Publications

TitleAbstractYear(sorted ascending)
Filter
PMID
Filter
crystal structure of nl63 respiratory coronavirus receptor-binding domain complexed with its human receptor.nl63 coronavirus (nl63-cov), a prevalent human respiratory virus, is the only group i coronavirus known to use angiotensin-converting enzyme 2 (ace2) as its receptor. incidentally, ace2 is also used by group ii sars coronavirus (sars-cov). we investigated how different groups of coronaviruses recognize the same receptor, whereas homologous group i coronaviruses recognize different receptors. we determined the crystal structure of nl63-cov spike protein receptor-binding domain (rbd) complexed wit ...200919901337
micrornome analysis unravels the molecular basis of sars infection in bronchoalveolar stem cells.severe acute respiratory syndrome (sars), caused by the coronavirus sars-cov, is an acute infectious disease with significant mortality. a typical clinical feature associated with sars is pulmonary fibrosis and associated lung failure. in the aftermath of the sars epidemic, although significant progress towards understanding the underlying molecular mechanism of the infection has been made, a large gap still remains in our knowledge regarding how sars-cov interacts with the host cell at the onse ...200919915717
cleavage of the sars coronavirus spike glycoprotein by airway proteases enhances virus entry into human bronchial epithelial cells in vitro.entry of enveloped viruses into host cells requires the activation of viral envelope glycoproteins through cleavage by either intracellular or extracellular proteases. in order to gain insight into the molecular basis of protease cleavage and its impact on the efficiency of viral entry, we investigated the susceptibility of a recombinant native full-length s-protein trimer (trispike) of the severe acute respiratory syndrome coronavirus (sars-cov) to cleavage by various airway proteases.200919924243
antibody binding site mapping of sars-cov spike protein receptor-binding domain by a combination of yeast surface display and phage peptide library screening.the receptor-binding domain (rbd) of severe acute respiratory syndrome coronavirus (sars-cov) spike (s) protein plays an important role in viral infection, and is a potential major neutralizing determinant. in this study, three hybridoma cell lines secreting specific monoclonal antibodies against the rbd of the s protein were generated and their exact binding sites were identified. using yeast surface display, the binding sites of these antibodies were defined to two linear regions on the rbd: s ...200919951177
protein transfer enhances cellular immune responses to dna vaccination against sars-cov.the current dna vaccine formulations are not optimal for stimulation of cd8(+) t cells, which are required for clearing virally-infected cells. here we show that cd8(+) t cell-stimulating activity can be effectively augmented by combining dna vaccination with protein transfer. c57bl/6 mice were injected intramuscularly with an anti-sars-cov dna vaccine admixed with a lipid-derived conjugate of 4-1bbl, a potential cd8(+) t-cell co-stimulator. the inclusion of the lipidated co-stimulator greatly e ...200919951178
host-pathogen interactions during coronavirus infection of primary alveolar epithelial cells.viruses that infect the lung are a significant cause of morbidity and mortality in animals and humans worldwide. coronaviruses are being associated increasingly with severe diseases in the lower respiratory tract. alveolar epithelial cells are an important target for coronavirus infection in the lung, and infected cells can initiate innate immune responses to viral infection. in this overview, we describe in vitro models of highly differentiated alveolar epithelial cells that are currently being ...200919638499
severe acute respiratory syndrome coronavirus nonstructural protein 2 interacts with a host protein complex involved in mitochondrial biogenesis and intracellular signaling.the severe acute respiratory syndrome coronavirus (sars-cov) generates 16 nonstructural proteins (nsp's) through proteolytic cleavage of a large precursor protein. although several nsp's exhibit catalytic activities that are important for viral replication and transcription, other nsp's have less clearly defined roles during an infection. in order to gain a better understanding of their functions, we attempted to identify host proteins that interact with nsp's during sars-cov infections. for nsp ...200919640993
mesodynamics in the sars nucleocapsid measured by nmr field cycling.protein motions on all timescales faster than molecular tumbling are encoded in the spectral density. the dissection of complex protein dynamics is typically performed using relaxation rates determined at high and ultra-high field. here we expand this range of the spectral density to low fields through field cycling using the nucleocapsid protein of the sars coronavirus as a model system. the field-cycling approach enables site-specific measurements of r (1) at low fields with the sensitivity an ...200919641854
structure-based design, synthesis, and biological evaluation of a series of novel and reversible inhibitors for the severe acute respiratory syndrome-coronavirus papain-like protease.we describe here the design, synthesis, molecular modeling, and biological evaluation of a series of small molecule, nonpeptide inhibitors of sars-cov plpro. our initial lead compound was identified via high-throughput screening of a diverse chemical library. we subsequently carried out structure-activity relationship studies and optimized the lead structure to potent inhibitors that have shown antiviral activity against sars-cov infected vero e6 cells. upon the basis of the x-ray crystal struct ...200919645480
evaluating protein similarity from coarse structures.to unscramble the relationship between protein function and protein structure, it is essential to assess the protein similarity from different aspects. although many methods have been proposed for protein structure alignment or comparison, alternative similarity measures are still strongly demanded due to the requirement of fast screening and query in large-scale structure databases. in this paper, we first formulate a novel representation of a protein structure, i.e., feature sequence of surfac ...200919875857
unraveling the complexities of the interferon response during sars-cov infection.viruses employ different strategies to circumvent the antiviral actions of the innate immune response. sars coronavirus (sars-cov), a virus that causes severe lung damage, encodes an array of proteins able to inhibit induction and signaling of type-i interferons. however, recent studies have demonstrated that interferons are produced during sars-cov infection in humans and macaques. furthermore, nuclear translocation of activated stat1 and a range of interferon-stimulated genes could be demonstr ...200919885368
mutagenesis of the transmembrane domain of the sars coronavirus spike glycoprotein: refinement of the requirements for sars coronavirus cell entry.the spike protein (s) of sars coronavirus (sars-cov) mediates entry of the virus into target cells, including receptor binding and membrane fusion. close to or in the viral membrane, the s protein contains three distinct motifs: a juxtamembrane aromatic part, a central highly hydrophobic stretch and a cysteine rich motif. here, we investigate the role of aromatic and hydrophobic parts of s in the entry of sars cov and in cell-cell fusion. this was investigated using the previously described sars ...200920034394
engineering a novel endopeptidase based on sars 3cl(pro).a 3c-like protease (3clpro) from the severe acute respiratory syndrome-coronavirus (sars-cov) is required for viral replication, cleaving the replicase polyproteins at 11 sites with the conserved gln [downward arrow](ser, ala, gly) sequences. in this study, we developed a mutant 3clpro (t25g) with an expanded s1' space that demonstrates 43.5-fold better k(cat)/k(m) compared with wild-type in cleaving substrates with a larger met at p1' and is suitable for tag removal from recombinant fusion prot ...200920041855
data mining pathogen genomes using geneorder and coregenes and cgug: gene order, synteny and in silico proteomes.sequence databases are growing exponentially due to 'next generation' dna analysers and applications of these data. databases include multiple sequences of previously sequenced organisms, particularly ones of consequence to human health. applications are limited by tools available to mine them, particularly user-friendly tools that are useful for bench researchers. geneorder, coregenes and cgug are web-based 'on-the-fly' tools that examine gene order and synteny, as well as proteomes for compara ...200920054988
establishment, immortalisation and characterisation of pteropid bat cell lines.bats are the suspected natural reservoir hosts for a number of new and emerging zoonotic viruses including nipah virus, hendra virus, severe acute respiratory syndrome coronavirus and ebola virus. since the discovery of sars-like coronaviruses in chinese horseshoe bats, attempts to isolate a sl-cov from bats have failed and attempts to isolate other bat-borne viruses in various mammalian cell lines have been similarly unsuccessful. new stable bat cell lines are needed to help with these investig ...200920011515
establishment, immortalisation and characterisation of pteropid bat cell lines.bats are the suspected natural reservoir hosts for a number of new and emerging zoonotic viruses including nipah virus, hendra virus, severe acute respiratory syndrome coronavirus and ebola virus. since the discovery of sars-like coronaviruses in chinese horseshoe bats, attempts to isolate a sl-cov from bats have failed and attempts to isolate other bat-borne viruses in various mammalian cell lines have been similarly unsuccessful. new stable bat cell lines are needed to help with these investig ...200920011515
anti-sars coronavirus 3c-like protease effects of rheum palmatum l. extracts.the present study aims to clarify the inhibitive effect of the compounds from rheum palmatum l. on the sars-3cl protease. the sars-cov 3cl gene was amplified from rna of the sars virus by pcr. the sars-cov 3cl protease was purified from a colon bacillus recombinant. drugs and 3cl protease were incubated together. the inhibition rate and ic(50) were calculated based on absorbance. components from the rheum palmatum l. had a high level of anti-sars-cov 3cl protease activity. the ic(50) was 13.76 + ...200920103835
detection of severe acute respiratory syndrome (sars) coronavirus nucleocapsid protein in human serum using a localized surface plasmon coupled fluorescence fiber-optic biosensor.in order to enhance the sensitivity of conventional immunoassay technology for the detection of sars coronavirus (sars-cov) nucleocapsid protein (n protein), we developed a localized surface plasmon coupled fluorescence (lspcf) fiber-optic biosensor that combines sandwich immunoassay with the lsp technique. experimentally, a linear relationship between the fluorescence signal and the concentration of recombinant sars-cov n (gst-n) protein in buffer solution could be observed from 0.1 pg/ml to 1 ...200919660929
shuffling multivariate adaptive regression splines and adaptive neuro-fuzzy inference system as tools for qsar study of sars inhibitors.in this work, the inhibitory activity of pyridine n-oxide derivatives against human severe acute respiratory syndrome (sars) is predicted in terms of quantitative structure-activity relationship (qsar) models. these models were developed with the aid of multivariate adaptive regression spline (mars) and adaptive neuro-fuzzy inference system (anfis) combined with shuffling cross-validation technique. a shuffling mars algorithm is utilized to select the most important variables in qsar modeling an ...200919665859
recombinant receptor-binding domain of sars-cov spike protein expressed in mammalian, insect and e. coli cells elicits potent neutralizing antibody and protective immunity.severe acute respiratory syndrome (sars) is a newly emerging infectious disease. the potential recurrence of the disease from animal reservoirs highlights the significance of development of safe and efficient vaccines to prevent a future sars epidemic. in this study, we expressed the recombinant receptor-binding domain (rrbd) in mammalian (293t) cells, insect (sf9) cells, and e. coli, respectively, and compared their immunogenicity and protection against sars-cov infection in an established mous ...200919683779
rna aptamer-based sensitive detection of sars coronavirus nucleocapsid protein.severe acute respiratory syndrome coronavirus (sars-cov) is the etiological agent of a newly emerged disease sars. the sars-cov nucleocapsid (n) protein is one of the most abundant structural proteins and serves as a diagnostic marker for accurate and sensitive detection of the virus. using a selex (systematic evolution of ligand by exponential enrichment) procedure and recombinant n protein, we selected a high-affinity rna aptamer capable of binding to n protein with a dissociation constant of ...200919684916
potential enhancement of osteoclastogenesis by severe acute respiratory syndrome coronavirus 3a/x1 protein.severe acute respiratory syndrome coronavirus (sars-cov) causes a lung disease with high mortality. in addition, osteonecrosis and bone abnormalities with reduced bone density have been observed in patients following recovery from sars, which were partly but not entirely explained by the short-term use of steroids. here, we demonstrate that human monocytes, potential precursors of osteoclasts, partly express angiotensin converting enzyme 2 (ace2), a cellular receptor of sars-cov, and that expres ...200919685004
avian influenza virus, streptococcus suis serotype 2, severe acute respiratory syndrome-coronavirus and beyond: molecular epidemiology, ecology and the situation in china.the outbreak and spread of severe acute respiratory syndrome-associated coronavirus and the subsequent identification of its animal origin study have heightened the world's awareness of animal-borne or zoonotic pathogens. in addition to sars, the highly pathogenic avian influenza virus (aiv), h5n1, and the lower pathogenicity h9n2 aiv have expanded their host ranges to infect human beings and other mammalian species as well as birds. even the 'well-known' reservoir animals for influenza virus, m ...200919687041
the antiviral action of common household disinfectants and antiseptics against murine hepatitis virus, a potential surrogate for sars coronavirus.the 2003 outbreak of severe acute respiratory syndrome (sars) infected over 8000 people and killed 774. transmission of sars occurred through direct and indirect contact and large droplet nuclei. the world health organization recommended the use of household disinfectants, which have not been previously tested against sars coronavirus (sars-cov), to disinfect potentially contaminated environmental surfaces. there is a need for a surrogate test system given the limited availability of the sars-co ...200919692148
temporal variability and social heterogeneity in disease transmission: the case of sars in hong kong.the extent to which self-adopted or intervention-related changes in behaviors affect the course of epidemics remains a key issue for outbreak control. this study attempted to quantify the effect of such changes on the risk of infection in different settings, i.e., the community and hospitals. the 2002-2003 severe acute respiratory syndrome (sars) outbreak in hong kong, where 27% of cases were healthcare workers, was used as an example. a stochastic compartmental seir (susceptible-exposed-infecti ...200919696879
reverse genetic characterization of the natural genomic deletion in sars-coronavirus strain frankfurt-1 open reading frame 7b reveals an attenuating function of the 7b protein in-vitro and in-vivo.during the outbreak of sars in 2002/3, a prototype virus was isolated from a patient in frankfurt/germany (strain frankfurt-1). as opposed to all other sars-coronavirus strains, frankfurt-1 has a 45-nucleotide deletion in the transmembrane domain of its orf 7b protein. when over-expressed in hek 293 cells, the full-length protein but not the variant with the deletion caused interferon beta induction and cleavage of procaspase 3. to study the role of orf 7b in the context of virus replication, we ...200919698190
reverse genetic characterization of the natural genomic deletion in sars-coronavirus strain frankfurt-1 open reading frame 7b reveals an attenuating function of the 7b protein in-vitro and in-vivo.during the outbreak of sars in 2002/3, a prototype virus was isolated from a patient in frankfurt/germany (strain frankfurt-1). as opposed to all other sars-coronavirus strains, frankfurt-1 has a 45-nucleotide deletion in the transmembrane domain of its orf 7b protein. when over-expressed in hek 293 cells, the full-length protein but not the variant with the deletion caused interferon beta induction and cleavage of procaspase 3. to study the role of orf 7b in the context of virus replication, we ...200919698190
two-step conformational changes in a coronavirus envelope glycoprotein mediated by receptor binding and proteolysis.the coronaviruses mouse hepatitis virus type 2 (mhv-2) and severe acute respiratory syndrome coronavirus (sars-cov) utilize proteases to enter host cells. upon receptor binding, the spike (s) proteins of both viruses are activated for membrane fusion by proteases, such as trypsin, present in the environment, facilitating virus entry from the cell surface. in contrast, in the absence of extracellular proteases, these viruses can enter cells via an endosomal pathway and utilize endosomal cathepsin ...200919706706
rhesus theta-defensin prevents death in a mouse model of severe acute respiratory syndrome coronavirus pulmonary disease.we evaluated the efficacy of rhesus theta-defensin 1 (rtd-1), a novel cyclic antimicrobial peptide, as a prophylactic antiviral in a mouse model of severe acute respiratory syndrome (sars) coronavirus (cov) lung disease. balb/c mice exposed to a mouse-adapted strain of sars-cov demonstrated 100% survival and modest reductions in lung pathology without reductions in virus titer when treated with two intranasal doses of rtd-1, while mortality in untreated mice was approximately 75%. rtd-1-treated, ...200919710146
sars-coronavirus spike s2 domain flanked by cysteine residues c822 and c833 is important for activation of membrane fusion.the s2 domain of the coronavirus spike (s) protein is known to be responsible for mediating membrane fusion. in addition to a well-recognized cleavage site at the s1-s2 boundary, a second proteolytic cleavage site has been identified in the severe acute respiratory syndrome coronavirus (sars-cov) s2 domain (r797). c-terminal to this s2 cleavage site is a conserved region flanked by cysteine residues c822 and c833. here, we investigated the importance of this well conserved region for sars-cov s- ...200919717178
american chemical society fall meeting, 16-20 august, washington, d.c. sugary achilles' heel raises hope for broad-acting antiviral drugs. 200919729635
commentary on the feature article. 200919736875
[study on interaction between sars-cov n and map19].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 n protein was found to interact with map19, a non-enzymatic protein of masp(mannan-associated serine protease). the interaction between sars-cov n and map19 would be further tested in cells in this article.200919737459
efficient induction of cytotoxic t lymphocytes specific for severe acute respiratory syndrome (sars)-associated coronavirus by immunization with surface-linked liposomal peptides derived from a non-structural polyprotein 1a.spike and nucleocapsid are structural proteins of severe acute respiratory syndrome (sars)-associated coronavirus (sars-cov) and major targets for cytotoxic t lymphocytes (ctls). in contrast, non-structural proteins encoded by two-thirds of viral genome are poorly characterized for cell-mediated immunity. we previously demonstrated that nucleocapsid-derived peptides chemically coupled to the surface of liposomes effectively elicited sars-cov-specific ctls in mice. here, we attempted to identify ...200919748524
human monoclonal antibodies to sars-coronavirus inhibit infection by different mechanisms.sars-cov causes an acute infection making targeted passive immunotherapy an attractive treatment strategy. we previously generated human mabs specific to the s1 region of sars-cov s protein. these mabs bind epitopes within the receptor binding domain (rbd) or upstream of the rbd. we show that mabs recognizing epitopes within the rbd inhibit infection by preventing viral attachment to the cellular receptor. one mab binds upstream of the rbd and prevents viral entry by inhibiting a post-binding ev ...200919748648
[the cloning, expression and structural analysis of putative unknown protein orf 9b in sars-cov].orf 9b was amplified by pcr from sars-cov genome and cloned into the nco i and bam hi sites of the pet32c expression vector, and then recombinant plasmid pet32c-orf 9b was constructed. the recombinant fusion protein orf 9b was expressed by iptg induction and purifed. after being cleaved by rek, orf 9b protein with mw 11 kd was separated and collected. it was demonstrated by elisa that the purified orf 9b protein could react with sera of sars rehabilitaion patients but not with sera from healthy ...200919769160
inducible bronchus-associated lymphoid tissue elicited by a protein cage nanoparticle enhances protection in mice against diverse respiratory viruses.destruction of the architectural and subsequently the functional integrity of the lung following pulmonary viral infections is attributable to both the extent of pathogen replication and to the host-generated inflammation associated with the recruitment of immune responses. the presence of antigenically disparate pulmonary viruses and the emergence of novel viruses assures the recurrence of lung damage with infection and resolution of each primary viral infection. thus, there is a need to develo ...200919774076
just like sars. 200919774678
signal from noise? 200919775957
coronavirus n protein n-terminal domain (ntd) specifically binds the transcriptional regulatory sequence (trs) and melts trs-ctrs rna duplexes.all coronaviruses (covs), including the causative agent of severe acute respiratory syndrome (sars), encode a nucleocapsid (n) protein that harbors two independent rna binding domains of known structure, but poorly characterized rna binding properties. we show here that the n-terminal domain (ntd) of n protein from mouse hepatitis virus (mhv), a virus most closely related to sars-cov, employs aromatic amino acid-nucleobase stacking interactions with a triple adenosine motif to mediate high-affin ...200919782089
distant relatives of severe acute respiratory syndrome coronavirus and close relatives of human coronavirus 229e in bats, ghana.we tested 12 bat species in ghana for coronavirus (cov) rna. the virus prevalence in insectivorous bats (n = 123) was 9.76%. cov was not detected in 212 fecal samples from eidolon helvum fruit bats. leaf-nosed bats pertaining to hipposideros ruber by morphology had group 1 and group 2 covs. virus concentrations were < or =45,000 copies/100 mg of bat feces. the diversified group 1 cov shared a common ancestor with the human common cold virus hcov-229e but not with hcov-nl63, disputing hypotheses ...200919788804
distant relatives of severe acute respiratory syndrome coronavirus and close relatives of human coronavirus 229e in bats, ghana.we tested 12 bat species in ghana for coronavirus (cov) rna. the virus prevalence in insectivorous bats (n = 123) was 9.76%. cov was not detected in 212 fecal samples from eidolon helvum fruit bats. leaf-nosed bats pertaining to hipposideros ruber by morphology had group 1 and group 2 covs. virus concentrations were < or =45,000 copies/100 mg of bat feces. the diversified group 1 cov shared a common ancestor with the human common cold virus hcov-229e but not with hcov-nl63, disputing hypotheses ...200919788804
phylogenetic perspectives on the epidemiology and origins of sars and sars-like coronaviruses.severe acute respiratory syndrome (sars) is a respiratory disease caused by a zoonotic coronavirus (cov) named sars-cov (scov), which rapidly swept the globe after its emergence in rural china during late 2002. the origins of scov have been mysterious and controversial, until the recent discovery of sars-like cov (slcov) in bats and the proposal of bats as the natural reservior of the coronaviridae family. in this article, we focused on discussing how phylogenetics contributed to our understandi ...200919800030
dual effect of nitric oxide on sars-cov replication: viral rna production and palmitoylation of the s protein are affected.nitric oxide is an important molecule playing a key role in a broad range of biological process such as neurotransmission, vasodilatation and immune responses. while the anti-microbiological properties of nitric oxide-derived reactive nitrogen intermediates (rni) such as peroxynitrite, are known, the mechanism of these effects are as yet poorly studied. severe acute respiratory syndrome coronavirus (sars-cov) belongs to the family coronaviridae, was first identified during 2002-2003. mortality i ...200919800091
determination of the functions of the putative metal-binding domain of the scv helicase. 200919801711
the macrophage in the pathogenesis of severe acute respiratory syndrome coronavirus infection. 200919801713
identification of human cell line model of persistent sars coronavirus infection and studies of the response to cytokines and chemokines. 200919801717
dynamics of sars-coronavirus hr2 domain in the prefusion and transition states.the envelope glycoproteins s1 and s2 of severe acute respiratory syndrome coronavirus (sars-cov) mediate viral entry by conformational change from a prefusion state to a postfusion state that enables fusion of the viral and target membranes. in this work we present the characterization of the dynamic properties of the sars-cov s2-hr2 domain (residues 1141-1193 of s) in the prefusion and newly discovered transition states by nmr (15)n relaxation studies. the dynamic properties of the different st ...200919819173
nuclear magnetic resonance structure of the nucleic acid-binding domain of severe acute respiratory syndrome coronavirus nonstructural protein 3.the nuclear magnetic resonance (nmr) structure of a globular domain of residues 1071 to 1178 within the previously annotated nucleic acid-binding region (nab) of severe acute respiratory syndrome coronavirus nonstructural protein 3 (nsp3) has been determined, and n- and c-terminally adjoining polypeptide segments of 37 and 25 residues, respectively, have been shown to form flexibly extended linkers to the preceding globular domain and to the following, as yet uncharacterized domain. this extensi ...200919828617
a two-pronged strategy to suppress host protein synthesis by sars coronavirus nsp1 protein.severe acute respiratory syndrome coronavirus nsp1 protein suppresses host gene expression, including type i interferon production, by promoting host mrna degradation and inhibiting host translation, in infected cells. we present evidence that nsp1 uses a novel, two-pronged strategy to inhibit host translation and gene expression. nsp1 bound to the 40s ribosomal subunit and inactivated the translational activity of the 40s subunits. furthermore, the nsp1-40s ribosome complex induced the modifica ...200919838190
evasion by stealth: inefficient immune activation underlies poor t cell response and severe disease in sars-cov-infected mice.severe acute respiratory syndrome caused substantial morbidity and mortality during the 2002-2003 epidemic. many of the features of the human disease are duplicated in balb/c mice infected with a mouse-adapted version of the virus (ma15), which develop respiratory disease with high morbidity and mortality. here, we show that severe disease is correlated with slow kinetics of virus clearance and delayed activation and transit of respiratory dendritic cells (rdc) to the draining lymph nodes (dln) ...200919851468
a new mouse-adapted strain of sars-cov as a lethal model for evaluating antiviral agents in vitro and in vivo.severe acute respiratory syndrome (sars) is a highly lethal emerging disease caused by coronavirus sars-cov. new lethal animal models for sars were needed to facilitate antiviral research. we adapted and characterized a new strain of sars-cov (strain v2163) that was highly lethal in 5- to 6-week-old balb/c mice. it had nine mutations affecting 10 amino acid residues. strain v2163 increased il-1alpha, il-6, mip-1alpha, mcp-1, and rantes in mice, and high il-6 expression correlated with mortality. ...200919853271
identification of a new region of sars-cov s protein critical for viral entry.infection by severe acute respiratory syndrome coronavirus (sars-cov) is initiated by specific interactions between the sars-cov spike (s) protein and its receptor ace2. in this report, we screened a peptide library representing the sars-cov s protein sequence using a human immunodeficiency virus-based pseudotyping system to identify specific regions that affect viral entry. one of the 169 peptides screened, peptide 9626 (s residues 217-234), inhibited sars-cov s-mediated entry of the pseudotype ...200919853613
the application of genomics to emerging zoonotic viral diseases.interspecies transmission of pathogens may result in the emergence of new infectious diseases in humans as well as in domestic and wild animals. genomics tools such as high-throughput sequencing, mrna expression profiling, and microarray-based analysis of single nucleotide polymorphisms are providing unprecedented ways to analyze the diversity of the genomes of emerging pathogens as well as the molecular basis of the host response to them. by comparing and contrasting the outcomes of an emerging ...200919855817
antibody-mediated synergy and interference in the neutralization of sars-cov at an epitope cluster on the spike protein.incomplete neutralization of virus, especially when it occurs in the presence of excess neutralizing antibody, represents a biological phenomenon that impacts greatly on antibody-mediated immune prophylaxis of viral infection and on successful vaccine design. to understand the mechanism by which a virus escapes from antibody-mediated neutralization, we have investigated the interactions of non-neutralizing and neutralizing antibodies at an epitope cluster on the spike protein of severe acute res ...200919861118
automated detection of conformational epitopes using phage display peptide sequences.precise determination of conformational epitopes of neutralizing antibodies represents a key step in the rational design of novel vaccines. a powerful experimental method to gain insights on the physical chemical nature of conformational epitopes is the selection of linear peptides that bind with high affinities to a monoclonal antibody of interest by phage display technology. however, the structural characterization of conformational epitopes from these mimotopes is not straightforward, and in ...200920140073
infectivity of severe acute respiratory syndrome during its incubation period.to evaluate the infectivity of severe acute respiratory syndrome (sars) during its incubation period by investigating chains of transmission and individuals isolated for medical observation with a view to providing scientific evidence for updating protocols of medical isolation.200920337224
is systems biology the key to preventing the next pandemic?sporadic outbreaks of epizootics including sars coronavirus and h5n1 avian influenza remind us of the potential for communicable diseases to quickly spread into worldwide epidemics. to confront emerging viral threats, nations have implemented strategies to prepare for pandemics and to control virus spread. despite improved surveillance and quarantine measures, we find ourselves in the midst of a h1n1 influenza pandemic. effective therapeutics and vaccines are essential to protect against current ...200920352075
immunogenetic studies in sars: developing a clinical prognostic profile for severe diseases. 200920393204
sars diagnosis, monitoring and prognostication by sars-coronavirus rna detection. 200920393205
functional roles of 3a protein in the pathogenesis of sars. 200920393207
correlation of clinical outcomes and radiographic features in sars patients. 200920393209
epidemiology of sars in the 2003 hong kong epidemic.1. the temporal and spatial evolution of the sars epidemic in hong kong is described. 2. estimates of key epidemiological distributions and their stability over the course of the epidemic are derived. 3. the characteristics of those who contracted the disease are determined including factors associated with the likelihood of mortality as a result of sars coronavirus infection.200920393218
viral loads in clinical specimens and sars manifestations.1. a high viral load in nasopharyngeal aspirate (with or without a high viral load in serum) is a useful prognostic indicator of respiratory failure or mortality. the presence of viral rna in multiple body sites is also indicative of poor prognosis. 2. early treatment with an effective antiviral agent before day 10 may decrease the peak viral load, and thus ameliorate the clinical symptoms and mortality, and reduce viral shedding and the risk of transmission200920393220
comparative host gene transcription by microarray analysis early after infection of the huh7 cell line by sars coronavirus and human coronavirus 229e.during the early stages of infection, sars-cov produces more severe perturbation of host cell gene expression in a human epithelial cell line of liver origin than the hcov-229e.200920393221
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
[cell entry mechanisms of coronaviruses].enveloped viruses enter into cells via fusion of their envelope and cellular membrane. spike (s) protein of coronavirus (cov) is responsible for entry events. we studied the cell entry mechanisms of two different covs, murine coronavirus mouse hepatitis virus (mhv) and severe acute respiratory syndrome coronavirus (sars-cov). mhv-jhm that induces syncytia in infected cells entered directly from cell surface, i.e., fusion of envelope and plasma membrane, whereas sars-cov and mhv-2 that fail to in ...200920218330
[progress in structural studies of larger proteins by the sail-nmr method]. 200921089580
the sars coronavirus 3a protein causes endoplasmic reticulum stress and induces ligand-independent downregulation of the type 1 interferon receptor.the severe acute respiratory syndrome coronavirus (sars-cov) is reported to cause apoptosis of infected cells and several of its proteins including the 3a accessory protein, are pro-apoptotic. since the 3a protein localizes to the endoplasmic reticulum (er)-golgi compartment, its role in causing er stress was investigated in transiently transfected cells. cells expressing the 3a proteins showed er stress based on activation of genes for the er chaperones grp78 and grp94. since er stress can caus ...200920020050
[occupationally acquired infections among health care workers: respiratory diseases].in some medical departments, healthcare workers (hcws) are at risk for aerogene transmitted infectious diseases. numerous fatal causalities were described in the international environment. for example fatal causalities during the sars-epidemic as well as cases of death caused by influenza.200932288301
synthesis in escherichia coli cells and characterization of the active exoribonuclease of severe acute respiratory syndrome coronavirus.the nsp14 protein, an exoribonuclease of the dedd superfamily encoded by severe acute respiratory syndrome coronavirus (sars-cov), was expressed in fusion with different affinity tags. the recombinant nsp14 proteins with either gst fusion or 6-histidine tag were shown to possess ribonuclease activity but nsp14 with a short mghhhhhhgs tag sequence at the n-terminus increased the solubility of nsp14 protein and facilitated the protein purification. mutations of the conserved residues of nsp14 resu ...200932214468
influenza, respiratory syncytial virus and sars.acute lower respiratory tract infections (lrtis) are a major worldwide health problem, particularly in childhood. about 30-50% of acute lrtis are viral in origin; of these, influenza and respiratory syncytial virus are associated with the greatest disease burden in humans. many different influenza a viruses occur naturally in animal reservoirs, and present a constant threat of zoonotic infections and global pandemics. the pandemic (h1n1) influenza virus that emerged in humans in 2009 contained a ...200932288570
low genetic diversity in the masked palm civet paguma larvata (viverridae).the masked palm civet is distributed through south-east asia, china and the himalayas. because of its potential role in the severe acute respiratory syndrome (sars) epidemic, it has become important to gather information on this species, and notably to provide a tool to determine the origin of farm and market animals. for this purpose, we studied the genetic variability and the phylogeographic pattern of the masked palm civet paguma larvata. first, two portions of mitochondrial genes, cytochrome ...200932336891
low genetic diversity in the masked palm civet paguma larvata (viverridae).the masked palm civet is distributed through south-east asia, china and the himalayas. because of its potential role in the severe acute respiratory syndrome (sars) epidemic, it has become important to gather information on this species, and notably to provide a tool to determine the origin of farm and market animals. for this purpose, we studied the genetic variability and the phylogeographic pattern of the masked palm civet paguma larvata. first, two portions of mitochondrial genes, cytochrome ...200932336891
immunotherapy of sars based on combinations of neutralizing human monoclonal antibodies.evaluation of: coughlin mm, babcook j, prabhakar bs: human monoclonal antibodies to sars-coronavirus inhibit infection by different mechanisms. virology 394(1), 39-46 (2009). this work discusses passive immunotherapy based on neutralizing human monoclonal antibodies (mabs) with different mechanisms of action. the authors have demonstrated that combining such mabs, which target distinct epitopes, may greatly increase inhibition of virus infection and suppress the generation of neutralization esca ...201032201501
parameter inference in small world network disease models with approximate bayesian computational methods.small world network models have been effective in capturing the variable behaviour of reported case data of the sars coronavirus outbreak in hong kong during 2003. simulations of these models have previously been realized using informed "guesses" of the proposed model parameters and tested for consistency with the reported data by surrogate analysis. in this paper we attempt to provide statistically rigorous parameter distributions using approximate bayesian computation sampling methods. we find ...201032288082
broad-spectrum in vitro activity and in vivo efficacy of the antiviral protein griffithsin against emerging viruses of the family coronaviridae.viruses of the family coronaviridae have recently emerged through zoonotic transmission to become serious human pathogens. the pathogenic agent responsible for severe acute respiratory syndrome (sars), the sars coronavirus (sars-cov), is a member of this large family of positive-strand rna viruses that cause a spectrum of disease in humans, other mammals, and birds. since the publicized outbreaks of sars in china and canada in 2002-2003, significant efforts successfully identified the causative ...201020032190
single-dose intranasal administration with mdef201 (adenovirus vectored mouse interferon-alpha) confers protection from mortality in a lethal sars-cov balb/c mouse model.interferons (ifns) are a first line of defense against viral infection. herein we describe the use of an adenovirus vectored mouse ifn alpha gene (mdef201) as a prophylactic and treatment countermeasure in a sars-cov-infected balb/c mouse model. complete survival protection was observed in mice given a single dose of mdef201 administered intranasally 1, 3, 5, 7, or 14 days prior to lethal sars-cov challenge (p<0.001), and body weights of these treated mice were unaffected by the challenge. in ad ...201021093489
sars - my personal battle.it isn't every day that a doctor becomes a patient. it is more peculiar when it occurs with an unknown mysterious epidemic respiratory illness that kills. severe acute respiratory syndrome (sars) gripped the world in 2003, spreading via air-links and throwing the global economy into disarray. as a practicing physician in singapore, one of the first countries affected, i describe my first-hand account of my battle with this illness, how i acquired this illness in singapore, and eventually quarant ...201021094092
effects of air temperature and relative humidity on coronavirus survival on surfaces.assessment of the risks posed by severe acute respiratory syndrome (sars) coronavirus (sars-cov) on surfaces requires data on survival of this virus on environmental surfaces and on how survival is affected by environmental variables, such as air temperature (at) and relative humidity (rh). the use of surrogate viruses has the potential to overcome the challenges of working with sars-cov and to increase the available data on coronavirus survival on surfaces. two potential surrogates were evaluat ...201020228108
induction of interferon-gamma-inducible protein 10 by sars-cov infection, interferon alfacon 1 and interferon inducer in human bronchial epithelial calu-3 cells and balb/c mice.the pathogenesis of severe acute respiratory syndrome coronavirus (sars-cov) is poorly understood. several mechanisms involving both direct effects on target cells and indirect effects via the immune system might exist. sars-cov has been shown in vitro to induce changes of cytokines and chemokines in various human and animal cells. we previously reported that interferon (ifn) alfacon-1 was more active against sars-cov infection in human bronchial epithelial calu-3 cells than in african green mon ...201020231782
induction of interferon-gamma-inducible protein 10 by sars-cov infection, interferon alfacon 1 and interferon inducer in human bronchial epithelial calu-3 cells and balb/c mice.the pathogenesis of severe acute respiratory syndrome coronavirus (sars-cov) is poorly understood. several mechanisms involving both direct effects on target cells and indirect effects via the immune system might exist. sars-cov has been shown in vitro to induce changes of cytokines and chemokines in various human and animal cells. we previously reported that interferon (ifn) alfacon-1 was more active against sars-cov infection in human bronchial epithelial calu-3 cells than in african green mon ...201020231782
lambda interferon renders epithelial cells of the respiratory and gastrointestinal tracts resistant to viral infections.virus-infected cells secrete a broad range of interferons (ifn) which confer resistance to yet uninfected cells by triggering the synthesis of antiviral factors. the relative contributions of the various ifn subtypes to innate immunity against virus infections remain elusive. ifn-alpha, ifn-beta, and other type i ifn molecules signal through a common, universally expressed cell surface receptor, whereas type iii ifn (ifn-lambda) uses a distinct cell-type-specific receptor complex for signaling. ...201020335250
identification of key amino acid residues required for horseshoe bat angiotensin-i converting enzyme 2 to function as a receptor for severe acute respiratory syndrome coronavirus.angiotensin-i converting enzyme 2 (ace2) is the receptor for severe acute respiratory syndrome (sars) coronavirus (sars-cov). a previous study indicated that ace2 from a horseshoe bat, the host of a highly related sars-like coronavirus, could not function as a receptor for sars-cov. here, we demonstrate that a 3 aa change from she (aa 40-42) to fyq was sufficient to convert the bat ace2 into a fully functional receptor for sars-cov. we further demonstrate that an ace2 molecule from a fruit bat, ...201020335495
the route of inoculation determines the tissue tropism of modified vaccinia tiantan expressing the spike glycoprotein of sars-cov in mice.the live replication-competent modified vaccinia virus tiantan (mvtt) is an attractive vaccine vector, yet little is known about its tissue tropism and pathology in vivo. recently, we demonstrated that a recombinant mvtt expressing the spike glycoprotein of sars-cov (namely mvtt-s) is superior to the non-replicating modified vaccinia ankara (mva-s) for inducing high level of neutralizing antibodies through mucosal vaccination. in this study, we further determined the tissue tropism and safety of ...201020336714
cd8+ t cell response in hla-a*0201 transgenic mice is elicited by epitopes from sars-cov s protein.cytotoxic cd8(+) t lymphocytes (ctls) play an important role in antiviral immunity. several human hla-a*0201 restricted ctl epitopes of severe acute respiratory syndrome (sars) spike (s) protein have been identified in hla-a*0201 transgenic (tg) mice, but the mechanisms and properties of immune responses are still not well understood. in this study, hla-a*0201 tg mice were primed intramuscularly with sars s dna and boosted subcutaneously with hla-a*0201 restricted peptides. the lymphocytes from ...201020709007
nmr structure of the sars-cov nonstructural protein 7 in solution at ph 6.5.the nmr structure of the severe acute respiratory syndrome coronavirus nonstructural protein (nsp) 7 in aqueous solution at ph 6.5 was determined and compared with the results of previous structure determinations of nsp7 in solution at ph 7.5 and in the crystals of a hexadecameric nsp7/nsp8 complex obtained from a solution at ph 7.5. all three structures contain four helices as the only regular secondary structures, but there are differences in the lengths and sequence locations of the four heli ...201020709084
identification of phenanthroindolizines and phenanthroquinolizidines as novel potent anti-coronaviral agents for porcine enteropathogenic coronavirus transmissible gastroenteritis virus and human severe acute respiratory syndrome coronavirus.the discovery and development of new, highly potent anti-coronavirus agents and effective approaches for controlling the potential emergence of epidemic coronaviruses still remains an important mission. here, we identified tylophorine compounds, including naturally occurring and synthetic phenanthroindolizidines and phenanthroquinolizidines, as potent in vitro inhibitors of enteropathogenic coronavirus transmissible gastroenteritis virus (tgev). the potent compounds showed 50% maximal effective ...201020727913
the american society for virology--29th annual meeting.the american society for virology 29th annual meeting, held in bozeman, mt, usa, included topics covering new vaccine technologies, delivery methods and treatments in the field of virology. this conference report highlights selected presentations on human norovirus (hunov), sars coronavirus and rift valley fever virus vaccine technologies; programmed cell death-1 (pd1) blockade and hyperacute alpha-gal platform technology methods; aerosol vaccination delivery; novel technologies to produce influ ...201020799142
sars-coronavirus protein 6 conformations required to impede protein import into the nucleus.the severe acute respiratory syndrome coronavirus (sars-cov) genome encodes eight accessory proteins. accessory protein 6 is a 63-residue amphipathic peptide that accelerates coronavirus infection kinetics in cell culture and in mice. protein 6 is minimally bifunctional, with an n-terminal lipophilic part implicated in accelerating viral growth and a c-terminal hydrophilic part interfering with general protein import into the nucleus. this interference with nuclear import requires interaction be ...201020800627
update on sars research and other possibly zoonotic coronaviruses.the global outbreak of severe acute respiratory syndrome (sars) in 2003 led to an intense and effective global response that stopped the spread of the disease by july 2003. there was also an intensive and very productive research effort to identify the aetiological agent, characterise the clinical and epidemiological features of the disease, understand the pathogenesis of the disease and the molecular biology of the virus, and design antiviral drugs and vaccines to treat and prevent the disease. ...201020801001
generating stable chinese hamster ovary cell clones to produce a truncated sars-cov spike protein for vaccine development.the spike (s) protein of the severe acute respiratory syndrome coronavirus (sars-cov) is important for vaccine development. s(tr2) (an 88 kda truncated sars-cov tw1 s protein carrying the s fragments s-74-253, s-294-739, and s-1129-1255) is capable of expressing a major form of glycoprotein as endo h-sensitive (∼115 kda) in cho cells. to establish stable expressing cell clones, we transfected cho/dhfr-cells with the amplifiable vectors isid (ires-driven dhfr) and isiz (sv40-driven dhfr) to selec ...201020809484
generating stable chinese hamster ovary cell clones to produce a truncated sars-cov spike protein for vaccine development.the spike (s) protein of the severe acute respiratory syndrome coronavirus (sars-cov) is important for vaccine development. s(tr2) (an 88 kda truncated sars-cov tw1 s protein carrying the s fragments s-74-253, s-294-739, and s-1129-1255) is capable of expressing a major form of glycoprotein as endo h-sensitive (∼115 kda) in cho cells. to establish stable expressing cell clones, we transfected cho/dhfr-cells with the amplifiable vectors isid (ires-driven dhfr) and isiz (sv40-driven dhfr) to selec ...201020809484
vigor, an annotation program for small viral genomes.the decrease in cost for sequencing and improvement in technologies has made it easier and more common for the re-sequencing of large genomes as well as parallel sequencing of small genomes. it is possible to completely sequence a small genome within days and this increases the number of publicly available genomes. among the types of genomes being rapidly sequenced are those of microbial and viral genomes responsible for infectious diseases. however, accurate gene prediction is a challenge that ...201020822531
use of a multiplex pcr/rt-pcr approach to assess the viral causes of influenza-like illnesses in cambodia during three consecutive dry seasons.acute respiratory infections are a major cause of mortality and morbidity worldwide. using multiplex pcr/rt-pcr methods for the detection of 18 respiratory viruses, the circulation of those viruses during 3 consecutive dry seasons in cambodia was described. among 234 patients who presented with influenza-like illness, 35.5% were positive for at least one virus. rhinoviruses (43.4%), parainfluenza (31.3%) viruses and coronaviruses (21.7%) were the most frequently detected viruses. influenza a vir ...201020827775
the membrane protein of severe acute respiratory syndrome coronavirus acts as a dominant immunogen revealed by a clustering region of novel functionally and structurally defined cytotoxic t-lymphocyte epitopes.severe acute respiratory syndrome coronavirus (sars-cov), which emerged with highly contagious and life-threatening characteristics in 2002, remains a potential risk for future outbreaks. membrane (m) and envelope (e) proteins are major structural proteins of the sars-cov. the m protein has been determined as a protective antigen in humoral responses. however, its potential roles in stimulating cellular immunity remain elusive.201020831383
[consecutive five-year follow-up analysis of specific igg antibody of 22 cases of sars patients after recovery].to study igg antibody persistence and temporal change in sars coronavirus (sars-cov) infected patients, 22 patients recovered from sars in beijing were recruited and followed-up from 2004 to 2008, serum samples from patients were collected every year. we checked and analyzed the sars-cov igg antibody (ab) for five consecutive years using the commercial elisa test kit. the results showed that: all of the serum were sars-igg antibody-positive the first year after recovery, the titer of most serum ...201020836383
[the research and application of inhibitory effect of rna-based strategies on sars]. 201020836389
novel immunodominant peptide presentation strategy: a featured hla-a*2402-restricted cytotoxic t-lymphocyte epitope stabilized by intrachain hydrogen bonds from severe acute respiratory syndrome coronavirus nucleocapsid protein.antigenic peptides recognized by virus-specific cytotoxic t lymphocytes (ctls) are presented by major histocompatibility complex (mhc; or human leukocyte antigen [hla] in humans) molecules, and the peptide selection and presentation strategy of the host has been studied to guide our understanding of cellular immunity and vaccine development. here, a severe acute respiratory syndrome coronavirus (sars-cov) nucleocapsid (n) protein-derived ctl epitope, n1 (qfkdnvill), restricted by hla-a*2402 was ...201020844028
the sars coronavirus e protein interacts with pals1 and alters tight junction formation and epithelial morphogenesis.intercellular tight junctions define epithelial apicobasal polarity and form a physical fence which protects underlying tissues from pathogen invasions. pals1, a tight junction-associated protein, is a member of the crumbs3-pals1-patj polarity complex, which is crucial for the establishment and maintenance of epithelial polarity in mammals. here we report that the carboxy-terminal domain of the sars-cov e small envelope protein (e) binds to human pals1. using coimmunoprecipitation and pull-down ...201020861307
Refresh
firstprev
...21222324252627282930...
nextlast
Displaying items 2601 - 2700 of 3881