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human (non-severe acute respiratory syndrome) coronavirus infections in hospitalised children in france.this study has two objectives: to study the clinical symptoms associated with the detection of the four human coronaviruses (hcovs), 229e, oc43, nl63 and hku1 types, in the respiratory specimens sampled from hospitalised children in france between september 2004 and may 2005; and to develop a multiplex reverse transcription polymerase chain reaction (rt-pcr) assay allowing for the simultaneous detection of the four hcovs.200817999671
cloning, expression and characterization of ferret cxcl10.chemokines and their receptors function in the recruitment and activation of cells of the immune system to sites of inflammation. as such, chemokines play an important role in mediating pathophysiological events during microbial infection. in particular, cxcl9, cxcl10 and cxcl11 and their cognate receptor cxcr3 have been associated with the clinical course of several infectious diseases, including severe acute respiratory syndrome (sars) and influenza. while cxcl9, cxcl10 and cxcl11 share the sa ...200818006061
safety and immunogenicity from a phase i trial of inactivated severe acute respiratory syndrome coronavirus vaccine.emergence of severe acute respiratory syndrome (sars) from the winter of 2002 to the spring of 2003 has caused a serious threat to public health.200718018769
interaction of a peptide from the pre-transmembrane domain of the severe acute respiratory syndrome coronavirus spike protein with phospholipid membranes.the severe acute respiratory syndrome coronavirus (sars-cov) envelope spike (s) glycoprotein, a class i viral fusion protein, is responsible for the fusion between the membranes of the virus and the target cell. in order to gain new insight into the protein membrane alteration leading to the viral fusion mechanism, a peptide pertaining to the putative pre-transmembrane domain (ptm) of the s glycoprotein has been studied by infrared and fluorescence spectroscopies regarding its structure, its abi ...200718020324
sars-cov accessory protein 7a directly interacts with human lfa-1.the sars-cov accessory protein 7a is a type i membrane protein with an extracellular domain of 81 amino acid residues. it is described to be expressed during infection and to be a component of the virus particle surface. in this study, we demonstrate that protein 7a binds directly and specifically to human lymphocyte function-associated antigen 1 (lfa-1) on the cell surface of jurkat cells. the binding is increased upon artificial cell activation with phorbol ester. these observations are confir ...200718020948
coinfection of pigs with porcine respiratory coronavirus and bordetella bronchiseptica.coinfection with two or more pathogens is a common occurrence in respiratory diseases of most species. the manner in which multiple pathogens interact is not always straightforward, however. bordetella bronchiseptica and porcine respiratory coronavirus (prcv) are respiratory pathogens of pigs whose relatives, b. pertussis and the sars virus, cause respiratory disease in humans. in an initial experiment, the effect of coinfection of prcv and b. bronchiseptica was examined in thirty, 4-week-old pi ...200818022332
sars-cov replicates in primary human alveolar type ii cell cultures but not in type i-like cells.severe acute respiratory syndrome (sars) is a disease characterized by diffuse alveolar damage. we isolated human alveolar type ii cells and maintained them in a highly differentiated state. type ii cell cultures supported sars-cov replication as evidenced by rt-pcr detection of viral subgenomic rna and an increase in virus titer. virus titers were maximal by 24 h and peaked at approximately 10(5) pfu/ml. two cell types within the cultures were infected. one cell type was type ii cells, which we ...200818022664
sensitive and specific enzyme-linked immunosorbent assay using chemiluminescence for detection of severe acute respiratory syndrome viral infection.here we report the development of a more-sensitive immunoassay for severe acute respiratory syndrome (sars) based on an enzyme-linked immunosorbent assay using chemiluminescence (cleia) to detect the viral nucleocapsid (n) antigen in nasopharyngeal aspirate (npa) from patients infected with sars coronavirus (cov). the cleia was established with an optical combination of monoclonal antibodies (mabs) against sars cov n protein prepared from mice immunized with recombinant n protein without cultiva ...200818032623
are nidoviruses hijacking the autophagy machinery?autophagy is an intracellular catabolic transport route conserved among all eukaryotic cells. it has multiple important physiological functions, one of which is to act as an immune mechanism against intracellular microbes.(1,2) bacteria and viruses targeted for destruction are sequestered into large double-membrane vesicles called autophagosomes and subsequently delivered to the lysosomes where they are consumed by resident hydrolases. unfortunately, conserved cellular pathways are often exploit ...200818032917
theoretically estimated risk of severe acute respiratory syndrome transmission through blood transfusion during an epidemic in shenzhen, guangdong, china in 2003.severe acute respiratory syndrome (sars) is a newly recognized infectious disease that caused an outbreak in south china in 2003. the cause of sars was identified as a novel coronavirus (cov). the existence of asymptomatic seroconvertors and the detection of the sars-cov rna in plasma during the course of infection all suggest that sars could, as least theoretically, be transmitted by transfusion. an estimate of the risk of sars transmission through blood transfusion will contribute to decisions ...200718036985
pathology and virus dispersion in cynomolgus monkeys experimentally infected with severe acute respiratory syndrome coronavirus via different inoculation routes.severe acute respiratory syndrome-associated coronavirus (sars-cov) causes sars. the pathogenic mechanisms of sars-cov remain poorly understood. six cynomolgus monkeys were inoculated with the hku39849 isolate of sars-cov via four routes. after intranasal inoculation, the virus was isolated from respiratory swabs on days 2-7 postinoculation (p.i.) and virus genome was detected in intestinal tissues on day 7 p.i. virus was not detected after intragastric inoculation. after intravenous inoculation ...200718039277
pathology and virus dispersion in cynomolgus monkeys experimentally infected with severe acute respiratory syndrome coronavirus via different inoculation routes.severe acute respiratory syndrome-associated coronavirus (sars-cov) causes sars. the pathogenic mechanisms of sars-cov remain poorly understood. six cynomolgus monkeys were inoculated with the hku39849 isolate of sars-cov via four routes. after intranasal inoculation, the virus was isolated from respiratory swabs on days 2-7 postinoculation (p.i.) and virus genome was detected in intestinal tissues on day 7 p.i. virus was not detected after intragastric inoculation. after intravenous inoculation ...200718039277
discontinued drugs in 2006: anti-infectives.of the drugs dropped from development in 2006, 11 were being developed for infectious diseases. of these, nine were for viral diseases, including four against hiv, two against hepatitis c virus and one each against respiratory syncytial virus, severe acute respiratory syndrome (coronavirus) and a variety of viruses. the nine antiviral agents comprised six synthetic small-molecule compounds, one peptide, one monoclonal antibody and a vaccine. the remaining two agents were a vaccine for pseudomona ...200718041997
sars coronavirus accessory proteins.the emergence of the severe acute respiratory syndrome coronavirus (sars-cov) has led to a renewed interest in studying the role of accessory proteins in regulating coronavirus infections in the natural host. a significant body of evidence has accumulated in the area of sars-cov and host interactions that indicate that the accessory proteins might play an important role in modulating the host response to virus infection and thereby, contribute to pathogenesis. in this review, we have compiled th ...200818045721
structural and functional analyses of the severe acute respiratory syndrome coronavirus endoribonuclease nsp15.the severe acute respiratory syndrome (sars) coronavirus encodes several rna-processing enzymes that are unusual for rna viruses, including nsp15 (nonstructural protein 15), a hexameric endoribonuclease that preferentially cleaves 3' of uridines. we solved the structure of a catalytically inactive mutant version of nsp15, which was crystallized as a hexamer. the structure contains unreported flexibility in the active site of each subunit. substitutions in the active site residues serine 293 and ...200818045871
[optimization of expression condition of sars-cov pups genes in e. coli].according to previous studies of sars-cov (severe acute respiratory syndrome coronavirus), a variety of novel accessory genes have been identified in sars-cov genome, which were interspersed the structural genes of sars-cov and considered to be unique to the sars-cov genome. the predicted unknown proteins (pups) encoded by the accessory genes might play important roles in the sars-cov infection. three of those genes, called x4, x5 and orf10, were synthesized and introduced into e. coli to induce ...200718050746
international research networks in viral structural proteomics: again, lessons from sars.emerging and re-emerging pathogens and bioterror threats require an organized and coherent response from the worldwide research community to maximize available resources and competencies with the primary goals to understand the pathogen and enable intervention. in 2001, the structural proteomics in europe (spine) project prototyped the pan-viral structural genomic approach, and the severe acute respiratory syndrome (sars) outbreak in 2003 accelerated the concept of structural characterization of ...200818054092
severe acute respiratory syndrome-associated coronavirus nucleocapsid protein interacts with smad3 and modulates transforming growth factor-beta signaling.severe acute respiratory syndrome (sars) is an acute infectious disease with significant mortality. a typical clinical feature associated with sars is pulmonary fibrosis and the associated lung failure. however, the underlying mechanism remains elusive. in this study, we demonstrate that sars-associated coronavirus (sars-cov) nucleocapsid (n) protein potentiates transforming growth factor-beta (tgf-beta)-induced expression of plasminogen activator inhibitor-1 but attenuates smad3/smad4-mediated ...200818055455
evidence of the recombinant origin of a bat severe acute respiratory syndrome (sars)-like coronavirus and its implications on the direct ancestor of sars coronavirus.bats have been identified as the natural reservoir of severe acute respiratory syndrome (sars)-like and sars coronaviruses (slcov and scov). however, previous studies suggested that none of the currently sampled bat slcovs is the descendant of the direct ancestor of scov, based on their relatively distant phylogenetic relationship. in this study, evidence of the recombinant origin of the genome of a bat slcov is demonstrated. we identified a potential recombination breakpoint immediately after t ...200818057240
human monoclonal antibodies by immortalization of memory b cells.the administration of hyper immune sera to prevent or treat life-threatening infections is a remarkable milestone in medicine and biotechnology that has been achieved more than a century ago. yet, the therapeutic use of monoclonal antibodies in this field has developed slowly over the last decades. here we compare and contrast current methods to generate human monoclonal antibodies and highlight the advantages of exploiting the human antibody repertoire using a novel method that allows efficient ...200718063358
heterologous expression of sars-cov orf10 and x5 genes in e. coli and streptomyces lividans tk24.in previous studies a variety of novel accessory genes has been identified that were interspersed among the structural genes of the sars-cov (severe acute respiratory syndrome coronavirus) genome. the predicted unknown proteins (pups) encoded by the accessory genes, which are considered to be unique to the sars-cov genome, might play important roles in the sars-cov infection. two of these genes, called orf10 and x5, were synthesized and introduced into e. coli and streptomyces lividans tk24, res ...200718069252
calmodulin interacts with angiotensin-converting enzyme-2 (ace2) and inhibits shedding of its ectodomain.angiotensin-converting enzyme-2 (ace2) is a regulatory protein of the renin-angiotensin system (ras) and a receptor for the causative agent of severe-acute respiratory syndrome (sars), the sars-coronavirus. we have previously shown that ace2 can be shed from the cell surface in response to phorbol esters by a process involving tnf-alpha converting enzyme (tace; adam17). in this study, we demonstrate that inhibitors of calmodulin also stimulate shedding of the ace2 ectodomain, a process at least ...200818070603
intratracheal inoculation of severe acute respiratory syndrome coronavirus in monkeys macaca rhesus.an animal model for infection with severe acute respiratory syndrome coronavirus (sarscov) was evaluated in monkeys macaca rhesus. the monkeys were inoculated into the trachea with ns-i strain of sars-cov and the clinical manifestation of the illness was monitored. the clinical samples collected from infected monkeys were examined by immumnofluorescence assay (ifa), pathological inspection, rtpcr, and by virus isolation. the infected animals demonstrated mild clinical symptoms including fever. t ...200718076307
difference in receptor usage between severe acute respiratory syndrome (sars) coronavirus and sars-like coronavirus of bat origin.severe acute respiratory syndrome (sars) is caused by the sars-associated coronavirus (sars-cov), which uses angiotensin-converting enzyme 2 (ace2) as its receptor for cell entry. a group of sars-like covs (sl-covs) has been identified in horseshoe bats. sl-covs and sars-covs share identical genome organizations and high sequence identities, with the main exception of the n terminus of the spike protein (s), known to be responsible for receptor binding in covs. in this study, we investigated the ...200818077725
isolation of inhibitory rna aptamers against severe acute respiratory syndrome (sars) coronavirus ntpase/helicase.recent outbreak of severe acute respiratory syndrome (sars) that caused almost 800 victims requires a development of efficient inhibitor against sars coronavirus (scv). in this study, rna aptamers against scv ntpase/helicase (nsp10) were isolated from rna library containing random sequences of 40 nts using in vitro selection technique. nucleotide sequences of enriched rna aptamer pool (es15 rna) contain ag-rich conserved sequence of 10-11 nucleotides [aaaggr(g)gaag; r, purine base] and/or additi ...200818082623
[development and application of a safe sars-cov neutralization assay based on lentiviral vectors pseudotyped with sars-cov spike protein].the severe acute respiratory syndrome-associated coronavirus (sars-cov) spike protein (s) is a major target for neutralizing antibody. to develop and apply a safe neutralization assay for sars-cov, lentiviral sars-cov s pseudotypes had been constructed based on a three plasmid system, which contained pvrc8304 (harboring codon optimized full-length sars-cov s protein), pcmv delta 8. 2 (hiv-1 gag/pol construct) and phr'cmv egfp (the green fluorescent protein reporter construct). the pseudo-typed l ...200718092680
the spike protein of infectious bronchitis virus is retained intracellularly by a tyrosine motif.we have analyzed the intracellular transport of the spike (s) protein of infectious bronchitis virus (ibv), an avian coronavirus. surface expression was analyzed by immunofluorescence microscopy, by surface biotinylation, and by syncytium formation by s-expressing cells. by applying these methods, the s protein was found to be retained intracellularly. tyr1143 in the cytoplasmic tail was shown to be a crucial component of the retention signal. deletion of a dilysine motif that has previously bee ...200818094153
mechanisms of zoonotic severe acute respiratory syndrome coronavirus host range expansion in human airway epithelium.in 2003, severe acute respiratory syndrome coronavirus (sars-cov) emerged and caused over 8,000 human cases of infection and more than 700 deaths worldwide. zoonotic sars-cov likely evolved to infect humans by a series of transmission events between humans and animals for sale in china. using synthetic biology, we engineered the spike protein (s) from a civet strain, sz16, into our epidemic strain infectious clone, creating the chimeric virus icsz16-s, which was infectious but yielded progeny vi ...200818094188
cell type-specific cleavage of nucleocapsid protein by effector caspases during sars coronavirus infection.the epidemic outbreak of severe acute respiratory syndrome (sars) in 2003 was caused by a novel coronavirus (cov), designated sars-cov. the rna genome of sars-cov is complexed by the nucleocapsid protein (n) to form a helical nucleocapsid. besides this primary function, n seems to be involved in apoptotic scenarios. we show that upon infection of vero e6 cells with sars-cov, which elicits a pronounced cytopathic effect and a high viral titer, n is cleaved by caspases. in contrast, in sars-cov-in ...200818155731
the search for a structural basis for therapeutic intervention against the sars coronavirus.the 2003 outbreak of severe acute respiratory syndrome (sars), caused by a previously unknown coronavirus called sars-cov, had profound social and economic impacts worldwide. since then, structure-function studies of sars-cov proteins have provided a wealth of information that increases our understanding of the underlying mechanisms of sars. while no effective therapy is currently available, considerable efforts have been made to develop vaccines and drugs to prevent sars-cov infection. in this ...200818156685
preparation of armored rna as a control for multiplex real-time reverse transcription-pcr detection of influenza virus and severe acute respiratory syndrome coronavirus.the common respiratory viruses, including influenza a, influenza b, and newly emerging severe acute respiratory syndrome (sars) viruses, may cause similar clinical symptoms. therefore, differential diagnosis of these virus pathogens is frequently required for single clinical samples. in addition, there is an urgent need for noninfectious and stable rna standards and controls for multivirus detection. in this study, reverse transcription-pcr (rt-pcr) targeting of the rnas of influenza a and influ ...200818160451
comparison of effectiveness of whole viral, n and n199 proteins by elisa for the rapid diagnosis of severe acute respiratory syndrome coronavirus.although severe acute respiratory syndrome (sars) has been controlled, the subsequently emerging sporadic cases in 2004 emphasize the necessity of developing a rapid diagnostic method, which would be of great help in clinical diagnosis and also wild host screening. this study aims to establish an effective and rapid serological tool for the diagnosis of sars-cov by comparison among whole viral, n and n199 proteins by elisa.200718167201
intranasal vaccination of recombinant adeno-associated virus encoding receptor-binding domain of severe acute respiratory syndrome coronavirus (sars-cov) spike protein induces strong mucosal immune responses and provides long-term protection against sars-cov infection.we have previously reported that a subunit protein vaccine based on the receptor-binding domain (rbd) of severe acute respiratory syndrome coronavirus (sars-cov) spike protein and a recombinant adeno-associated virus (raav)-based rbd (rbd-raav) vaccine could induce highly potent neutralizing ab responses in immunized animals. in this study, systemic, mucosal, and cellular immune responses and long-term protective immunity induced by rbd-raav were further characterized in a balb/c mouse model, wi ...200818178835
residues on the dimer interface of sars coronavirus 3c-like protease: dimer stability characterization and enzyme catalytic activity analysis.3c-like protease (3cl pro) plays pivotal roles in the life cycle of severe acute respiratory syndrome coronavirus (sars-cov) and only the dimeric protease is proposed as the functional form. guided by the crystal structure and molecular dynamics simulations, we performed systematic mutation analyses to identify residues critical for 3cl pro dimerization and activity in this study. seven residues on the dimer interface were selected for evaluating their contributions to dimer stability and cataly ...200818182387
chimeric coronavirus-like particles carrying severe acute respiratory syndrome coronavirus (scov) s protein protect mice against challenge with scov.we tested the efficacy of coronavirus-like particles (vlps) for protecting mice against severe acute respiratory syndrome coronavirus (scov) infection. coexpression of scov s protein and e, m and n proteins of mouse hepatitis virus in 293t or cho cells resulted in the efficient production of chimeric vlps carrying scov s protein. balb/c mice inoculated with a mixture of chimeric vlps and alum twice at an interval of four weeks were protected from scov challenge, as indicated by the absence of in ...200818191004
determination and application of immunodominant regions of sars coronavirus spike and nucleocapsid proteins recognized by sera from different animal species.knowledge of immunodominant regions in major viral antigens is important for rational design of effective vaccines and diagnostic tests. although there have been many reports of such work done for sars-cov, these were mainly focused on the immune responses of humans and mice. in this study, we aim to search for and compare immunodominant regions of the spike (s) and nucleocapsid (n) proteins which are recognized by sera from different animal species, including mouse, rat, rabbit, civet, pig and ...200818191140
structural basis for potent cross-neutralizing human monoclonal antibody protection against lethal human and zoonotic severe acute respiratory syndrome coronavirus challenge.severe acute respiratory syndrome coronavirus (sars-cov) emerged in 2002, and detailed phylogenetic and epidemiological analyses have suggested that it originated from animals. the spike (s) glycoprotein has been identified as a major component of protective immunity, and 23 different amino acid changes were noted during the expanding epidemic. using a panel of sars-cov recombinants bearing the s glycoproteins from isolates representing the zoonotic and human early, middle, and late phases of th ...200818199635
aromatic amino acids in the juxtamembrane domain of severe acute respiratory syndrome coronavirus spike glycoprotein are important for receptor-dependent virus entry and cell-cell fusion.the severe acute respiratory syndrome coronavirus (sars-cov) spike glycoprotein (s) is a class i viral fusion protein that binds to its receptor glycoprotein, human angiotensin converting enzyme 2 (hace2), and mediates virus entry and cell-cell fusion. the juxtamembrane domain (jmd) of s is an aromatic amino acid-rich region proximal to the transmembrane domain that is highly conserved in all coronaviruses. alanine substitutions for one or two of the six aromatic residues in the jmd did not alte ...200818199653
dna hybridization biosensors using polylysine modified spces.two electrochemical dna hybridization biosensors (genosensors) for the detection of a 30-mer sequence unique to severe acute respiratory syndrome (sars) virus are described in this work. both genosensors rely on the hybridization of the oligonucleotide target with its complementary probe, which is immobilized on positively charged polylysine modified screen-printed carbon electrodes (spces), through electrostatic interactions. in one design, a biotinylated target is used and the detection of the ...200818207382
application of proteinchip array profiling in serum biomarker discovery for patients suffering from severe acute respiratory syndrome.a new strain of coronavirus has caused an outbreak of severe acute respiratory syndrome (sars) from 2002 to 2003 resulting in 774 deaths worldwide. by protein chip array profiling technology, a number of serum biomarkers that might be useful in monitoring the clinical course of sars patients were identified. this book chapter describes how the protein chip array profiling was carried out for this study. briefly, sars patients' serum samples were first fractionated in q ceramic hyperd ion exchang ...200718220240
sars coronavirus anti-infectives.severe acute respiratory syndrome (sars) emerged in late 2002 and was controlled in july 2003 by public health measures. its causative agent, sars coronavirus (sars-cov) jumped from an animal reservoir to humans and has the potential to re-emerge. following the sequencing of the genetic code and the deciphering of some of the functions of its proteins, including the cellular receptors and host proteins that participate in the life cycle of the virus, promising lead drugs and new uses of old drug ...200618221155
recent patents on treatment of severe acute respiratory syndrome (sars).severe acute respiratory syndrome (sars) is an epidemic that spread worldwide in early 2003. the aetiological agent was originally defined as a novel coronavirus and later designated as the sars coronavirus (sars-cov), which appears similar to other coronaviruses in both virion structure and genome organization with a single-stranded, plus-sense rna. however, the epidemiology and pathogenesis of sars remain poorly understood and there is currently no effective treatment. to date, considerable re ...200718221160
sars coronavirus entry into host cells through a novel clathrin- and caveolae-independent endocytic pathway.while severe acute respiratory syndrome coronavirus (sars-cov) was initially thought to enter cells through direct fusion with the plasma membrane, more recent evidence suggests that virus entry may also involve endocytosis. we have found that sars-cov enters cells via ph- and receptor-dependent endocytosis. treatment of cells with either sars-cov spike protein or spike-bearing pseudoviruses resulted in the translocation of angiotensin-converting enzyme 2 (ace2), the functional receptor of sars- ...200818227861
the sars-cov ferret model in an infection-challenge study.phase i human clinical studies involving therapeutics for emerging and biodefense pathogens with low incidence, such as the severe acute respiratory syndrome coronavirus (sars-cov), requires at a minimum preclinical evaluation of efficacy in two well-characterized and robust animal models. thus, a ferret sars-cov model was evaluated over a period of 58 days following extensive optimization and characterization of the model in order to validate clinical, histopathological, virological and immunol ...200818234270
steady-state and pre-steady-state kinetic evaluation of severe acute respiratory syndrome coronavirus (sars-cov) 3clpro cysteine protease: development of an ion-pair model for catalysis.severe acute respiratory syndrome (sars) was a worldwide epidemic caused by a coronavirus that has a cysteine protease (3clpro) essential to its life cycle. steady-state and pre-steady-state kinetic methods were used with highly active 3clpro to characterize the reaction mechanism. we show that 3clpro has mechanistic features common and disparate to the archetypical proteases papain and chymotrypsin. the kinetic mechanism for 3clpro-mediated ester hydrolysis, including the individual rate consta ...200818237196
genetic diversity-independent neutralization of pandemic viruses (e.g. hiv), potentially pandemic (e.g. h5n1 strain of influenza) and carcinogenic (e.g. hbv and hcv) viruses and possible agents of bioterrorism (variola) by enveloped virus neutralizing compounds (evncs).genetic diversity and hypermutation contribute to difficulties in developing a vaccine against viruses like hiv and influenza. there are currently no known immune correlates of protection against hiv. this has made the development of a vaccine against hiv that would provide sterilizing immunity in the near future an impossible task. the abandonment of a recent aids vaccine human trial due to a failure to elicit a protective sterilising immune response confirms that empirical attempts to develop ...200818241960
the nucleocapsid protein of sars-associated coronavirus inhibits b23 phosphorylation.severe acute respiratory syndrome-associated coronavirus (sars-cov) is responsible for sars infection. nucleocapsid (n) protein of sars-cov encapsidates the viral rna and plays an important role in virus particle assembly and release. in this study, the n protein of sars-cov was found to associate with b23, a phosphoprotein in nucleolus, in vitro and in vivo. mapping studies localized the critical n sequences for this interaction to amino acid residues 175-210, which included a serine/arginine ( ...200818243139
the sars-coronavirus plnc domain of nsp3 as a replication/transcription scaffolding protein.many genetic and mechanistic features distinguish the coronavirus replication machinery from that encoded by most other rna viruses. the coronavirus replication/transcription complex is an assembly of viral and, most probably, cellular proteins that mediate the synthesis of both the unusually large (approximately 30 kb) rna genome and an extensive set of subgenomic mrnas. the viral components of the complex are encoded by the giant replicase gene, which is expressed in the form of two polyprotei ...200818255185
[sars corona virus--a new dilemma].in late 2002, cases of life-threatening respiratory disease with no identifiable cause were reported from guangdong province, china, and they were followed by reports from other countries. the syndrome was designated "severe acute respiratory syndrome" (sars). investigators used a combination of traditional methods and molecular techniques to identitify the unknown pathogen. researches showed that sars is caused by a new coronavirus, never detected before and which is not related to any of the k ...200518257204
duration of antibody responses after severe acute respiratory syndrome.among 176 patients who had had severe acute respiratory syndrome (sars), sars-specific antibodies were maintained for an average of 2 years, and significant reduction of immunoglobulin g-positive percentage and titers occurred in the third year. thus, sars patients might be susceptible to reinfection >or=3 years after initial exposure.200718258008
sequential affinity purification of peroxidase tagged bispecific anti-sars-cov antibodies on phenylboronic acid agarose.hybrid hybridomas (quadromas) are derived by fusing at least two hybridomas, each producing a different antibody of predefined specificity. the resulting cell secretes not only the immunoglobulins of both parents but also hybrid molecules manifesting the binding characteristics of the individual fusion partners. purification of the desired bispecific immunoprobe with high specific activity from a mixture of bispecific and monospecific monoclonal antibodies requires special strategies. using a du ...200818258500
correlation between dissociation and catalysis of sars-cov main protease.the dimeric interface of severe acute respiratory syndrome coronavirus main protease is a potential target for the anti-sars drug development. we have generated c-terminal truncated mutants by serial truncations. the quaternary structure of the enzyme was analyzed using both sedimentation velocity and sedimentation equilibrium analytical ultracentrifugation. global analysis of the combined results showed that truncation of c-terminus from 306 to 300 had no appreciable effect on the quaternary st ...200818275836
lipid rafts are involved in sars-cov entry into vero e6 cells.lipid rafts often serve as an entry site for certain viruses. here, we report that lipid rafts in vero e6 cells are involved in the entry of severe acute respiratory syndrome coronavirus (sars-cov). infectivity assay showed the integrity of lipid rafts was required for productive infection of pseudotyped sars-cov. depletion of plasma membrane cholesterol with mbetacd relocalized raft-resident marker caveolin-1 as well as sars-cov receptor ace2 to a nonraft environment, but did not significantly ...200818279660
priming with raav encoding rbd of sars-cov s protein and boosting with rbd-specific peptides for t cell epitopes elevated humoral and cellular immune responses against sars-cov infection.development of vaccines against severe acute respiratory syndrome (sars) coronavirus (sars-cov) is crucial in the prevention of sars reemergence. the receptor-binding domain (rbd) of sars-cov spike (s) protein is an important target in developing safe and effective sars vaccines. our previous study has demonstrated that vaccination with adeno-associated virus encoding rbd (rbd-raav) induces high titer of neutralizing antibodies. in this study, we further assessed the immune responses and protect ...200818289745
aryl methylene ketones and fluorinated methylene ketones as reversible inhibitors for severe acute respiratory syndrome (sars) 3c-like proteinase.the severe acute respiratory syndrome (sars) virus depends on a chymotrypsin-like cysteine proteinase (3cl(pro)) to process the translated polyproteins to functional viral proteins. this enzyme is a target for the design of potential anti-sars drugs. a series of ketones and corresponding mono- and di-fluoro ketones having two or three aromatic rings were synthesized as possible reversible inhibitors of sars 3cl(pro). the design was based on previously established potent inhibition of the enzyme ...200818295820
development of subunit vaccines against severe acute respiratory syndrome.severe acute respiratory syndrome (sars) is a novel infectious disease caused by sars coronavirus (sars-cov). although sars appears to have been successfully contained, there is still a risk for its reemergence due to sporadic laboratory accidents or the presence of a natural reservoir for sars-cov-like virus. therefore, the development of effective vaccines against sars-cov continues to be the current focus of sars research. this review will first describe the rationale for developing safe and ...200818301805
mechanism for controlling the dimer-monomer switch and coupling dimerization to catalysis of the severe acute respiratory syndrome coronavirus 3c-like protease.unlike 3c protease, the severe acute respiratory syndrome coronavirus (sars-cov) 3c-like protease (3clpro) is only enzymatically active as a homodimer and its catalysis is under extensive regulation by the unique extra domain. despite intense studies, two puzzles still remain: (i) how the dimer-monomer switch is controlled and (ii) why dimerization is absolutely required for catalysis. here we report the monomeric crystal structure of the sars-cov 3clpro mutant r298a at a resolution of 1.75 a. d ...200818305031
without its n-finger, the main protease of severe acute respiratory syndrome coronavirus can form a novel dimer through its c-terminal domain.the main protease (m(pro)) of severe acute respiratory syndrome coronavirus (sars-cov) plays an essential role in the extensive proteolytic processing of the viral polyproteins (pp1a and pp1ab), and it is an important target for anti-sars drug development. it was found that sars-cov m(pro) exists in solution as an equilibrium of both monomeric and dimeric forms, and the dimeric form is the enzymatically active form. however, the mechanism of sars-cov m(pro) dimerization, especially the roles of ...200818305043
severe acute respiratory syndrome coronavirus nsp1 suppresses host gene expression, including that of type i interferon, in infected cells.the severe acute respiratory syndrome coronavirus (sars-cov) nsp1 protein has unique biological functions that have not been described in the viral proteins of any rna viruses; expressed sars-cov nsp1 protein has been found to suppress host gene expression by promoting host mrna degradation and inhibiting translation. we generated an nsp1 mutant (nsp1-mt) that neither promoted host mrna degradation nor suppressed host protein synthesis in expressing cells. both a sars-cov mutant virus, encoding ...200818305050
rnase-resistant virus-like particles containing long chimeric rna sequences produced by two-plasmid coexpression system.rnase-resistant, noninfectious virus-like particles containing exogenous rna sequences (armored rna) are good candidates as rna controls and standards in rna virus detection. however, the length of rna packaged in the virus-like particles with high efficiency is usually less than 500 bases. in this study, we describe a method for producing armored l-rna. armored l-rna is a complex of ms2 bacteriophage coat protein and rna produced in escherichia coli by the induction of a two-plasmid coexpressio ...200818305135
roles of tnf-alpha gene polymorphisms in the occurrence and progress of sars-cov infection: a case-control study.host genetic factors may play a role in the occurrence and progress of sars-cov infection. this study was to investigate the relationship between tumor necrosis factor (tnf)-alpha gene polymorphisms with the occurrence of sars-cov infection and its role in prognosis of patients with lung interstitial fibrosis and femoral head osteonecrosis.200818312678
thiopurine analogues inhibit papain-like protease of severe acute respiratory syndrome coronavirus.the papain-like protease of severe acute respiratory syndrome coronavirus (plpro) (ec 3.4.22.46) is essential for the viral life cycle and therefore represents an important antiviral target. we have identified 6mp and 6tg as reversible and slow-binding inhibitors of sars-cov plpro, which is the first report about small molecule reversible inhibitors of plpro. the inhibition mechanism was investigated by kinetic measurements and computer docking. both compounds are competitive, selective, and rev ...200818313035
thrombopoietin levels increased in patients with severe acute respiratory syndrome.hematological changes in patients with severe acute respiratory syndrome (sars) are common and frequently include thrombocytopenia. using a elisa method, we found an increase in thrombopoietin (tpo) levels in the plasma of convalesced sars patients (290+/-53 pg/ml) and active sars patients (251+/-23 pg/ml) comparing to that from normal control patients (228+/-17 pg/ml). in addition, the plasma from active sars patients had an inhibitory effect on cfu-mk formation, which could be neutralized by a ...200818314161
amiodarone alters late endosomes and inhibits sars coronavirus infection at a post-endosomal level.amiodarone interferes with the endocytic pathway, inhibits proteolysis, and causes the formation of vacuoles, but uptake and intracellular distribution of the drug, origin of vacuoles, and functional consequences of amiodarone accumulation remain unclear. our objective was to study amiodarone uptake, clarify the origin of vacuoles, and investigate the effect of amiodarone on the life cycle of the coronavirus responsible for the severe acute respiratory syndrome (sars), which, to enter cells, rel ...200818314540
peptide mimicrying between sars coronavirus spike protein and human proteins reacts with sars patient serum.molecular mimicry, defined as similar structures shared by molecules from dissimilar genes or proteins, is a general strategy used by pathogens to infect host cells. severe acute respiratory syndrome (sars) is a new human respiratory infectious disease caused by sars coronavirus (sars-cov). the spike (s) protein of sars-cov plays an important role in the virus entry into a cell. in this study, eleven synthetic peptides from the s protein were selected based on its sequence homology with human pr ...200818320019
interferon and cytokine responses to sars-coronavirus infection.the sudden emergence of severe acute respiratory syndrome (sars) has boosted research on innate immune responses to coronaviruses. it is now well established that the causative agent, a newly identified coronavirus termed sars-cov, employs multiple passive and active mechanisms to avoid induction of the antiviral type i interferons in tissue cells. by contrast, chemokines such as ip-10 or il-8 are strongly upregulated. the imbalance in the ifn response is thought to contribute to the establishme ...200818321765
design, synthesis, and evaluation of trifluoromethyl ketones as inhibitors of sars-cov 3cl protease.a series of trifluoromethyl ketones as sars-cov 3cl protease inhibitors was developed. the inhibitors were synthesized in four steps from commercially available compounds. three different amino acids were explored in the p1-position and in the p2-p4 positions varying amino acids and long alkyl chain were incorporated. all inhibitors were evaluated in an in vitro assay using purified enzyme and fluorogenic substrate peptide. one of the inhibitors showed a time-dependent inhibition, with a k(i) va ...200818329272
[lessons from sars: a new potential therapy for acute respiratory distress syndrome (ards) with angiotensin converting enzyme 2 (ace2)].during several months of 2002, severe acute respiratory syndrome (sars) caused by sars-coronavirus (sars-cov) spread rapidly from china throughout the world causing more than 800 deaths due to the development of acute respiratory distress syndrome (ards). interestingly, a novel homologue of angiotensin converting-enzyme (ace), termed angiotensin converting enzyme 2 (ace2) has been identified as a receptor for sars-cov. ace and ace2 share homology in their catalytic domain and provide different k ...200818340998
structure-based virtual screening against sars-3cl(pro) to identify novel non-peptidic hits.severe acute respiratory syndrome is a highly infectious upper respiratory tract disease caused by sars-cov, a previously unidentified human coronavirus. sars-3cl(pro) is a viral cysteine protease critical to the pathogen's life cycle and hence a therapeutic target of importance. the recently elucidated crystal structures of this enzyme provide an opportunity for the discovery of inhibitors through rational drug design. in the current study, gold docking program was utilized to conduct extensive ...200818343121
pathological changes in masked palm civets experimentally infected by severe acute respiratory syndrome (sars) coronavirus.masked palm civets are highly susceptible to infection with the severe acute respiratory syndrome coronavirus (sars-cov). infected animals become less aggressive and develop pyrexia, lethargy and diarrhoea. the present study describes the spectrum of histopathological changes in the lung, spleen, lymph node, liver, small intestine, kidney and cerebrum of civets infected experimentally with sars-cov. in-situ hybridization (ish) with probes specific for the rna polymerase gene demonstrated viral r ...200818343398
pathological changes in masked palm civets experimentally infected by severe acute respiratory syndrome (sars) coronavirus.masked palm civets are highly susceptible to infection with the severe acute respiratory syndrome coronavirus (sars-cov). infected animals become less aggressive and develop pyrexia, lethargy and diarrhoea. the present study describes the spectrum of histopathological changes in the lung, spleen, lymph node, liver, small intestine, kidney and cerebrum of civets infected experimentally with sars-cov. in-situ hybridization (ish) with probes specific for the rna polymerase gene demonstrated viral r ...200818343398
identification of residues in the receptor-binding domain (rbd) of the spike protein of human coronavirus nl63 that are critical for the rbd-ace2 receptor interaction.human coronavirus nl63 (nl63), a member of the group i coronaviruses, may cause acute respiratory diseases in young children and immunocompromised adults. like severe acute respiratory syndrome coronavirus (sars-cov), nl63 also employs the human angiotensin-converting enzyme 2 (hace2) receptor for cellular entry. to identify residues in the spike protein of nl63 that are important for hace2 binding, this study first generated a series of s1-truncated variants, examined their associations with th ...200818343844
induction of neutralising antibodies and cellular immune responses against sars coronavirus by recombinant measles viruses.live attenuated recombinant measles viruses (rmv) expressing a codon-optimised spike glycoprotein (s) or nucleocapsid protein (n) of severe acute respiratory syndrome-associated coronavirus (sars-cov) were generated (rmv-s and rmv-n). both recombinant viruses stably expressed the corresponding sars-cov proteins, grew to similar end titres as the parental strain and induced high antibody titres against mv and the vectored sars-cov antigens (s and n) in transgenic mice susceptible to measles infec ...200818346823
identification of a novel coronavirus from a beluga whale by using a panviral microarray.the emergence of viruses such as severe acute respiratory syndrome coronavirus and nipah virus has underscored the role of animal reservoirs in human disease and the need for reservoir surveillance. here, we used a panviral dna microarray to investigate the death of a captive beluga whale in an aquatic park. a highly divergent coronavirus, tentatively named coronavirus sw1, was identified in liver tissue from the deceased whale. subsequently, the entire genome of sw1 was sequenced, yielding a ge ...200818353961
effects of different immunization protocols and adjuvant on antibody responses to inactivated sars-cov vaccine.severe acute respiratory syndrome (sars) is a deadly and highly infectious disease caused by sars coronavirus (sars-cov). inactivated sars-cov has been explored as a vaccine against sars-cov; however, current knowledge of inactivated sars-cov vaccine is quite limited. we attempted to investigate the effects of different immunization protocols and adjuvant on the antibody responses to inactivated sars-cov vaccine. with an intraperitoneal (ip) immunization protocol, inactivated sars-cov alone indu ...200818355120
phytochemical analysis and in vitro antiviral activities of the essential oils of seven lebanon species.the chemical composition of the essential oils of laurus nobilis, juniperus oxycedrus ssp. oxycedrus, thuja orientalis, cupressus sempervirens ssp. pyramidalis, pistacia palaestina, salvia officinalis, and satureja thymbra was determined by gc/ms analysis. essential oils have been evaluated for their inhibitory activity against sars-cov and hsv-1 replication in vitro by visually scoring of the virus-induced cytopathogenic effect post-infection. l. nobilis oil exerted an interesting activity agai ...200818357554
[detection of the mrna expression of human angiotensin-converting enzyme 2 as a sars coronavirus functional receptor in human femoral head].to investigate the mrna expression of severe acute respiratory syndrome-associated coronavirus (sars-cov) functional receptor, angiotensin-converting enzyme 2 (ace2), in human femoral head and conjunctiva, and explore the possible entry route of sars-cov in human femoral head.200818359708
reduced incorporation of sars-cov spike protein into viral particles due to amino acid substitutions within the receptor binding domain.cell clone #21 is a long-term producer of the infectious sars-coronavirus, although the incorporation rate of spike (s) protein into virions is significantly lower. sequencing analysis of the viral structural proteins revealed four and one amino acid substitutions in the s and membrane (m) proteins, respectively. we demonstrated, using a viral-like particle formation system, that the s mutations were involved in the lower incorporation of the s protein into virions, although the m mutation that ...200818362400
proteomics analysis unravels the functional repertoire of coronavirus nonstructural protein 3.severe acute respiratory syndrome (sars) coronavirus infection and growth are dependent on initiating signaling and enzyme actions upon viral entry into the host cell. proteins packaged during virus assembly may subsequently form the first line of attack and host manipulation upon infection. a complete characterization of virion components is therefore important to understanding the dynamics of early stages of infection. mass spectrometry and kinase profiling techniques identified nearly 200 inc ...200818367524
persistent replication of severe acute respiratory syndrome coronavirus in human tubular kidney cells selects for adaptive mutations in the membrane protein.severe acute respiratory syndrome (sars) is a systemic disease characterized by both lung pathology and widespread extrapulmonary virus dissemination causing multiple organ injuries. in this regard, renal dysfunction is an ominous sign in patients with sars. indeed, clusters of sars coronavirus (sars-cov) particles have been detected in the cytoplasm of renal tubular epithelial cells in postmortem studies, explaining the presence of infectious virus in the urine of sars patients. in order to inv ...200818367528
application of sirna against sars in the rhesus macaque model.containment of the sars coronavirus (scv) outbreak was accompanied by the rapid characterization of this new pathogen's genome sequence in 2003, encouraging the development of anti-scv therapeutics using short interfering rna (sirna) inhibitors. a pair of sirna duplexes identified as potent scv inhibitors in vitro was evaluated for in vivo efficacy and safety in a rhesus macaque sars model using intranasal administration with clinical viable delivery carrier in three dosing regimens. observation ...200818369784
application of sirna against sars in the rhesus macaque model.containment of the sars coronavirus (scv) outbreak was accompanied by the rapid characterization of this new pathogen's genome sequence in 2003, encouraging the development of anti-scv therapeutics using short interfering rna (sirna) inhibitors. a pair of sirna duplexes identified as potent scv inhibitors in vitro was evaluated for in vivo efficacy and safety in a rhesus macaque sars model using intranasal administration with clinical viable delivery carrier in three dosing regimens. observation ...200818369784
the discovery of ace2 and its role in acute lung injury.during several months of 2002, severe acute respiratory syndrome (sars) caused by sars-coronavirus (sars-cov) spread rapidly from china throughout the world causing more than 800 deaths due to the development of acute respiratory distress syndrome (ards), which is the severe form of acute lung injury (ali). interestingly, a novel homologue of angiotensin converting-enzyme (ace), termed angiotensin converting enzyme 2 (ace2) has been identified as a receptor for sars-cov. ace and ace2 share homol ...200818376004
characterization and epitope mapping of monoclonal antibodies to the nucleocapsid protein of severe acute respiratory syndrome coronavirus.the sudden emergence of severe acute respiratory syndrome (sars) at the end of 2002 resulted in 774 reported deaths from more than 8000 cases worldwide. as no effective vaccines or antiviral agents are available, the most effective measure to prevent the expansion of a sars epidemic is the rapid diagnosis and isolation of sars patients. to establish specific diagnostic methods, we generated nine clones of monoclonal antibodies to nucleocapsid protein (np) of sars-coronavirus (sars-cov). on immun ...200818380153
co-infection of respiratory bacterium with severe acute respiratory syndrome coronavirus induces an exacerbated pneumonia in mice.sars-cov grows in a variety of tissues that express its receptor, although the mechanism for high replication in the lungs and severe respiratory illness is not well understood. we recently showed that elastase enhances sars-cov infection in cultured cells, which suggests that sars development may be due to elastase-mediated, enhanced sars-cov infection in the lungs. to explore this possibility, we examined whether co-infection of mice with sars-cov and pp, a low-pathogenic bacterium which elici ...200818380809
an outbreak of human coronavirus oc43 infection and serological cross-reactivity with sars coronavirus.in summer 2003, a respiratory outbreak was investigated in british columbia, during which nucleic acid tests and serology unexpectedly indicated reactivity for severe acute respiratory syndrome coronavirus (sars-cov).200618382647
design, synthesis and screening of antisense peptide based combinatorial peptide libraries towards an aromatic region of sars-cov.a combination of high-performance affinity chromatography and antisense peptide based combinatorial peptide libraries was used to screen a potential inhibitor for sars-cov. an aromatic-amino acid-rich region within the transmembrane domain at the c terminal of spike (s) protein identified as a membrane-active region was chosen as the target sense peptide (sp) and immobilized as affinity ligand. four antisense peptides were designed based on the degeneracy of genetic codes. one of them was screen ...200818383098
sars vaccine based on a replication-defective recombinant vesicular stomatitis virus is more potent than one based on a replication-competent vector.a sars vaccine based on a live-attenuated vesicular stomatitis virus (vsv) recombinant expressing the sars-cov s protein provides long-term protection of immunized mice from sars-cov infection (kapadia, s.u., rose, j. k., lamirande, e., vogel, l., subbarao, k., roberts, a., 2005. long-term protection from sars coronavirus infection conferred by a single immunization with an attenuated vsv-based vaccine. virology 340(2), 174-82.). because it is difficult to obtain regulatory approval of vaccine b ...200818396306
interferon alfacon 1 inhibits sars-cov infection in human bronchial epithelial calu-3 cells.the primary targets for sars-cov infection are the epithelial cells in the respiratory and intestinal tract. the angiotensin-converting enzyme 2 (ace-2) has been identified as a functional receptor for sars-cov. ace-2 has been shown to be expressed at the apical domain of polarized calu-3 cells. in this report, interferon alfacon 1 was examined for inhibitory activities against sars-cov on human lung carcinoma epithelial calu-3 cell line and the other three african green monkey kidney epithelial ...200818406349
heteroaromatic ester inhibitors of hepatitis a virus 3c proteinase: evaluation of mode of action.the related 3c and 3c-like proteinase (3c(pro) and 3cl(pro)) of picornaviruses and coronaviruses, respectively, are good drug targets. as part of an effort to generate broad-spectrum inhibitors of these enzymes, we screened a library of inhibitors based on a halopyridinyl ester from a previous study of the severe acute respiratory syndrome (sars) 3cl proteinase against hepatitis a virus (hav) 3c(pro). three of the compounds, which also had furan rings, inhibited the cleavage activity of hav 3c(p ...200818407505
coronavirus nonstructural protein 16 is a cap-0 binding enzyme possessing (nucleoside-2'o)-methyltransferase activity.the coronavirus family of positive-strand rna viruses includes important pathogens of livestock, companion animals, and humans, including the severe acute respiratory syndrome coronavirus that was responsible for a worldwide outbreak in 2003. the unusually complex coronavirus replicase/transcriptase is comprised of 15 or 16 virus-specific subunits that are autoproteolytically derived from two large polyproteins. in line with bioinformatics predictions, we now show that feline coronavirus (fcov) ...200818417574
genomic characterizations of bat coronaviruses (1a, 1b and hku8) and evidence for co-infections in miniopterus bats.we previously reported the detection of bat coronaviruses (bat covs 1a, 1b, hku7, hku8 and bat-severe acute respiratory syndrome coronavirus) in miniopterus spp. that cohabit a cave in hong kong. here, we report the full genomic sequences of bat covs 1a, 1b and hku8. bat covs 1a and 1b, which are commonly found in the miniopterus, are phylogenetically closely related. using species-specific rt-pcr assays, bat covs 1a and 1b were confirmed to have distinct host specificities to miniopterus magnat ...200818420807
genomic characterizations of bat coronaviruses (1a, 1b and hku8) and evidence for co-infections in miniopterus bats.we previously reported the detection of bat coronaviruses (bat covs 1a, 1b, hku7, hku8 and bat-severe acute respiratory syndrome coronavirus) in miniopterus spp. that cohabit a cave in hong kong. here, we report the full genomic sequences of bat covs 1a, 1b and hku8. bat covs 1a and 1b, which are commonly found in the miniopterus, are phylogenetically closely related. using species-specific rt-pcr assays, bat covs 1a and 1b were confirmed to have distinct host specificities to miniopterus magnat ...200818420807
a triffic perspective on acute lung injury.acute lung injury (ali) is a leading cause of death in people infected with h5n1 avian influenza virus or the sars-coronavirus. imai et al. (2008) now report that ali is triggered by the signaling of oxidized phospholipids through toll-like receptor 4 (tlr4) and the adaptor protein trif. these findings provide insight into the molecular pathogenesis of ali, a condition for which treatment options are currently very limited.200818423191
is the anti-psychotic, 10-(3-(dimethylamino)propyl)phenothiazine (promazine), a potential drug with which to treat sars infections? lack of efficacy of promazine on sars-cov replication in a mouse model.phenothiazine and derivatives were tested for inhibition of sars-cov replication. phenothiazine slightly inhibited sars-cov replication in a neutral red (nr) uptake assay. adding a propylamino group to give promazine reduced virus yields (vyr assay) with an ec(90)=8.3+/-2.8 microm, but without selectivity. various substitutions in the basic phenothiazine structure did not promote efficacy. phenazine ethosulfate was the most potent compound by vyr assay (ec(90)=6.1+/-4.3 microm). all compounds we ...200818423639
importance of sars-cov spike protein trp-rich region in viral infectivity.sars-cov entry is mediated by spike glycoprotein. during the viral and host cellular membrane fusion, hr1 and hr2 form 6-helix bundle, positioning the fusion peptide closely to the c-terminal region of ectodomain to drive apposition and subsequent membrane fusion. connecting to the hr2 region is a trp-rich region which is absolutely conserved in members of coronaviruses. to investigate the importance of trp-rich region in sars-cov entry, we produced different mutated s proteins using alanine sca ...200818424264
clinical features, pathogenesis and immunobiology of severe acute respiratory syndrome.severe acute respiratory syndrome coronavirus is a novel virus responsible for the major pandemic in 2003, and it re-emerged in china in late 2003 and 2004 following resumption of wild animal trading activities. over the past few years, research work has looked into factors that may lead to super-spreading events, clinical/laboratory parameters that may differentiate severe acute respiratory syndrome from other causes of community-acquired pneumonia, the origin of severe acute respiratory syndro ...200818427248
identification of a novel transcriptional repressor (hepis) that interacts with nsp-10 of sars coronavirus.a novel gene was previously isolated from a cdna library of human embryo lung tissue by its encoded protein, which interacts with non-structural protein 10 (nsp-10) of the severe acute respiratory syndrome coronavirus (sars-cov). the protein was named human embryo lung cellular protein interacting with sars-cov nsp-10 (hepis), and it is composed of 147 amino acids with several ck ii phosphorylation sites. in the present study, we demonstrated that hepis was capable of suppressing chloramphenicol ...200818433331
search for potential target site of nucleocapsid gene for the design of an epitope-based sars dna vaccine.it is believed today that nucleocapsid protein (n) of severe acute respiratory syndrome (sars)-cov is one of the most promising antigen candidates for vaccine design. in this study, three fragments [n1 (residues: 1-422); n2 (residues: 1-109); n3 (residues: 110-422)] of n protein of sars-cov were expressed in escherichia coli and analyzed by pooled sera of convalescence phase of sars patients. three gene fragments [n1 (1-1269 nt), n2 (1-327 nt) and n3 (328-1269 nt)-expressing the same proteins of ...200818440652
fusion core structure of the severe acute respiratory syndrome coronavirus (sars-cov): in search of potent sars-cov entry inhibitors.severe acute respiratory coronavirus (sars-cov) spike (s) glycoprotein fusion core consists of a six-helix bundle with the three c-terminal heptad repeat (hr2) helices packed against a central coiled-coil of the other three n-terminal heptad repeat (hr1) helices. each of the three peripheral hr2 helices shows prominent contacts with the hydrophobic surface of the central hr1 coiled-coil. the concerted protein-protein interactions among the hr helices are responsible for the fusion event that lea ...200818442051
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