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prevalence of sars-cov antibody in all hong kong patient contacts.the near absence of transmission (seroprevalence=0.19%) resulting in asymptomatic infection in this representative high-risk group of close contacts indicates that the prevailing sars-cov strains in hong kong almost always led to clinically apparent disease.200920393222
[human coronaviruses].coronaviruses are a large group of viruses and infect a lot of species of mammals and birds. five coronaviruses currently infect humans: hcovs 229e and oc43, identified in the 1960s, sars-cov identified in march 2003 during the sars epidemic, and the hcovs nl63 and hku1, identified in 2004 and 2005 respectively. the genome of the coronaviruses is a linear, non-segmented, positive-sense single-stranded rna molecule of approximately 30kb. the evolution of these viruses occurs through some features ...200918456429
protease-mediated entry via the endosome of human coronavirus 229e.human coronavirus 229e, classified as a group i coronavirus, utilizes human aminopeptidase n (apn) as a receptor; however, its entry mechanism has not yet been fully elucidated. we found that hela cells infected with 229e via apn formed syncytia when treated with trypsin or other proteases but not in a low-ph environment, a finding consistent with syncytium formation by severe acute respiratory syndrome coronavirus (sars-cov). in addition, trypsin induced cleavage of the 229e s protein. by using ...200918971274
differential activities of cellular and viral macro domain proteins in binding of adp-ribose metabolites.macro domain is a highly conserved protein domain found in both eukaryotes and prokaryotes. macro domains are also encoded by a set of positive-strand rna viruses that replicate in the cytoplasm of animal cells, including coronaviruses and alphaviruses. the functions of the macro domain are poorly understood, but it has been suggested to be an adp-ribose-binding module. we have here characterized three novel human macro domain proteins that were found to reside either in the cytoplasm and nucleu ...200918983849
identification of a minimal peptide derived from heptad repeat (hr) 2 of spike protein of sars-cov and combination of hr1-derived peptides as fusion inhibitors.the heptad repeats (hr1 and hr2) of the spike protein of sars-cov are highly conserved regions forming a critical 6-helix bundle during the fusion step of virus entry and are attractive targets of entry inhibitors. in this study, we report that a minimal hr2 peptide, p6 of 23-mer, can block the fusion of sars-cov with an ic(50) of 1.04+/-0.22 microm. this finding supports the structural prediction of the deep groove of hr1 trimer as a target for fusion inhibitors, and suggests p6 as a potential ...200918983873
conserved amino acids w423 and n424 in receptor-binding domain of sars-cov are potential targets for therapeutic monoclonal antibody.the receptor-binding domain (rbd) on spike protein of severe acute respiratory syndrome-associated coronavirus (sars-cov) is the main region interacting with the viral receptor-ace2 and is a useful target for induction of neutralizing antibodies against sars-cov infection. here we generated two monoclonal antibodies (mabs), targeting rbd, with marked virus neutralizing activity. the mabs recognize a new conformational epitope which consists of several discontinuous peptides (aa. 343-367, 373-390 ...200918986662
crystal structures of two coronavirus adp-ribose-1''-monophosphatases and their complexes with adp-ribose: a systematic structural analysis of the viral adrp domain.the coronaviruses are a large family of plus-strand rna viruses that cause a wide variety of diseases both in humans and in other organisms. the coronaviruses are composed of three main lineages and have a complex organization of nonstructural proteins (nsp's). in the coronavirus, nsp3 resides a domain with the macroh2a-like fold and adp-ribose-1"-monophosphatase (adrp) activity, which is proposed to play a regulatory role in the replication process. however, the significance of this domain for ...200918987156
humoral and cellular immune responses induced by 3a dna vaccines against severe acute respiratory syndrome (sars) or sars-like coronavirus in mice.vaccine development for severe acute respiratory syndrome coronavirus (sars-cov) has mainly focused on the spike (s) protein. however, the variation of the s gene between viruses may affect the efficacy of a vaccine, particularly for cross-protection against sars-like cov (sl-cov). recently, a more conserved group-specific open reading frame (orf), the 3a gene, was found in both sars-cov and sl-cov. here, we studied the immunogenicity of human sars-cov 3a and bat sl-cov 3a dna vaccines in mice t ...200918987164
simple tests for rapid detection of canine parvovirus antigen and canine parvovirus-specific antibodies.canine parvovirus (cpv) is the number one viral cause of enteritis, morbidity, and mortality in 8-week-old young puppies. we have developed twin assays (slide agglutination test [sat] for cpv antigen and slide inhibition test [sit] for cpv antibody) that are sensitive, specific, cost-effective, generic for all genotypes of cpv, and provide instant results for cpv antigen detection in feces and antibody quantification in serum. we found these assays to be useful for routine applications in kennel ...200918987166
broadening of neutralization activity to directly block a dominant antibody-driven sars-coronavirus evolution pathway.phylogenetic analyses have provided strong evidence that amino acid changes in spike (s) protein of animal and human sars coronaviruses (sars-covs) during and between two zoonotic transfers (2002/03 and 2003/04) are the result of positive selection. while several studies support that some amino acid changes between animal and human viruses are the result of inter-species adaptation, the role of neutralizing antibodies (nabs) in driving sars-cov evolution, particularly during intra-species transm ...200818989460
structural and biochemical investigation of heptad repeat derived peptides of human sars corona virus (hsars-cov) spike protein.hsars-cov is the causative agent for sars infection. its spike glycoprotein (s) is processed by host furin enzyme to produce s1 and s2 fragments, the latter being crucial for fusion with the host membrane. this takes place via formation of a coiled coil 6-helix bundle involving n and c-terminal heptad repeat domains (hr-n and hr-c) of s2. several fluorescent and non-fluorescent peptides from these domains were synthesized to examine their interactions by circular dichroism, thermal denaturation, ...200818991761
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
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
evaluation of cotton rats as a model for severe acute respiratory syndrome.experimental studies were conducted to evaluate two species of cotton rats, sigmodon hispidus and sigmodon fulviventer, as a model for severe acute respiratory syndrome (sars). blood and turbinate wash samples, and lung tissue were collected from each animal at different time points after sars coronavirus (cov) infection for determining the growth curve of virus, if any, by the standard infectivity assay in vero e6 cells. in addition, sections of the lung, liver, spleen, and kidney were taken an ...200818447621
evaluation of cotton rats as a model for severe acute respiratory syndrome.experimental studies were conducted to evaluate two species of cotton rats, sigmodon hispidus and sigmodon fulviventer, as a model for severe acute respiratory syndrome (sars). blood and turbinate wash samples, and lung tissue were collected from each animal at different time points after sars coronavirus (cov) infection for determining the growth curve of virus, if any, by the standard infectivity assay in vero e6 cells. in addition, sections of the lung, liver, spleen, and kidney were taken an ...200818447621
what caused lymphopenia in sars and how reliable is the lymphokine status in glucocorticoid-treated patients?severe acute respiratory syndrome (sars) outbreak in 2002-03 caused morbidity in over 8000 individuals and mortality in 744 in 29 countries. lymphopenia along with neutrophilia was a feature of sars, as it is in respiratory syncytial virus (rsv) and ebola infections, to name a few. direct infestation of lymphocytes, neutrophils and macrophages by sars coronavirus (cov) has been debated as a cause of lymphopenia, but there is no convincing data. lymphopenia can be caused by glucocorticoids, and t ...200818448259
the nucleocapsid protein of severe acute respiratory syndrome coronavirus inhibits cell cytokinesis and proliferation by interacting with translation elongation factor 1alpha.severe acute respiratory syndrome coronavirus (sars-cov) is the etiological agent of sars, an emerging disease characterized by atypical pneumonia. using a yeast two-hybrid screen with the nucleocapsid (n) protein of sars-cov as a bait, the c terminus (amino acids 251 to 422) of the n protein was found to interact with human elongation factor 1-alpha (ef1alpha), an essential component of the translational machinery with an important role in cytokinesis, promoting the bundling of filamentous acti ...200818448518
severe acute respiratory syndrome coronavirus protein 6 accelerates murine hepatitis virus infections by more than one mechanism.the severe acute respiratory syndrome coronavirus (sars-cov) encodes numerous accessory proteins whose importance in the natural infection process is currently unclear. one of these accessory proteins is set apart by its function in the context of a related murine hepatitis virus (mhv) infection. sars-cov protein 6 increases mhv neurovirulence and accelerates mhv infection kinetics in tissue culture. protein 6 also blocks nuclear import of macromolecules from the cytoplasm, a process known to in ...200818448520
structural analysis of major species barriers between humans and palm civets for severe acute respiratory syndrome coronavirus infections.it is believed that a novel coronavirus, severe acute respiratory syndrome coronavirus (sars-cov), was passed from palm civets to humans and caused the epidemic of sars in 2002 to 2003. the major species barriers between humans and civets for sars-cov infections are the specific interactions between a defined receptor-binding domain (rbd) on a viral spike protein and its host receptor, angiotensin-converting enzyme 2 (ace2). in this study a chimeric ace2 bearing the critical n-terminal helix fro ...200818448527
the discovery of angiotensin-converting enzyme 2 and its role in acute lung injury in mice.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, termed angiotensin-converting enzyme 2 (ace2), has been identified as a receptor for sars-cov. angiotensin-converting enzym ...200818448662
sirna silencing of angiotensin-converting enzyme 2 reduced severe acute respiratory syndrome-associated coronavirus replications in vero e6 cells.the outbreak of severe acute respiratory syndrome (sars) in 2002-2003 has had a significant impact worldwide. no effective prophylaxis or treatment for sars is available up to now. angiotensin-converting enzyme 2 (ace2) is the cellular receptor for sars-associated coronavirus (sars-cov). by expressing a u6 promoter-driven small interfering rna containing sequences homologous to part of ace2 mrna, we successfully silenced ace2 expression in vero e6 cells. by detecting negative strand sars-cov rna ...200818449585
sars-coronavirus replication/transcription complexes are membrane-protected and need a host factor for activity in vitro.sars-coronavirus (sars-cov) replication and transcription are mediated by a replication/transcription complex (rtc) of which virus-encoded, non-structural proteins (nsps) are the primary constituents. the 16 sars-cov nsps are produced by autoprocessing of two large precursor polyproteins. the rtc is believed to be associated with characteristic virus-induced double-membrane structures in the cytoplasm of sars-cov-infected cells. to investigate the link between these structures and viral rna synt ...200818451981
pathogenicity of severe acute respiratory coronavirus deletion mutants in hace-2 transgenic mice.recombinant severe acute respiratory virus (sars-cov) variants lacking the group specific genes 6, 7a, 7b, 8a, 8b and 9b (rsars-cov-delta[6-9b]), the structural gene e (rsars-cov-deltae), and a combination of both sets of genes (rsars-cov-delta[e,6-9b]) have been generated. all these viruses were rescued in monkey (vero e6) cells and were also infectious for human (huh-7, huh7.5.1 and caco-2) cell lines and for transgenic (tg) mice expressing the sars-cov receptor human angiotensin converting en ...200818452964
signal amplification on a dna-tile-based biosensor with enhanced sensitivity.aims: herein, we report our work to improve the detection sensitivity of a dna-tile-based and self-assembled biosensing platform. this was achieved using hybridization chain reaction (hcr) as a signal amplifier on a water-soluble self-assembled dna nanoarray carrying detection probes. materials & methods: the fluorescence enhancement on the addition of specific detection targets was observed directly by confocal fluorescence microscopy. results & discussion: the versatility of the system was dem ...200818694314
variable oligomerization modes in coronavirus non-structural protein 9.non-structural protein 9 (nsp9) of coronaviruses is believed to bind single-stranded rna in the viral replication complex. the crystal structure of nsp9 of human coronavirus (hcov) 229e reveals a novel disulfide-linked homodimer, which is very different from the previously reported nsp9 dimer of sars coronavirus. in contrast, the structure of the cys69ala mutant of hcov-229e nsp9 shows the same dimer organization as the sars-cov protein. in the crystal, the wild-type hcov-229e protein forms a tr ...200818694760
polymorphisms in the c-type lectin genes cluster in chromosome 19 and predisposition to severe acute respiratory syndrome coronavirus (sars-cov) infection.polymorphisms of clec4m have been associated with predisposition for infection by the severe acute respiratory syndrome coronavirus (sars-cov). dc-signr, a c-type lectin encoded by clec4m, is a receptor for the virus. a variable number tandem repeat (vntr) polymorphism in its neck region was recently associated with susceptibility to sars infection. however, this association was controversial and was not supported by subsequent studies. two explanations may account for this discrepancy: (1) ther ...200818697825
dissection and identification of regions required to form pseudoparticles by the interaction between the nucleocapsid (n) and membrane (m) proteins of sars coronavirus.when expressed in mammalian cells, the nucleocapsid (n) and membrane (m) proteins of the severe acute respiratory syndrome coronavirus (sars-cov) are sufficient to form pseudoparticles. to identify region(s) of the n molecule required for pseudoparticle formation, we performed biochemical analysis of the interaction of n mutants and m in hek293 cells. using a peptide library derived from n, we found that amino acids 101-115 constituted a novel binding site for m. we examined the ability of n mut ...200818703211
molecular dynamic simulations analysis of ritonavir and lopinavir as sars-cov 3cl(pro) inhibitors.since the emergence of the severe acute respiratory syndrome (sars) to date, neither an effective antiviral drug nor a vaccine against sars is available. however, it was found that a mixture of two hiv-1 proteinase inhibitors, lopinavir and ritonavir, exhibited some signs of effectiveness against the sars virus. to understand the fine details of the molecular interactions between these proteinase inhibitors and the sars virus via complexation, molecular dynamics simulations were carried out for ...200818706430
a sars-cov protein, orf-6, induces caspase-3 mediated, er stress and jnk-dependent apoptosis.severe acute respiratory syndrome (sars) coronavirus (cov) spread from china to more than 30 countries, causing severe outbreaks of atypical pneumonia and over 800 deaths worldwide. cov primarily infects the upper respiratory and gastrointestinal tract; however, sars-cov has a unique pathogenesis because it infects both the upper and lower respiratory tracts and leads to human respiratory diseases. sars-cov genome has shown containing 14 open reading frames (orfs) and 8 of them encode novel prot ...200818708124
expression and functional characterisation of the putative sars coronavirus non-structural proteins x1-x5.1. we produced mammalian expression vectors encoding the sars coronavirus (sars-cov) accessory proteins with or without the fluorescence protein tag and cell lines with stable expression of these proteins. 2. the cellular localisation and function of the sars-cov accessory proteins was determined. 3. sars 6 and sars 8b proteins are localised to the endoplasmic reticulum and nucleus/cytoplasm, respectively, and both proteins stimulate host cell dna synthesis.200818708666
sars coronavirus and apoptosis.1. the adenovirus-mediated overexpression of sars coronavirus (sars-cov) spike protein (s) and its c-terminal domain (s2) induce apoptosis in vero e6 cells. 2. such apoptosis in vero e6 cells is time- and dose-dependent. 3. the adenovirus-mediated overexpression of sars-cov n-terminal domain (s1) and other structural proteins, including e,m and n protein, do not induce apoptosis.200818708667
molecular and genetic characterisation of the sars coronavirus auxiliary protein x1 in drosophila.1. we have generated monoclonal antibodies against the sars coronavirus (sars-cov) x1/3a protein (3a), which are suitable for western blotting, immunocytochemistry, and immunohistochemistry. 2. we have established and characterised an in-vivo 3a transgenic drosophila model, and demonstrated its usefulness in studying sars-cov 3a gene function. 3. we validated our in-vivo findings on 3a gene function in mammalian vero e6 cells. 4. our findings raise the possibility of using ion channel blockers a ...200818708668
risk-stratified seroprevalence of sars coronavirus in children residing in a district with point-source outbreak compared to a low-risk area.1. sars coronavirus has low transmissibility at the community level. 2. subclinical sars coronavirus infection is rare in children.200818708669
mechanisms of lymphocyte loss in sars coronavirus infection.1. human lymphocytes and monocytes are not permissive to productive sars coronavirus (sars-cov) infection in vitro. 2. challenge of lymphocytes and monocytes with infectious sars-cov, inactivated virions, and receptor-binding fragment of spike protein does not trigger apoptosis. 3. direct infection/interaction between viruses and lymphocytes/monocytes is unlikely to be the cause of lymphopaenia in sars patients. 4. lymphopaenia in sars patients is likely to result from indirect mechanisms second ...200818708670
investigation of immunogenic t-cell epitopes in sars virus nucleocapsid protein and their role in the prevention and treatment of sars infection.1. a novel hla-a2.1-specific sars coronavirus (sars-cov) nucleocapsid (n) protein epitope (n220-n228 lalllldrl) able to activate cytotoxic t cells in vitro has been identified. 2. when used with a single-chain-trimer system, the sars-cov n protein epitope (n220-n228 lalllldrl) can stimulate a cytotoxic t-cell response against n-protein expressing cells in the hla-a2.1k(b) transgenic mouse model.200818708671
role of polymorphisms of the inflammatory response genes and dc-signr in genetic susceptibility to sars and other infections.1. a genetic risk-association study involving more than 1200 subjects showed individuals homozygous for l-sign tandem repeats are less susceptible to sars infection. 2. this was supported by in vitro binding studies that demonstrated homozygous l-sign, compared to heterozygous, had higher binding capacity for sars coronavirus (sars-cov), with higher proteasome-dependent viral degradation. in contrast, homozygous l-sign demonstrated lower binding capacity for hiv1-gp120.3. genetic-association stu ...200818708672
helicases as antiviral drug targets.1. we have demonstrated for the first time that the helicase of a ribonucleic acid virus, the sars coronavirus (sars-cov), is a valid target for drug development. 2. using high throughput screen and chemical synthesis, several lead compounds targeting the sars-cov helicase have been identified. we have shown that these compounds can inhibit sars-cov helicase activity and viral growth in cell culture systems. these compounds can potentially be used to target other viruses.200818708673
studies of sars virus vaccines.1. intranasal vaccination using inactivated sars coronavirus (sars-cov) vaccine with adjuvant can induce strong systemic (serum immunoglobulin [ig] g) and respiratory tract local (tracheal-lung wash fluid iga) antibody responses with neutralising activity. 2. rbd-fc (protein-based vaccine) is able to induce effective neutralising antibodies able to provide protection from sars-cov infection in animal models. 3. a single dose of rbd-raav vaccination can induce adequate neutralising antibody again ...200818708674
an evaluation of sars and droplet infection control practices in acute and rehabilitation hospitals in hong kong.1. this study has demonstrated that great efforts have been made by the hospital authority and the studied hospital cluster to contain and prevent infection, and that high levels of vigilance have been enforced in anticipation of future outbreaks of sars and other droplet infections. 2. most health care workers and support workers have good hospital infection control and isolation precaution knowledge levels. 3. compliance with infection control guidelines is satisfactory and has increased compa ...200818708675
membrane insertion of the three main membranotropic sequences from sars-cov s2 glycoprotein.in order to complete the fusion process of sars-cov virus, several regions of the s2 virus envelope glycoprotein are necessary. recent studies have identified three membrane-active regions in the s2 domain of sars-cov glycoprotein, one situated downstream of the minimum furin cleavage, which is considered the fusion peptide (sarsfp), an internal fusion peptide located immediately upstream of the hr1 region (sarsifp) and the pre-transmembrane domain (sarsptm). we have explored the capacity of the ...200818721794
development of human single-chain antibodies against sars-associated coronavirus.the outbreak of severe acute respiratory syndrome (sars), caused by a distinct coronavirus, in 2003 greatly threatened public health in china, southeast asia as well as north america. over 1,000 patients died of the sars virus, representing 10% of infected people. like other coronaviruses, the sars virus also utilizes a surface glycoprotein, namely the spike protein, to infect host cells. the spike protein of sars virus consists of 1,255 amino acid residues and can be divided into two sub-domain ...200818724064
the m, e, and n structural proteins of the severe acute respiratory syndrome coronavirus are required for efficient assembly, trafficking, and release of virus-like particles.the production of virus-like particles (vlps) constitutes a relevant and safe model to study molecular determinants of virion egress. the minimal requirement for the assembly of vlps for the coronavirus responsible for severe acute respiratory syndrome in humans (sars-cov) is still controversial. recent studies have shown that sars-cov vlp formation depends on either m and e proteins or m and n proteins. here we show that both e and n proteins must be coexpressed with m protein for the efficient ...200818753196
severe acute respiratory syndrome vaccine efficacy in ferrets: whole killed virus and adenovirus-vectored vaccines.although the 2003 severe acute respiratory syndrome (sars) outbreak was controlled, repeated transmission of sars coronavirus (cov) over several years makes the development of a sars vaccine desirable. we performed a comparative evaluation of two sars vaccines for their ability to protect against live sars-cov intranasal challenge in ferrets. both the whole killed sars-cov vaccine (with and without alum) and adenovirus-based vectors encoding the nucleocapsid (n) and spike (s) protein induced neu ...200818753223
[antiviral activity of arbidol and its derivatives against the pathogen of severe acute respiratory syndrome in the cell cultures].experimental studies of arbidol and arbidol mesylate versus ribavirin suggest that insertion of these agents into the nutrient medium of the cultured cells gmk-ah-1 (d) after infection at concentrations of 50, 25, and 100 microg/ml, respectively, is effective in suppressing the reproduction of severe acute respiratory syndrome (sars) virus. arbidol and arbidol mesylate were shown to have a direct antiviral effect in early viral replication in the cultured cells. the promising antiviral agent is ...200818756809
steroid-induced osteonecrosis: the number of lesions is related to the dosage.severe acute respiratory syndrome (sars) is a newly described infectious disease caused by the sars coronavirus which attacks the immune system and pulmonary epithelium. it is treated with regular high doses of corticosteroids. our aim was to determine the relationship between the dosage of steroids and the number and distribution of osteonecrotic lesions in patients treated with steroids during the sars epidemic in beijing, china in 2003. we identified 114 patients for inclusion in the study. o ...200818757967
an immunosuppressed syrian golden hamster model for sars-cov infection.several small animal models have been developed for the study of severe acute respiratory syndrome coronavirus (sars-cov) replication and pathogenesis. syrian golden hamsters are among the best small animal models, though little clinical illness and no mortality are observed after virus infection. cyclophosphamide was used to immunosuppress hamsters leading to a prolonged disease course and higher mortality after sars-cov infection. in addition, there was a significant weight loss, expanded tiss ...200818760437
an immunosuppressed syrian golden hamster model for sars-cov infection.several small animal models have been developed for the study of severe acute respiratory syndrome coronavirus (sars-cov) replication and pathogenesis. syrian golden hamsters are among the best small animal models, though little clinical illness and no mortality are observed after virus infection. cyclophosphamide was used to immunosuppress hamsters leading to a prolonged disease course and higher mortality after sars-cov infection. in addition, there was a significant weight loss, expanded tiss ...200818760437
toona sinensis roem tender leaf extract inhibits sars coronavirus replication.severe acute respiratory syndrome (sars) is a life-threatening disease caused by the sars coronavirus (sars-cov). the development of new antiviral agents for sars-cov is an important issue. we tried to find potential resource from traditional chinese medicine (tcm) for development of new drugs against sars-cov.200818762235
severe acute respiratory syndrome coronavirus elicits a weak interferon response compared to traditional interferon-inducing viruses.the aim of the present study is to investigate changes of interferon (ifn) production occurring over the first 48 h after infection of peripheral blood mononuclear cells (pbmcs) with severe acute respiratory syndrome (sars) coronavirus (cov) and to compare these changes to those induced by well-established ifn-inducing viruses, such as vesicular stomatitis (vsv) and newcastle viruses (ndv). experiments have been carried out using pbmcs of 10 different healthy donors. the results showed that the ...200818781076
entry from the cell surface of severe acute respiratory syndrome coronavirus with cleaved s protein as revealed by pseudotype virus bearing cleaved s protein.severe acute respiratory syndrome (sars) coronavirus (sars-cov) is known to take an endosomal pathway for cell entry; however, it is thought to enter directly from the cell surface when a receptor-bound virion spike (s) protein is affected by trypsin, which induces cleavage of the s protein and activates its fusion potential. this suggests that sars-cov bearing a cleaved form of the s protein can enter cells directly from the cell surface without trypsin treatment. to explore this possibility, w ...200818786990
interactions between m protein and other structural proteins of severe, acute respiratory syndrome-associated coronavirus.severe acute respiratory syndrome-associated coronavirus (sars-cov) structural proteins (s, e, m, and nc) localize in different subcellular positions when expressed individually. however, sars-cov m protein is co-localized almost entirely with s, e, or nc protein when co-expressed in the cells. on the other hand, only partial co-localization was observed when s and e, s and nc, or e and nc were co-expressed in the cells. interactions between sars-cov m and other structural proteins but not inter ...200818792806
design, synthesis and antiviral efficacy of a series of potent chloropyridyl ester-derived sars-cov 3clpro inhibitors.design, synthesis and biological evaluation of a series of 5-chloropyridine ester-derived severe acute respiratory syndrome-coronavirus chymotrypsin-like protease inhibitors is described. position of the carboxylate functionality is critical to potency. inhibitor 10 with a 5-chloropyridinyl ester at position 4 of the indole ring is the most potent inhibitor with a sars-cov 3clpro ic(50) value of 30 nm and an antiviral ec(50) value of 6.9 microm. molecular docking studies have provided possible b ...200818796354
sars-coronavirus replication is supported by a reticulovesicular network of modified endoplasmic reticulum.positive-strand rna viruses, a large group including human pathogens such as sars-coronavirus (sars-cov), replicate in the cytoplasm of infected host cells. their replication complexes are commonly associated with modified host cell membranes. membrane structures supporting viral rna synthesis range from distinct spherular membrane invaginations to more elaborate webs of packed membranes and vesicles. generally, their ultrastructure, morphogenesis, and exact role in viral replication remain to b ...200818798692
rhesus angiotensin converting enzyme 2 supports entry of severe acute respiratory syndrome coronavirus in chinese macaques.angiotensin converting enzyme 2 (ace2) is the receptor that severe acute respiratory syndrome coronavirus (sars-cov) utilizes for target cell entry and, therefore, plays an important role in sars pathogenesis. since chinese rhesus (rh) macaques do not usually develop sars after sars-cov infection, it has been suggested that rh-ace2 probably does not support viral entry efficiently. to determine the role of rh-ace2 in early lung pathogenesis in vivo, we studied eleven chinese rhesus monkeys exper ...200818801550
rhesus angiotensin converting enzyme 2 supports entry of severe acute respiratory syndrome coronavirus in chinese macaques.angiotensin converting enzyme 2 (ace2) is the receptor that severe acute respiratory syndrome coronavirus (sars-cov) utilizes for target cell entry and, therefore, plays an important role in sars pathogenesis. since chinese rhesus (rh) macaques do not usually develop sars after sars-cov infection, it has been suggested that rh-ace2 probably does not support viral entry efficiently. to determine the role of rh-ace2 in early lung pathogenesis in vivo, we studied eleven chinese rhesus monkeys exper ...200818801550
a prime-boost vaccination protocol optimizes immune responses against the nucleocapsid protein of the sars coronavirus.severe acute respiratory syndrome (sars) is a serious infectious disease caused by the sars coronavirus. we assessed the potential of prime-boost vaccination protocols based on the nucleocapsid (nc) protein co-administered with a derivative of the mucosal adjuvant malp-2 or expressed by modified vaccinia virus ankara (mva-nc) to stimulate humoral and cellular immune responses at systemic and mucosal levels. the obtained results demonstrated that strong immune responses can be elicited both at sy ...200818805454
risk factors for sars infection within hospitals in hanoi, vietnam.we investigated a nosocomial infection of severe acute respiratory syndrome (sars) in vietnam in 2003 and attempted to identify risk factors for sars infection. of the 146 subjects who came into contact with sars patients at hospital a, 43 (29.5%) developed sars, and an additional 16 (11%) were asymptomatic but sars-coronavirus (cov) seropositive. the asymptomatic infection rate accounted for 15.5% of the total number of infected patients at hospital a, which was higher than that of 6.5% observe ...200818806349
importance of cholesterol-rich membrane microdomains in the interaction of the s protein of sars-coronavirus with the cellular receptor angiotensin-converting enzyme 2.cholesterol present in the plasma membrane of target cells has been shown to be important for the infection by sars-cov. we show that cholesterol depletion by treatment with methyl-beta-cyclodextrin (m beta cd) affects infection by sars-cov to the same extent as infection by vesicular stomatitis virus-based pseudotypes containing the surface glycoprotein s of sars-cov (vsv-delta g-s). therefore, the role of cholesterol for sars-cov infection can be assigned to the s protein and is unaffected by ...200818814896
systematic assembly of a full-length infectious clone of human coronavirus nl63.historically, coronaviruses were predominantly associated with mild upper respiratory disease in humans. more recently, three novel coronaviruses associated with severe human respiratory disease were found, including (i) the severe acute respiratory syndrome coronavirus, associated with a significant atypical pneumonia and 10% mortality; (ii) hku-1, associated with chronic pulmonary disease; and (iii) nl63, associated with both upper and lower respiratory tract disease in children and adults wor ...200818818320
inhibition of the interaction between the sars-cov spike protein and its cellular receptor by anti-histo-blood group antibodies.severe acute respiratory syndrome coronavirus (sars-cov) is a highly pathogenic emergent virus which replicates in cells that can express abh histo-blood group antigens. the heavily glycosylated sars-cov spike (s) protein binds to angiotensin-converting enzyme 2 which serves as a cellular receptor. epidemiological analysis of a hospital outbreak in hong kong revealed that blood group o was associated with a low risk of infection. in this study, we used a cellular model of adhesion to investigate ...200818818423
inhibition of the interaction between the sars-cov spike protein and its cellular receptor by anti-histo-blood group antibodies.severe acute respiratory syndrome coronavirus (sars-cov) is a highly pathogenic emergent virus which replicates in cells that can express abh histo-blood group antigens. the heavily glycosylated sars-cov spike (s) protein binds to angiotensin-converting enzyme 2 which serves as a cellular receptor. epidemiological analysis of a hospital outbreak in hong kong revealed that blood group o was associated with a low risk of infection. in this study, we used a cellular model of adhesion to investigate ...200818818423
new respiratory viruses of humans.acute respiratory viruses are a major cause of morbidity and mortality in humans worldwide and most acute respiratory infections are caused by viruses. many of these viruses cause the highest burden of disease in specific risk groups such as young infants, the elderly, and immune-compromised individuals. although the most important respiratory viruses of humans have been identified in the last century, in the past decade about a dozen "new" viruses have been discovered that may cause a high burd ...200818820582
a sars dna vaccine induces neutralizing antibody and cellular immune responses in healthy adults in a phase i clinical trial.the severe acute respiratory syndrome (sars) virus is a member of the coronaviridae (cov) family that first appeared in the guangdong province of china in 2002 and was recognized as an emerging infectious disease in march 2003. over 8000 cases and 900 deaths occurred during the epidemic. we report the safety and immunogenicity of a sars dna vaccine in a phase i human study.200818824060
design and synthesis of cinanserin analogs as severe acute respiratory syndrome coronavirus 3cl protease inhibitors.the severe acute respiratory syndrome (sars) coronavirus 3cl protease is an attractive target for the development of anti-sars drugs. in this paper, cinanserin (1) analogs were synthesized and tested for the inhibitory activities against sars-coronavirus (cov) 3cl protease by fluorescence resonance energy transfer (fret) assay. four analogs show significant activities, especially compound 26 with an ic(50) of 1.06 microm.200818827378
genome-wide analysis of protein-protein interactions and involvement of viral proteins in sars-cov replication.analyses of viral protein-protein interactions are an important step to understand viral protein functions and their underlying molecular mechanisms. in this study, we adopted a mammalian two-hybrid system to screen the genome-wide intraviral protein-protein interactions of sars coronavirus (sars-cov) and therefrom revealed a number of novel interactions which could be partly confirmed by in vitro biochemical assays. three pairs of the interactions identified were detected in both directions: no ...200818827877
t cell responses to whole sars coronavirus in humans.effective vaccines should confer long-term protection against future outbreaks of severe acute respiratory syndrome (sars) caused by a novel zoonotic coronavirus (sars-cov) with unknown animal reservoirs. we conducted a cohort study examining multiple parameters of immune responses to sars-cov infection, aiming to identify the immune correlates of protection. we used a matrix of overlapping peptides spanning whole sars-cov proteome to determine t cell responses from 128 sars convalescent samples ...200818832706
topology and membrane anchoring of the coronavirus replication complex: not all hydrophobic domains of nsp3 and nsp6 are membrane spanning.coronaviruses express two very large replicase polyproteins, the 16 autoproteolytic cleavage products of which collectively form the membrane-anchored replication complexes. how these structures are assembled is still largely unknown, but it is likely that the membrane-spanning members of these nonstructural proteins (nsps) are responsible for the induction of the double-membrane vesicles and for anchoring the replication complexes to these membranes. for 3 of the 16 coronavirus nsps-nsp3, nsp4, ...200818842706
evaluation of peptide-aldehyde inhibitors using r188i mutant of sars 3cl protease as a proteolysis-resistant mutant.the 3c-like (3cl) protease of the severe acute respiratory syndrome (sars) coronavirus is a key enzyme for the virus maturation. we found for the first time that the mature sars 3cl protease is subject to degradation at 188arg/189gln. replacing arg with ile at position 188 rendered the protease resistant to proteolysis. the r188i mutant digested a conserved undecapeptide substrate with a k(m) of 33.8 microm and k(cat) of 4753 s(-1). compared with the value reported for the mature protease contai ...200818845442
a noncovalent class of papain-like protease/deubiquitinase inhibitors blocks sars virus replication.we report the discovery and optimization of a potent inhibitor against the papain-like protease (plpro) from the coronavirus that causes severe acute respiratory syndrome (sars-cov). this unique protease is not only responsible for processing the viral polyprotein into its functional units but is also capable of cleaving ubiquitin and isg15 conjugates and plays a significant role in helping sars-cov evade the human immune system. we screened a structurally diverse library of 50,080 compounds for ...200818852458
sars coronavirus: unusual lability of the nucleocapsid protein.the severe acute respiratory syndrome (sars) is a contagious disease that killed hundreds and sickened thousands of people worldwide between november 2002 and july 2003. the nucleocapsid (n) protein of the coronavirus responsible for this disease plays a critical role in viral assembly and maturation and is of particular interest because of its potential as an antiviral target or vaccine candidate. refolding of sars n-protein during production and purification showed the presence of two addition ...200818926799
interaction of severe acute respiratory syndrome-coronavirus and nl63 coronavirus spike proteins with angiotensin converting enzyme-2.although in different groups, the coronaviruses severe acute respiratory syndrome-coronavirus (sars-cov) and nl63 use the same receptor, angiotensin converting enzyme (ace)-2, for entry into the host cell. despite this common receptor, the consequence of entry is very different; severe respiratory distress in the case of sars-cov but frequently only a mild respiratory infection for nl63. using a wholly recombinant system, we have investigated the ability of each virus receptor-binding protein, s ...200818931070
[sars vaccines].severe acute respiratory syndrome (sars) is an emerging disease derived from wild animals and is highly pathogenic with a high mortality. a novel coronavirus sars coronavirus was identified to be a causative agent for sars. since its discovery, many trials have been executed to establish the prophylactic and therapeutics toward sars using laboratory animals. a number of different types of vaccines, such as inactivated virus vaccine, subunit vaccine, dna vaccine and vaccine using viral expression ...200818939499
prior immunization with severe acute respiratory syndrome (sars)-associated coronavirus (sars-cov) nucleocapsid protein causes severe pneumonia in mice infected with sars-cov.the details of the mechanism by which severe acute respiratory syndrome-associated coronavirus (sars-cov) causes severe pneumonia are unclear. we investigated the immune responses and pathologies of sars-cov-infected balb/c mice that were immunized intradermally with recombinant vaccinia virus (vv) that expressed either the sars-cov spike (s) protein (lc16m8rvv-s) or simultaneously all the structural proteins, including the nucleocapsid (n), membrane (m), envelope (e), and s proteins (lc16m8rvv- ...200818941225
emerging and zoonotic infections in women.emerging infections, many zoonotic, are caused by a variety of pathogens with global distribution. previously rare pathogens have emerged; global travel facilitates their rapid spread. human encroachment on remote areas has brought contact with zoonotic diseases never before characterized. although systematic study of rare outbreaks can be challenging, knowledge of emerging pathogens and their effects on women is accumulating. this article discusses effects of lymphocytic choriomeningitis virus, ...200818954762
detection of antibodies against sars-coronavirus using recombinant truncated nucleocapsid proteins by elisa.severe acute respiratory syndrome (sars) is a lifethreatening emerging respiratory disease caused by the coronavirus, sars-cov. the nucleocapsid (n) protein of sars-cov is highly antigenic and may be a suitable candidate for diagnostic applications. we constructed truncated recombinant n proteins (n1 [1-422 aa], n2 [1- 109 aa], and n3 [110-422 aa]) and determined their antigenicity by western blotting using convalescent sars serum. the recombinants containing n1 and n3 reacted with convalescent ...200818955825
plp2, a potent deubiquitinase from murine hepatitis virus, strongly inhibits cellular type i interferon production.infections by coronaviruses such as severe acute respiratory syndrome (sars) coronavirus (scov) and mouse hepatitis virus a59 (mhv-a59) result in very little type i interferon (ifn) production by host cells, which is potentially responsible for the rapid viral growth and severe immunopathology associated with sars. however, the molecular mechanisms for the low ifn production in cells infected with coronaviruses remain unclear. here, we provide evidence that papain-like protease domain 2 (plp2), ...200818957937
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
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