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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
a live attenuated severe acute respiratory syndrome coronavirus is immunogenic and efficacious in golden syrian hamsters.the immunogenicity and protective efficacy of a live attenuated vaccine consisting of a recombinant severe acute respiratory syndrome (sars) coronavirus lacking the e gene (rsars-cov-deltae) were studied using hamsters. hamsters immunized with rsars-cov-deltae developed high serum-neutralizing antibody titers and were protected from replication of homologous (sars-cov urbani) and heterologous (gd03) sars-cov in the upper and lower respiratory tract. rsars-cov-deltae-immunized hamsters remained a ...200818463152
a live attenuated severe acute respiratory syndrome coronavirus is immunogenic and efficacious in golden syrian hamsters.the immunogenicity and protective efficacy of a live attenuated vaccine consisting of a recombinant severe acute respiratory syndrome (sars) coronavirus lacking the e gene (rsars-cov-deltae) were studied using hamsters. hamsters immunized with rsars-cov-deltae developed high serum-neutralizing antibody titers and were protected from replication of homologous (sars-cov urbani) and heterologous (gd03) sars-cov in the upper and lower respiratory tract. rsars-cov-deltae-immunized hamsters remained a ...200818463152
a novel strategy for analyzing rna-protein interactions by surface plasmon resonance biosensor.surface plasmon resonance (spr) biosensor is a promising technology for its various advantages including the real-time measurement of biomolecular interactions without labeling. a method of hybridizing rnas on the surface of the streptavidin-coated (sa) sensor chip to study rna-protein interactions was described in this paper. in our study, it has been shown that the nucleocapsid (n) protein of severe acute respiratory syndrome coronavirus (sars-cov) has a high binding affinity for the leader se ...200818465270
human line1 endonuclease domain as a putative target of sars-associated autoantibodies involved in the pathogenesis of severe acute respiratory syndrome.severe acute respiratory syndrome (sars) is a disease with a mortality of 9.56%. although sars is etiologically linked to a new coronavirus (sars-cov) and functional cell receptor has been identified, the pathogenesis of the virus infection is largely unclear.200818466680
mouse-passaged severe acute respiratory syndrome-associated coronavirus leads to lethal pulmonary edema and diffuse alveolar damage in adult but not young mice.advanced age is a risk factor of severe acute respiratory syndrome (sars) in humans. to understand its pathogenesis, we developed an animal model using balb/c mice and the mouse-passaged frankfurt 1 isolate of sars coronavirus (sars-cov). we examined the immune responses to sars-cov in both young and adult mice. sars-cov induced severe respiratory illness in all adult, but not young, mice on day 2 after inoculation with a mortality rate of 30 to 50%. moribund adult mice showed severe pulmonary e ...200818467696
combination of functionalized nanoparticles and polymerase chain reaction-based method for sars-cov gene detection.rapid and sensitive detection of sars associated coronavirus is critical for early diagnosis and control of severe acute respiratory syndrome. this study describes a method for the detection of sars associated coronavirus gene by the combination of functionalized nanoparticles and pcr-based assay. in this method, the target cdna of sars associated coronavirus was firstly captured and enriched from the mixture of target cdna and non-target cdna by the use of the functionalized silica coated super ...200818468073
[emerging viral infections in belgium and abroad].viral diseases are a moving world with epidemic upsurges, the disappearance of some infections and the temporary or definitive appearance of others. each year our country is stricken by flu epidemics, but at some points of time unexpected new flu viruses may cause a worldwide pandemic. presently a number of viral diseases have disappeared or are disappearing from our country, as smallpox, poliomyelitis, rabies, measles or rubella. many factors, some changing others more persistent, may explain t ...200818479078
immunomodulatory and anti-sars activities of houttuynia cordata.severe acute respiratory syndrome (sars) is a life-threatening form of pneumonia caused by sars coronavirus (sars-cov). from late 2002 to mid 2003, it infected more than 8000 people worldwide, of which a majority of cases were found in china. owing to the absence of definitive therapeutic western medicines, houttuynia cordata thunb. (saururaceae)(hc) was shortlisted by chinese scientists to tackle sars problem as it is conventionally used to treat pneumonia.200818479853
rapid discovery and optimization of therapeutic antibodies against emerging infectious diseases.using a comprehensive set of discovery and optimization tools, antibodies were produced with the ability to neutralize sars coronavirus (sars-cov) infection in vero e6 cells and in animal models. these anti-sars antibodies were discovered using a novel dna display method, which can identify new antibodies within days. once neutralizing antibodies were identified, a comprehensive and effective means of converting the mouse sequences to human frameworks was accomplished using hufr (human framework ...200818480090
structural and dynamic characterization of the interaction of the putative fusion peptide of the s2 sars-cov virus protein with lipid membranes.the sars 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 the present work, we report a study of the binding and interaction with model membranes of a peptide pertaining to the putative fusion domain of sars-cov, sars fp, as well as the structural changes that take place in both the phospholipid and the peptide molecules upon this interaction. from fluorescence and infr ...200818489147
modulation of tnf-alpha-converting enzyme by the spike protein of sars-cov and ace2 induces tnf-alpha production and facilitates viral entry.severe acute respiratory syndrome coronavirus (sars-cov) is a high-risk infectious pathogen. in the proposed model of respiratory failure, sars-cov down-regulates its receptor, angiotensin-converting enzyme 2 (ace2), but the mechanism involved is unknown. we found that the spike protein of sars-cov (sars-s) induced tnf-alpha-converting enzyme (tace)-dependent shedding of the ace2 ectodomain. the modulation of tace activity by sars-s depended on the cytoplasmic domain of ace2, because deletion mu ...200818490652
severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ace2.infection of humans with the severe acute respiratory syndrome coronavirus (sars-cov) results in substantial morbidity and mortality, with death resulting primarily from respiratory failure. while the lungs are the major site of infection, the brain is also infected in some patients. brain infection may result in long-term neurological sequelae, but little is known about the pathogenesis of sars-cov in this organ. we previously showed that the brain was a major target organ for infection in mice ...200818495771
predicting linear b-cell epitopes using string kernels.the identification and characterization of b-cell epitopes play an important role in vaccine design, immunodiagnostic tests, and antibody production. therefore, computational tools for reliably predicting linear b-cell epitopes are highly desirable. we evaluated support vector machine (svm) classifiers trained utilizing five different kernel methods using fivefold cross-validation on a homology-reduced data set of 701 linear b-cell epitopes, extracted from bcipep database, and 701 non-epitopes, ...200818496882
coronavirus antibodies in bat biologists. 200818507931
the role of programmed-1 ribosomal frameshifting in coronavirus propagation.coronaviruses have the potential to cause significant economic, agricultural and health problems. the severe acute respiratory syndrome (sars) associated coronavirus outbreak in late 2002, early 2003 called attention to the potential damage that coronaviruses could cause in the human population. the ensuing research has enlightened many to the molecular biology of coronaviruses. a programmed -1 ribosomal frameshift is required by coronaviruses for the production of the rna dependent rna polymera ...200818508552
[sars-cov infection and pregnancy].sars is a highly contagious infection, caused by new coronavirus sars-cov. immunopathological mechanisms responsible for the reaction to sars-cov infection have not yet been fully elucidated. cytokine profile of sars patients showed marked elevation of th1 cytokine, interferon gamma, inflammatory cytokines for at least 2 weeks after the onset of the disease. the clinical manifestation of sars in patients has been of varied nature. fever of more then 38 degrees c, lasting more then 24 hours, is t ...200818510050
a chimeric multi-epitope dna vaccine elicited specific antibody response against severe acute respiratory syndrome-associated coronavirus which attenuated the virulence of sars-cov in vitro.epitope-based vaccines designed to induce antibody responses specific for severe acute respiratory syndrome-associated coronavirus (sars-cov) are being developed as a means for increasing vaccine potency. in this study, we identified four b cell epitopes from the spike (s) and membrane (m) protein through bioinformatics analysis and constructed a multi-epitope dna vaccine. intramuscular immunization of mice with this vaccine was sufficient to induce specific prime as well as a long-term memory h ...200818533276
structure of a sars coronavirus-derived peptide bound to the human major histocompatibility complex class i molecule hla-b*1501.the human leukocyte antigen (hla) class i system comprises a highly polymorphic set of molecules that specifically bind and present peptides to cytotoxic t cells. hla-b*1501 is a prototypical member of the hla-b62 supertype and only two peptide-hla-b*1501 structures have been determined. here, the crystal structure of hla-b*1501 in complex with a sars coronavirus-derived nonapeptide (vqqessfvm) has been determined at high resolution (1.87 a). the peptide is deeply anchored in the b and f pockets ...200818540051
characterization of the prefusion and transition states of severe acute respiratory syndrome coronavirus s2-hr2.the envelope glycoproteins of the class i family, which include human immunodeficiency virus (hiv), influenza, and severe acute respiratory syndrome coronavirus (sars-cov), mediate viral entry by first binding to their cellular receptors and subsequently inducing fusion of the viral and cellular membranes. in the case of sars-cov, heptad repeat domains of the envelope glycoprotein, termed s2-hr1 and s2-hr2, are thought to undergo structural changes from a prefusion state, in which s2-hr1 and s2- ...200818540634
endocytosis of the receptor-binding domain of sars-cov spike protein together with virus receptor ace2.cell entry of severe acute respiratory syndrome coronavirus (sars-cov) is mediated by the viral spike (s) protein. amino acids 319-510 on the s protein have been mapped as the receptor-binding domain (rbd), which mediates binding to the sars-cov receptor angiotensin converting enzyme 2 (ace2) on sars-cov susceptible cells. in this study, we expressed a fusion protein containing the human codon-optimized rbd of the sars-cov spike protein linked to the fc portion of human igg1 (named rbd-fc) in he ...200818554741
a structural view of the inactivation of the sars coronavirus main proteinase by benzotriazole esters.the main proteinase (m(pro)) of the severe acute respiratory syndrome (sars) coronavirus is a principal target for the design of anticoronaviral compounds. benzotriazole esters have been reported as potent nonpeptidic inhibitors of the enzyme, but their exact mechanism of action remains unclear. here we present crystal structures of sars-cov m(pro), the active-site cysteine of which has been acylated by benzotriazole esters that act as suicide inhibitors. in one of the structures, the thioester ...200818559270
potent in vitro activity of the albumin fusion type 1 interferons (albumin-interferon-alpha and albumin-interferon-beta) against rna viral agents of bioterrorism and the severe acute respiratory syndrome (sars) virus.the type 1 interferons (inf-alpha and inf-beta) are potent antiviral agents. albumin-inf-alpha and albumin-inf-beta are novel recombinant proteins consisting of ifn-alpha or ifn-beta genetically fused to human albumin.200818560223
solution structure of the c-terminal dimerization domain of sars coronavirus nucleocapsid protein solved by the sail-nmr method.the c-terminal domain (ctd) of the severe acute respiratory syndrome coronavirus (sars-cov) nucleocapsid protein (np) contains a potential rna-binding region in its n-terminal portion and also serves as a dimerization domain by forming a homodimer with a molecular mass of 28 kda. so far, the structure determination of the sars-cov np ctd in solution has been impeded by the poor quality of nmr spectra, especially for aromatic resonances. we have recently developed the stereo-array isotope labelin ...200818561946
cathepsin l functionally cleaves the severe acute respiratory syndrome coronavirus class i fusion protein upstream of rather than adjacent to the fusion peptide.unlike other class i viral fusion proteins, spike proteins on severe acute respiratory syndrome coronavirus virions are uncleaved. as we and others have demonstrated, infection by this virus depends on cathepsin proteases present in endosomal compartments of the target cell, suggesting that the spike protein acquires its fusion competence by cleavage during cell entry rather than during virion biogenesis. here we demonstrate that cathepsin l indeed activates the membrane fusion function of the s ...200818562523
peptides from the sars-associated coronavirus as tags for protein expression and purification.protein tagging with a peptide is a commonly used technique to facilitate protein detection and to carry out protein purification. flexibility with respect to the peptide tag is essential since no single tag suites all purposes. this report describes the usage of two short peptides from the sars-associated coronavirus nucleocapsid (sars-n) protein as protein tags. plasmids for the generation of tagged proteins were generated by ligating synthetic oligonucleotides for the peptide-coding regions d ...200818565762
the management of coronavirus infections with particular reference to sars.the human coronaviruses (hcov) oc43 and 229e are common causes of upper respiratory tract infections. severe diseases were rare, however, until the emergence of the severe acute respiratory syndrome (sars)-cov in 2003. since then, other novel cov (nl63 and hku1) have been described, and they have caused respiratory infections worldwide. potentially exposed laboratory workers or animal handlers with rapidly progressive pneumonia not responding to standard antibacterial coverage must be isolated w ...200818565970
qm/qm studies for michael reaction in coronavirus main protease (3cl pro).severe acute respiratory syndrome (sars) is an illness caused by a novel corona virus wherein the main proteinase called 3cl(pro) has been established as a target for drug design. the mechanism of action involves nucleophilic attack by cys145 present in the active site on the carbonyl carbon of the scissile amide bond of the substrate and the intermediate product is stabilized by hydrogen bonds with the residues of the oxyanion hole. based on the x-ray structure of 3cl(pro) co-crystallized with ...200818567519
pathways of cross-species transmission of synthetically reconstructed zoonotic severe acute respiratory syndrome coronavirus.zoonotic severe acute respiratory syndrome coronavirus (sars-cov) likely evolved to infect humans by a series of transmission events between humans and animals in markets in china. virus sequence data suggest that the palm civet served as an amplification host in which civet and human interaction fostered the evolution of the epidemic sars urbani strain. the prototypic civet strain of sars-cov, sz16, was isolated from a palm civet but has not been successfully cultured in vitro. to propagate a c ...200818579604
high-throughput assay using a gfp-expressing replicon for sars-cov drug discovery.the causative agent of severe acute respiratory syndrome (sars) has been identified as a novel coronavirus, sars-cov. the development of rapid screening assays is essential for antiviral drug discovery. by using a cell line expressing a sars-cov subgenomic replicon, we developed a high-throughput assay and used it to screen small molecule compounds for inhibitors of sars-cov replication in the absence of live virus. the assay system involves minimal manipulation after assay set-up, facilitates a ...200818584889
pathology of experimental sars coronavirus infection in cats and ferrets.the pathology of severe acute respiratory syndrome-coronavirus (sars-cov) infection in cats and ferrets is poorly described, and the distribution of angiotensin-converting enzyme 2 (ace2), a receptor for sars-cov, in the respiratory tracts of these species is unknown. we observed sars-cov antigen expression and lesions in the respiratory tracts of 4 cats and 4 ferrets at 4 days postinoculation and ace2 expression in the respiratory tracts of 3 cats and 3 ferrets without infection. all infected c ...200818587105
wse, a new sequence distance measure based on word frequencies.in this article, we present a new distance metric, the weighted sequence entropy (wse), based on the short word composition of biological sequences. as a revision of the classical relative entropy (re), our metric (1) works equivalently with re in the case of small k, (2) avoids the degeneracy when some word types are absent in one sequence but not in the other. experiments on 25 viruses including sars-covs show that our method and re give exactly the same phylogenetic tree when word length k <o ...200818590747
severe acute respiratory syndrome coronavirus nucleocapsid protein confers ability to efficiently produce virus-like particles when substituted for the human immunodeficiency virus nucleocapsid domain.we replaced the hiv-1 nucleocapsid (nc) domain with different n-coding sequences to test sars-cov nucleocapsid (n) self-interaction capacity, and determined the capabilities of each chimera to direct virus-like particle (vlp) assembly. analysis results indicate that the replacement of nc with the carboxyl-terminal half of the sars-cov n resulted in the production of wild type (wt)-level virus-like particles (vlps) with the density of a wt hiv-1 particle. when co-expressed with sars-cov n, chimer ...200818592403
dc-sign mediates avian h5n1 influenza virus infection in cis and in trans.dc-sign, a c-type lectin receptor expressed in dendritic cells (dcs), has been identified as a receptor for human immunodeficiency virus type 1, hepatitis c virus, ebola virus, cytomegalovirus, dengue virus, and the sars coronavirus. we used h5n1 pseudotyped and reverse-genetics (rg) virus particles to study their ability to bind with dc-sign. electronic microscopy and functional assay results indicate that pseudotyped viruses containing both ha and na proteins express hemagglutination and are c ...200818593570
a single amino acid substitution in the s1 and s2 spike protein domains determines the neutralization escape phenotype of sars-cov.in response to sars-cov infection, neutralizing antibodies are generated against the spike (s) protein. determination of the active regions that allow viral escape from neutralization would enable the use of these antibodies for future passive immunotherapy. we immunized mice with uv-inactivated sars-cov to generate three anti-s monoclonal antibodies, and established several neutralization escape mutants with s protein. we identified several amino acid substitutions, including y442f and v601g in ...200818606245
development of broad-spectrum halomethyl ketone inhibitors against coronavirus main protease 3cl(pro).coronaviruses comprise a large group of rna viruses with diverse host specificity. the emergence of highly pathogenic strains like the sars coronavirus (sars-cov), and the discovery of two new coronaviruses, nl-63 and hku1, corroborates the high rate of mutation and recombination that have enabled them to cross species barriers and infect novel hosts. for that reason, the development of broad-spectrum antivirals that are effective against several members of this family is highly desirable. this ...200818611220
a second sars-cov s2 glycoprotein internal membrane-active peptide. biophysical characterization and membrane interaction.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. the s2 domain of protein s has been suggested to have two fusion peptides, one located at its n-terminus, downstream of the furin cleavage, and another, more internal, located immediately upstream of the hr1. therefore, we have carried out a study of the binding and interaction with mode ...200818616295
construction of a non-infectious sars coronavirus replicon for application in drug screening and analysis of viral protein function.severe acute respiratory syndrome virus (sars-cov) was the causative agent of the sars outbreaks in 2002-2003. a safer in vitro system is desirable for conducting research on sars-cov and to screen for antiviral drugs against the virus. based on the infectious cdna clone of rsars-cov-deltae, in which the e gene has been deleted, a safe non-infectious replicon was constructed by replacing the s gene with the enhanced green fluorescent protein (egfp) gene. successful replication was achieved as ev ...200818619943
a rapid point of care immunoswab assay for sars-cov detection.the emergence of severe acute respiratory syndrome (sars) resulted in several outbreaks worldwide. early tests for diagnosis were not always conclusive in identifying a sars suspected patient. nucleocapsid protein (np) is the most predominant virus derived structural protein which is shed in high amounts in serum and nasopharyngeal aspirate during the first week of infection. as part of such efforts, a simple, easy to use immunoswab method was developed by generating a panel of monoclonal antibo ...200818620761
virus-like particles of sars-like coronavirus formed by membrane proteins from different origins demonstrate stimulating activity in human dendritic cells.the pathogenesis of sars coronavirus (cov) remains poorly understood. in the current study, two recombinant baculovirus were generated to express the spike (s) protein of sars-like coronavirus (sl-cov) isolated from bats (vacbs) and the envelope (e) and membrane (m) proteins of sars-cov, respectively. co-infection of insect cells with these two recombinant baculoviruses led to self-assembly of virus-like particles (bvlps) as demonstrated by electron microscopy. incorporation of s protein of vacb ...200818628832
phosphorylation of the arginine/serine dipeptide-rich motif of the severe acute respiratory syndrome coronavirus nucleocapsid protein modulates its multimerization, translation inhibitory activity and cellular localization.coronavirus nucleocapsid protein is abundant in infected cells and participates in viral rna replication and transcription. the central domain of the nucleocapsid protein contains several arginine/serine (rs) dipeptides, the biological significance of which has not been well investigated. in the present study, we demonstrate that the severe acute respiratory syndrome coronavirus nucleocapsid protein is phosphorylated primarily within the rs-rich region in cells and by sr protein kinase 1 in vitr ...200818631359
the transmembrane domain of the severe acute respiratory syndrome coronavirus orf7b protein is necessary and sufficient for its retention in the golgi complex.the severe acute respiratory syndrome coronavirus (sars-cov) orf7b (also called 7b) protein is an integral membrane protein that is translated from a bicistronic open reading frame encoded within subgenomic rna 7. when expressed independently or during virus infection, orf7b accumulates in the golgi compartment, colocalizing with both cis- and trans-golgi markers. to identify the domains of this protein that are responsible for golgi localization, we have generated a set of mutant proteins and a ...200818632859
genomic analysis reveals age-dependent innate immune responses to severe acute respiratory syndrome coronavirus.the relationship between immunosenescence and the host response to virus infection is poorly understood at the molecular level. two different patterns of pulmonary host responses to virus were observed when gene expression profiles from severe acute respiratory syndrome coronavirus (sars-cov)-infected young mice that show minimal disease were compared to those from sars-cov-infected aged mice that develop pneumonitis. in young mice, genes related to cellular development, cell growth, and cell cy ...200818632870
severe acute respiratory syndrome coronavirus 3a protein activates the mitochondrial death pathway through p38 map kinase activation.the molecular mechanisms governing severe acute respiratory syndrome coronavirus-induced pathology are not fully understood. virus infection and some individual viral proteins, including the 3a protein, induce apoptosis. however, the cellular targets leading to 3a protein-mediated apoptosis have not been fully characterized. this study showed that the 3a protein modulates the mitochondrial death pathway in two possible ways. activation of caspase-8 through extrinsic signal(s) caused bid activati ...200818632968
structural flexibility of the pentameric sars coronavirus envelope protein ion channel.coronaviruses contain a small envelope membrane protein with cation-selective ion channel activity mediated by its transmembrane domain (etm). in a computational study, we proposed that ion channel activity can be explained by either of two similar etm homopentameric transmembrane alpha-helical bundles, related by a approximately 50 degrees rotation of the helices. later, we tested this prediction, using site-specific infrared dichroism of a lysine-flanked isotopically labeled etm peptide from t ...200818658207
bench-to-bedside review: rare and common viral infections in the intensive care unit--linking pathophysiology to clinical presentation.viral infections are common causes of respiratory tract disease in the outpatient setting but much less common in the intensive care unit. however, a finite number of viral agents cause respiratory tract disease in the intensive care unit. some viruses, such as influenza, respiratory syncytial virus (rsv), cytomegalovirus (cmv), and varicella-zoster virus (vzv), are relatively common. others, such as adenovirus, severe acute respiratory syndrome (sars)-coronavirus, hantavirus, and the viral hemo ...200818671826
animal models and vaccines for sars-cov infection.we summarize findings of sars-cov infections in several animal models each of which support viral replication in lungs accompanied by histopathological changes and/or clinical signs of illness to varying degrees. new findings are reported on sars-cov replication and associated pathology in two additional strains (c57bl/6 and 129s6) of aged mice. we also provide new comparative data on viral replication and associated pathology following infection of golden syrian hamsters with various sars-cov s ...200817499378
effectiveness of control measures during the sars epidemic in beijing: a comparison of the rt curve and the epidemic curve.one of the areas most affected by sars was beijing with 2521 reported cases. we estimate the effective reproductive number rt for the beijing sars epidemic, which represents the average number of secondary cases per primary case on each day of the epidemic and is therefore a measure of the underlying transmission dynamics. our results provide a quantitative assessment of the effectiveness of public health control measures. more generally, our results illustrate how changes in rt will reflect cha ...200817568476
expression of feline angiotensin converting enzyme 2 and its interaction with sars-cov s1 protein.feline angiotensin converting enzyme 2 (face2) gene was amplified from domestic cat lung with rt-pcr, cloned and sequenced. the complete coding region is 2418bp in length and is the closest to human ace2 among known ace2 homologs of non-primate animals. the n terminal fragment 19- 367 aa was expressed in escherishia coli. both western blotting and elisa demonstrated that face2 could react with sars-cov s1 protein as efficiently as ace2 of vero e6 cells did.200817658563
pathogenetic mechanisms of severe acute respiratory syndrome.severe acute respiratory syndrome (sars) is an acute respiratory disease with significant morbidity and mortality. while its clinical manifestations have been extensively studied, its pathogenesis is not yet fully understood. a limited number of autopsy studies have revealed that the lungs and the immune system are the organs that sustain the most severe damage. other organs affected include the kidneys, brain, digestive tract, heart, liver, thyroid gland and urogenital tract. the primary target ...200817825937
comments to the predecessor of human sars coronavirus in 2003-2004 epidemic. 200817884305
the sars-cov nucleocapsid protein: a protein with multifarious activities.ever since the discovery of sars-cov in the year 2003, numerous researchers around the world have been working relentlessly to understand the biology of this virus. as in other coronaviruses, nucleocapsid (n) is one of the most crucial structural components of the sars-cov. hence major attention has been focused on characterization of this protein. independent studies conducted by several laboratories have elucidated significant insight into the primary function of this protein, which is to enca ...200817881296
vaccination of mice with recombinant baculovirus expressing spike or nucleocapsid protein of sars-like coronavirus generates humoral and cellular immune responses.continuous efforts have been made to develop a prophylactic vaccine against severe acute respiratory syndrome coronavirus (sars-cov). in this study, two recombinant baculoviruses, vac-n and vac-s, were constructed, which contained the mammalian-cell activate promoter element, human elongation factor 1alpha-subunit (ef-1alpha), the human cytomegalovirus (cmv) immediate-early promoter, and the nucleocapsid (n) or spike (s) gene of bat sars-like cov (sl-cov) under the control of the cmv promoter. m ...200817905435
covdb: a comprehensive database for comparative analysis of coronavirus genes and genomes.the recent sars epidemic has boosted interest in the discovery of novel human and animal coronaviruses. by july 2007, more than 3000 coronavirus sequence records, including 264 complete genomes, are available in genbank. the number of coronavirus species with complete genomes available has increased from 9 in 2003 to 25 in 2007, of which six, including coronavirus hku1, bat sars coronavirus, group 1 bat coronavirus hku2, groups 2c and 2d coronaviruses, were sequenced by our laboratory. to overco ...200817913743
heptad repeat-derived peptides block protease-mediated direct entry from the cell surface of severe acute respiratory syndrome coronavirus but not entry via the endosomal pathway.the peptides derived from the heptad repeat (hrp) of severe acute respiratory syndrome coronavirus (scov) spike protein (shrps) are known to inhibit scov infection, yet their efficacies are fairly low. recently our research showed that some proteases facilitated scov's direct entry from the cell surface, resulting in a more efficient infection than the previously known infection via endosomal entry. to compare the inhibitory effect of the shrp in each pathway, we selected two shrps, which showed ...200817942557
transcriptional profiling of vero e6 cells over-expressing sars-cov s2 subunit: insights on viral regulation of apoptosis and proliferation.we have previously demonstrated that over-expression of spike protein (s) of severe acute respiratory syndrome coronavirus (sars-cov) or its c-terminal subunit (s2) is sufficient to induce apoptosis in vitro. to further investigate the possible roles of s2 in sars-cov-induced apoptosis and pathogenesis of sars, we characterized the host expression profiles induced upon s2 over-expression in vero e6 cells by oligonucleotide microarray analysis. possible activation of mitochondrial apoptotic pathw ...200817961624
molecular docking identifies the binding of 3-chloropyridine moieties specifically to the s1 pocket of sars-cov mpro.the 3c-like main proteinase of the severe acute respiratory syndrome (sars) coronavirus, sars-cov m(pro), is widely considered to be a major drug target for the development of anti-sars treatment. based on the chemical structure of a lead compound from a previous screening, we have designed and synthesized a number of non-peptidyl inhibitors, some of which have shown significantly improved inhibitory activity against sars-cov m(pro) with ic(50) values of approximately 60 nm. in the absence of sa ...200817931870
mutation of gly-11 on the dimer interface results in the complete crystallographic dimer dissociation of severe acute respiratory syndrome coronavirus 3c-like protease: crystal structure with molecular dynamics simulations.sars-cov 3c-like protease (3cl(pro)) is an attractive target for anti-severe acute respiratory syndrome (sars) drug discovery, and its dimerization has been extensively proved to be indispensable for enzymatic activity. however, the reason why the dissociated monomer is inactive still remains unclear due to the absence of the monomer structure. in this study, we showed that mutation of the dimer-interface residue gly-11 to alanine entirely abolished the activity of sars-cov 3cl(pro). subsequentl ...200817977841
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
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
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
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
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
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
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