna and the non-structural protein nsp3. using em techniques, we found that these putative viral replication sites were associated with characteristic membrane tubules and double membrane vesicles that most probably originated from er cisternae. in addition ... | 2007 | 17210170 |
| features discriminating sars from other severe viral respiratory tract infections. | this study investigated the discriminatory features of severe acute respiratory syndrome (sars) and severe non-sars community-acquired viral respiratory infection (requiring hospitalization) in an emergency department in hong kong. in a case-control study, clinical, laboratory and radiological data from 322 patients with laboratory-confirmed sars from the 2003 sars outbreak were compared with the data of 253 non-sars adult patients with confirmed viral respiratory tract infection from 2004 in or ... | 2007 | 17219094 |
| a mouse-adapted sars-coronavirus causes disease and mortality in balb/c mice. | no single animal model for severe acute respiratory syndrome (sars) reproduces all aspects of the human disease. young inbred mice support sars-coronavirus (sars-cov) replication in the respiratory tract and are available in sufficient numbers for statistical evaluation. they are relatively inexpensive and easily accessible, but their use in sars research is limited because they do not develop illness following infection. older (12- to 14-mo-old) balb/c mice develop clinical illness and pneumoni ... | 2007 | 17222058 |
| utility of the aged balb/c mouse model to demonstrate prevention and control strategies for severe acute respiratory syndrome coronavirus (sars-cov). | the causative agent of severe acute respiratory syndrome (sars) was identified as a coronavirus (cov) following the outbreak of 2002-2003. there are currently no licensed vaccines or treatments for sars-cov infections. potential prevention and control strategies that show promise in vitro must be evaluated in animal models. the aged balb/c mouse model for sars supports a high level of viral replication in association with clinical illness and disease that mimics sars in the elderly. we tested tw ... | 2007 | 17227689 |
| ribonucleocapsid formation of severe acute respiratory syndrome coronavirus through molecular action of the n-terminal domain of n protein. | conserved among all coronaviruses are four structural proteins: the matrix (m), small envelope (e), and spike (s) proteins that are embedded in the viral membrane and the nucleocapsid phosphoprotein (n), which exists in a ribonucleoprotein complex in the lumen. the n-terminal domain of coronaviral n proteins (n-ntd) provides a scaffold for rna binding, while the c-terminal domain (n-ctd) mainly acts as oligomerization modules during assembly. the c terminus of the n protein anchors it to the vir ... | 2007 | 17229691 |
| generic detection of coronaviruses and differentiation at the prototype strain level by reverse transcription-pcr and nonfluorescent low-density microarray. | a nonfluorescent low-cost, low-density oligonucleotide array was designed for detecting the whole coronavirus genus after reverse transcription (rt)-pcr. the limit of detection was 15.7 copies/reaction. the clinical detection limit in patients with severe acute respiratory syndrome was 100 copies/sample. in 39 children suffering from coronavirus 229e, nl63, oc43, or hku1, the sensitivity was equal to that of individual real-time rt-pcrs. | 2007 | 17229859 |
| recombinant protein-based assays for detection of antibodies to severe acute respiratory syndrome coronavirus spike and nucleocapsid proteins. | recombinant severe acute respiratory syndrome (sars) nucleocapsid and spike protein-based immunoglobulin g immunoassays were developed and evaluated. our assays demonstrated high sensitivity and specificity to the sars coronavirus in sera collected from patients as late as 2 years postonset of symptoms. these assays will be useful not only for routine sars coronavirus diagnostics but also for epidemiological and antibody kinetic studies. | 2007 | 17229882 |
| impact of severe acute respiratory syndrome care on the general health status of healthcare workers in taiwan. | the impact of the outbreak of severe acute respiratory syndrome (sars) was enormous, but few studies have focused on the infectious and general health status of healthcare workers (hcws) who treated patients with sars. | 2007 | 17230391 |
| evidence for quasi species in severe acute respiratory syndrome-associated coronavirus deletion mutants. | | 2007 | 17230423 |
| characterization of the cleavage of signal peptide at the c-terminus of hepatitis c virus core protein by signal peptide peptidase. | production of hepatitis c virus (hcv) core protein requires the cleavages of polyprotein by signal peptidase and signal peptide peptidase (spp). cleavage of signal peptide at the c-terminus of hcv core protein by spp was characterized in this study. the spko mutant (mutate a.a. 189-193 from asayq to ppfpf) is more efficient than the a/f mutant (mutate a.a 189 and 191 from a to f) in blocking the cleavage of signal peptide by signal peptidase. the cleavage efficiency of spp is inversely proportio ... | 2007 | 17237979 |
| development of a method for bacteria and virus recovery from heating, ventilation, and air conditioning (hvac) filters. | the aim of the work presented here is to study the effectiveness of building air handling units (ahus) in serving as high volume sampling devices for airborne bacteria and viruses. an hvac test facility constructed according to ashrae standard 52.2-1999 was used for the controlled loading of hvac filter media with aerosolized bacteria and virus. nonpathogenic bacillus subtilis var. niger was chosen as a surrogate for bacillus anthracis. three animal viruses; transmissible gastroenteritis virus ( ... | 2006 | 17240906 |
| the immunobiology of sars*. | severe acute respiratory syndrome (sars) presented as an atypical pneumonia that progressed to acute respiratory distress syndrome in approximately 20% of cases and was associated with a mortality of about 10%. the etiological agent was a novel coronavirus (cov). angiotensin-converting enzyme 2 is the functional receptor for sars-cov; dc-sign and cd209l (l-sign) can enhance viral entry. although the virus infects the lungs, gastrointestinal tract, liver, and kidneys, the disease is limited to th ... | 2007 | 17243893 |
| [avian influenza and the severe acute respiratory syndrome (sars) - experiences and perspectives]. | new respiratory viruses associated with pneumonia have in the past few years been detected in humans. the sudden appearance of the severe acute respiratory syndrome (sars) in 2003 demonstrated that an emerging and highly infectious disease caused by a hitherto unknown virus was able to spread rapidly, but could finally be contained by stringent measures. the avian influenza a-h5n1-virus of high pathogenicity has crossed in multiple instances the species barriers between humans, mammals, and bird ... | 2007 | 17253209 |
| molecular pathology in the lungs of severe acute respiratory syndrome patients. | severe acute respiratory syndrome (sars) is a novel infectious disease with disastrous clinical consequences, in which the lungs are the major target organs. previous studies have described the general pathology in the lungs of sars patients and have identified some of the cell types infected by sars coronavirus (sars-cov). however, at the time of this writing, there were no comprehensive reports of the cellular distribution of the virus in lung tissue. in this study, we have performed double la ... | 2007 | 17255322 |
| comparative immunization in balb/c mice with recombinant replication-defective adenovirus vector and dna plasmid expressing a sars-cov nucleocapsid protein gene. | in order to investigate immunogenicity in the induction of humoral and cellular immune responses, severe acute respiratory syndrome associated coronavirus (sars-cov)-n gene recombinant replication-defective adenoviral vector, rad-n, was generated and immunized balb/c mice in a pcdna3.1-n prime-rad-n boost regimen. after humoral and cellular immune response detection, different levels of sars-cov n protein specific antibodies and interferon-gamma (ifn-gamma) secretion are shown compared to contro ... | 2006 | 17257500 |
| [lessons from sars]. | given that viruses may not have adapted to human-to-human transmission during their initial emergence in humans, they may thus be easier to control; accordingly, early detection by surveillance of unusual outbreaks is essential. our healthcare systems are very vulnerable to viruses with a particular tropism for hospital personnel. international collaboration by teams of epidemiologists as well as virologists was the key to success against sars (severe acute respiratory syndrome). we were lucky i ... | 2007 | 17258678 |
| exosomal vaccines containing the s protein of the sars coronavirus induce high levels of neutralizing antibodies. | infection with the sars-associated coronavirus (sars-cov) induces an atypical pulmonary disease with a high lethality rate. although the initial sars epidemic was contained, sporadic outbreaks of the disease still occur, suggesting a continuous need for a vaccine against this virus. we therefore explored exosome-based vaccines containing the spike s proteins of sars-cov. s-containing exosomes were obtained by replacing the transmembrane and cytoplasmic domains of the s protein by those of vsv-g. ... | 2007 | 17258782 |
| establishment of a reference panel for the detection of anti-sars-cov antibodies. | the immunological assays for detection of antibodies against sars-cov were developed in-house and some of them are available commercially. however, the antigens used in these assays differed. in order to validate the reliability of these assays, the standard panel should be established. in this study, we have expressed and purified severe acute respiratory syndrome (sars) structural proteins and their fragments and developed indirect enzyme-linked immunosorbent assays (elisas) that detect antibo ... | 2007 | 17261372 |
| rnai therapeutics: can sirnas conquer sars? | | 2006 | 17262907 |
| trends in the development and approval of monoclonal antibodies for viral infections. | monoclonal antibodies (mabs) developed for either the prevention or treatment of viral diseases represent a small, but valuable, class of products. since 1985, commercial firms have initiated clinical studies involving a total of 28 mabs. to date, one product (palivizumab) has been approved and eight candidates are currently in clinical study. most commercial mabs studied as antiviral agents in the clinic have either directly or indirectly targeted human immunodeficiency virus, respiratory syncy ... | 2007 | 17263584 |
| children's vaccines do not induce cross reactivity against sars-cov. | in contrast with adults, children infected by severe acute respiratory syndrome-corona virus (sars-cov) develop milder clinical symptoms. because of this, it is speculated that children vaccinated with various childhood vaccines might develop cross immunity against sars-cov. antisera and t cells from mice immunised with various vaccines were used to determine whether they developed cross reactivity against sars-cov. the results showed no marked cross reactivity against sars-cov, which implies th ... | 2007 | 17264247 |
| inhibitor design for sars coronavirus main protease based on "distorted key theory". | in order to find effective peptide inhibitors against sars cov m(pro), an analysis was performed for 11 oligo-peptides that can be cleaved by the sars coronavirus main protease (cov m(pro), or 3cl(pro)). flexible molecular alignments of the 11 cleavable peptides have provided useful insights into the chemical properties of their amino acid residues close to the cleavage site. moreover, it was found through the ligand-receptor docking studies that of the 11 cleavable peptides, nh2-atlq / aias-coo ... | 2007 | 17266617 |
| spike protein of sars-cov stimulates cyclooxygenase-2 expression via both calcium-dependent and calcium-independent protein kinase c pathways. | we have previously shown that the nucleocapsid protein of sars-associated coronavirus (sars-cov) activated cyclooxygenase-2 (cox-2) expression. in this study, we identified another viral protein, the spike of sars-cov, which played an important role in virus-stimulated cox-2 expression after screening all genes from the sars-cov genome. we found that an upstream calcium-dependent pkc isozyme pkc alpha that modulates the downstream erk/nf-kappab pathway through an influx of extracellular ca2+ is ... | 2007 | 17267381 |
| evolutionary insights into the ecology of coronaviruses. | although many novel members of the coronaviridae have recently been recognized in different species, the ecology of coronaviruses has not been established. our study indicates that bats harbor a much wider diversity of coronaviruses than any other animal species. dating of different coronavirus lineages suggests that bat coronaviruses are older than those recognized in other animals and that the human severe acute respiratory syndrome (sars) coronavirus was directly derived from viruses from wil ... | 2007 | 17267506 |
| inhibition of infection caused by severe acute respiratory syndrome-associated coronavirus by equine neutralizing antibody in aged mice. | the high susceptibility of elderly to severe acute respiratory syndrome-associated coronavirus (sars-cov) indicates how crucial it is to protect the elderly by various strategies. aged balb/c mice displayed a high susceptibility to sars-cov and have been a valuable platform for evaluation of strategies against sars-cov infection. in this study, we confirmed the validity of this model using various methods, and verified that equine anti-sars-cov f(ab')(2) can prevent aged animals from sars-cov in ... | 2007 | 17276898 |
| enhancement of cytotoxicity against vero e6 cells persistently infected with sars-cov by mycoplasma fermentans. | we previously reported that cells with persistent severe acute respiratory syndrome coronavirus (sars-cov) infection were established after apoptotic events. in the present study, we investigated the cytopathic effects of dual infection with sars-cov and mycoplasma fermentans on vero e6 cells. dual infection completely killed cells and prevented the establishment of persistent sars-cov infection. m. fermentans induced inhibition of cell proliferation, but the cells remained alive. apoptosis was ... | 2007 | 17277901 |
| pathogenesis of avian flu h5n1 and sars. | avian influenza a (h5n1) and severe acute respiratory syndrome (sars) coronavirus are infections that cause a severe viral pneumonia leading to acute respiratory dysfunction syndrome and carry a high case-fatality rate. we have investigated innate immune responses to both viruses using primary human macrophages and respiratory epithelial cells as in vitro models. in contrast to human influenza a h1ni viruses, the h5n1 viruses hyper-induce cytokines (tumour necrosis factor [tnf]alpha, interferon ... | 2006 | 17278385 |
| the 3a protein of sars-coronavirus induces apoptosis in vero e6 cells. | an outbreak of severe acute respiratory syndrome (sars) occurred in china and the first case emerged in mid november 2002. the etiologic agent of this disease was found to be a previously unknown coronavirus, sars-cov. the detailed pathology of sars-cov infection and the host response to the viral infection are still not known. the 3a gene encodes a non-structural viral protein which is predicted to be a transmembrane protein. in this study, we showed that the 3a protein was localized to the end ... | 2005 | 17282011 |
| investigation of interactions between two monoclonal antibodies and sars virus with a label-free protein array. | the investigation of interactions between two kinds of monoclonal antibodies and sars virus with a label-free protein array technique were presented in this paper. the performance consists of three parts: a surface modification for ligand immobilization/surface, a protein array fabrication with an integrated microfluidic system for patterning, packaging and liquid handling, and a protein array reader of imaging ellipsometer. this revealed the technique could be used as an immunoassay for qualita ... | 2005 | 17282435 |
| [expression of predicted b cell epitope peptide in s2 subunit of sars coronavirus spike protein in e.coli and identification of its mimic antigenicity]. | to study the expression of predicted b cell epitope peptide in s2 subunit of sars coronavirus spike protein in e.coli and its mimic antigenicity to s2 protein. | 2007 | 17286901 |
| development of vaccines and passive immunotherapy against sars corona virus using scid-pbl/hu mouse models. | we have investigated novel vaccine strategies against severe acute respiratory syndrome (sars) cov using cdna constructs encoding the structural antigens: (s), (m), (e), or (n) protein, derived from sars cov. pbl from healthy human volunteers were administered i.p. into il-2 receptor gamma-chain disrupted scid mice, and scid-pbl/hu mice were constructed. these mice can be used to analyze the human immune response in vivo. sars m dna vaccine and n dna vaccine induced human ctl specific for sars c ... | 2007 | 17289225 |
| the potential of targeted antibody prophylaxis in sars outbreak control: a mathematic analysis. | severe acute respiratory syndrome (sars) coronavirus-like viruses continue to circulate in animal reservoirs. if new mutants of sars coronavirus do initiate another epidemic, administration of prophylactic antibodies to risk groups may supplement the stringent isolation procedures that contained the first sars outbreak. | 2007 | 17298911 |
| [construction of genomic full-length cdna of sars coronavirus bj01 strain and identification of its biological characteristics]. | severe acute respiratory syndrome (sars) is an important emerging infectious disease which caused by sars coronavirus (sars-cov), and the study of its pathogenesis is needed for the treatment and prevention of this disease. to study the pathogenesis of sars-cov using reverse genetics technology, by in vitro ligation using 7 contiguous cdnas that span the entire genome of the sars-cov bj01 strain, a genomic full-length cdna was assembled, then using t7 ribomax large scale rna production systems w ... | 2006 | 17302155 |
| indomethacin has a potent antiviral activity against sars coronavirus. | severe acute respiratory syndrome (sars) is a newly emerging, highly transmissible and fatal disease caused by a previously unknown coronavirus (sars-cov). existing in non-identified animal reservoirs, sars-cov continues to represent a threat to humans because there is no effective specific antiviral therapy for coronavirus infections. | 2006 | 17302372 |
| the sars-coronavirus membrane protein induces apoptosis through modulating the akt survival pathway. | a number of viral gene products are capable of triggering apoptotic cell death through interfering with cellular signaling cascades, including the akt kinase pathway. in this study, the pro-apoptotic role of the sars-cov membrane (m) structural protein is described. we found that the sars-cov m protein induced apoptosis in both hek293t cells and transgenic drosophila. we further showed that m protein-induced apoptosis involved mitochondrial release of cytochrome c protein, and could be suppresse ... | 2007 | 17306213 |
| [a follow up study of total igm, igg, nucleoprotein and spike protein antibodies against severe acute respiratory syndrome (sars) coronavirus in patients with sars]. | to survey the dynamic changing and persistence of the special antibodies, including total igm, igg, nucleocapsid protein and spike protein antibodies, against severe acute respiratory syndrome coronavirus (sars-cov) in patients with sars. | 2006 | 17313874 |
| natural mutations in the receptor binding domain of spike glycoprotein determine the reactivity of cross-neutralization between palm civet coronavirus and severe acute respiratory syndrome coronavirus. | the severe acute respiratory syndrome (sars) outbreak of 2002 and 2003 occurred as a result of zoonotic transmission. coronavirus (cov) found in naturally infected palm civet (civet-cov) represents the closest genetic relative to sars-cov, but the degree and the determinants of cross-neutralization among these viruses remain to be investigated. studies indicate that the receptor binding domain (rbd) of the sars-cov spike (s) glycoprotein contains major determinants for viral entry and neutraliza ... | 2007 | 17314167 |