Publications
| Title | Abstract | Year Filter | PMID(sorted ascending) Filter |
|---|
| the refined structure of human rhinovirus 16 at 2.15 a resolution: implications for the viral life cycle. | rhinoviruses belong to the picornavirus family and are small, icosahedral, non-enveloped viruses containing one positive rna strand. human rhinovirus 16 (hrv16) belongs to the major receptor group of rhinoviruses, for which the cellular receptor is intercellular adhesion molecule-1 (icam-1). in many rhinoviruses, one of the viral coat proteins (vp1) contains a hydrophobic pocket which is occupied by a fatty acid-like molecule, or so-called 'pocket factor'. antiviral agents have been shown to bin ... | 1997 | 9083115 |
| the pentamer channel stiffening model for drug action on human rhinovirus hrv-1a. | development of effective drugs against the rhinovirus (hrv) responsible for the common cold remains a challenge because there are over 100 serotypes. this process could be significantly aided by an understanding of the atomistic mechanism by which such drugs work. we suggest that the most effective drugs against hrv-1a act by stiffening the pentamer channel of the viral coat through which the rna is released, preventing the steps leading to uncoating. using molecular dynamics methods we tested t ... | 1997 | 9122218 |
| translation and replication properties of the human rhinovirus genome in vivo and in vitro. | the poor translation efficiency of genome-length human rhinovirus rna in vitro using hela cell extract-supplemented rabbit reticulocyte lysate has hampered the study of rhinovirus ires-mediated translation and polyprotein synthesis in a cell-free system. in contrast, the efficient in vitro translation characteristics of poliovirus rnas have ultimately allowed the programming of cell-free coupled translation/replication extracts which are able to produce infectious poliovirus particles in vitro. ... | 1997 | 9123881 |
| cleavage specificity of human rhinovirus-2 2a protease for peptide substrates. | substrate requirements of the human rhinovirus serotype-2 2a protease have been examined using synthetic peptides. a chromogenic peptide with a sequence of trpiitta-p-nitroanilide was found to be cleaved efficiently by the 2a protease with an apparent km value of 95 microm, which allowed the protease activity to be monitored and measured continuously using a spectrophotometer. competition cleavage assays reveal this peptide was cleaved over 10-fold more efficiently than the 16-mer peptide derive ... | 1997 | 9207196 |
| [rhinovirus infection and expression of adhesion molecules in human tracheal epithelium]. | rhinovirus infection has attracted attention because it can lead to acute exacerbations of chronic inflammatory airway diseases such as bronchial asthma and chronic bronchitis. we established a culture system and inoculated human rhinovirus to human tracheal epithelial cells, and found that infection was augmented by up-regulation of intercellular adhesion molecule-1, which is the receptor for this virus. we also found that human airway epithelial cells infected with rhinovirus were susceptible ... | 1996 | 9216200 |
| internalization of human rhinovirus 14 into hela and icam-1-transfected bhk cells. | virus adsorption and uptake of human rhinovirus 14 (hrv14) were studied with hela cells and baby hamster kidney (bhk) cells which were transfected with the hrv14 receptor intercellular adhesion molecule-1 (icam-1). transmission electron microscopy of hela cells revealed that hrv14 was internalized via clathrin-coated pits and -coated vesicles. a minority of virus particles also used uncoated vesicles for entry. the internalization showed the characteristics of receptor-mediated endocytosis. pres ... | 1997 | 9255760 |
| mutational analyses support a model for the hrv2 2a proteinase. | the proteinase 2a of human rhinovirus 2 is a cysteine proteinase which contains a tightly bound zn ion thought to be required for structural integrity. a three-dimensional model for human rhinovirus type 2 proteinase 2a (hrv2 2a) was established using sequence alignments with small trypsin-like ser-proteinases and, for certain regions, elastase. the model was tested by expressing selected proteinase 2a mutants in bacteria and examining the effect on both intramolecular ("cis") and intermolecular ... | 1997 | 9268151 |
| characterization of the t cell response to human rhinovirus in children: implications for understanding the immunopathology of the common cold. | human rhinovirus (hrv) is a frequent respiratory pathogen, responsible for a large proportion of cases of the "common cold" and linked to acute asthma, especially in children. t cell responses to hrv and their contribution to hrv-associated pathology were investigated. t cells were obtained from tonsils removed from children at routine tonsillectomy. proliferative and cytokine responses were measured after in vitro restimulation with purified hrv preparations of both major and minor serotypes. m ... | 1997 | 9291326 |
| expression and purification of recombinant rhinovirus 14 3cd proteinase and its comparison to the 3c proteinase. | human rhinovirus (hrv) is a positive-stranded rna virus with an open reading frame that encodes for a single polyprotein of about 3000 amino acids. the hrv polyprotein is proteolytically processed; eight of nine cleavages are catalyzed by the 3c and/or the 3cd proteinases. we have expressed and purified recombinant hrv14 3c and 3cd proteinases and investigated their substrate selectivity and inhibitor sensitivity. expressed 3cd proteinase had the p1/p1' residues of the 3c/3d cleavage site mutate ... | 1997 | 9328292 |
| a continuous colorimetric assay for rhinovirus-14 3c protease using peptide p-nitroanilides as substrates. | human rhinovirus encoded 3c protease is an attractive target for antiviral drug development. however, lack of a convenient and selective assay for 3c protease has been a hindrance in characterization of this enzyme and evaluation of a large number of potential inhibitors. in the present study we describe development of a simple, continuous colorimetric assay for this enzyme using peptide p-nitroanilides (pna) as substrates. several peptides mimicking the native 3c cleavage site of hrv-14 polypro ... | 1997 | 9344409 |
| intact eukaryotic initiation factor 4g is required for hepatitis a virus internal initiation of translation. | the requirements for optimal activity of the hepatitis a virus (hav) internal ribosome entry segment (ires) differ substantially from those of other picornavirus ireses. one such difference is that, to date, the hav ires is the only one whose efficiency is severely inhibited in the presence of the picornaviral 2a proteinase. here we describe experiments designed to dissect the mechanism of proteinase-mediated inhibition of hav translation. using dicistronic mrnas translated in vitro, we show tha ... | 1997 | 9344915 |
| frequency and natural history of rhinovirus infections in adults during autumn. | human rhinovirus (hrv) accounts for a significant portion of common-cold illness, with the peak incidence being in the early fall. three hundred forty-six adults who had self-diagnosed colds of 48 h or less were enrolled in a study during september and october 1994 to determine the frequency and clinical course of hrv infections. nasal wash specimens for viral culture and reverse transcription-pcr (rt-pcr) for hrv rna and human coronavirus oc43 and 229e rna detection were collected on enrollment ... | 1997 | 9350748 |
| zinc-induced suppression of inflammation in the respiratory tract, caused by infection with human rhinovirus and other irritants. | free ionic zinc (zn2+) in saliva shortens duration and severity of common cold (cc) symptoms. it is proposed that zn2+ complexes with proteins of critical nerve endings and surface proteins of human rhinovirus (hrv) (a) interrupt nerve impulses and (b) block docking of hrv on intercellular adhesion molecule-1 (icam-1) on somatic cells, thereby interrupting hrv infection. since leukocyte function associated antigen-1 (lfa-1) binds leukocytes to cells through icam-1, initiating inflammation, zn2+ ... | 1997 | 9352505 |
| rhinovirus infection of primary cultures of human tracheal epithelium: role of icam-1 and il-1beta. | exacerbations of asthma are often associated with respiratory infection caused by rhinoviruses. to study the effects of rhinovirus infection on respiratory epithelium, a primary target for respiratory viruses, human rhinovirus (hrv)-2 and hrv-14 were infected to primary cultures of human tracheal epithelial cells. viral infection was confirmed by showing that viral titers of supernatants and lysates from infected cells increased with time and by polymerase chain reaction. hrv-2 and hrv-14 infect ... | 1997 | 9357849 |
| iris explorer software for radial-depth cueing reovirus particles and other macromolecular structures determined by cryoelectron microscopy and image reconstruction. | structures of biological macromolecules determined by transmission cryoelectron microscopy (cryo-tem) and three-dimensional image reconstruction are often displayed as surface-shaded representations with depth cueing along the viewed direction (z cueing). depth cueing to indicate distance from the center of virus particles (radial-depth cueing, or r cueing) has also been used. we have found that a style of r cueing in which color is applied in smooth or discontinuous gradients using the iris exp ... | 1997 | 9361260 |
| protein engineering to create biologically active peptides: recombinant human rhinoviruses that display peptide sequences. | this paper describes the use of human rhinovirus to display peptides corresponding to biologically active sequences. while this system can be used to reconstruct essentially any biologically active sequence for which there is a corresponding ligand that can be used for its selection, we have focused on using this system to display immunogens from dangerous pathogens as a means to develop vaccines. five mutagenesis approaches are illustrated as ways to generate functionally active moieties. the m ... | 1997 | 9382744 |
| antirhino/enteroviral vinylacetylene benzimidazoles: a study of their activity and oral plasma levels in mice. | in an effort to find an orally bioavailable antiviral for the treatment of rhino/enteroviral infections, a series of vinylacetylene benzimidazoles (11a-o, 12, and 18a) was made. initial studies of this class of antivirals showed that fluorine substitution on the left-hand phenyl ring in combination with the vinylacetylene moiety gave the requisite mix of physical properties to achieve good in vitro antiviral activity as well as respectable oral bioavailability in rhesus monkeys. to ascertain the ... | 1997 | 9397174 |
| human rhinovirus type 14:human immunodeficiency virus type 1 (hiv-1) v3 loop chimeras from a combinatorial library induce potent neutralizing antibody responses against hiv-1. | in an effort to develop a useful aids vaccine or vaccine component, we have generated a combinatorial library of chimeric viruses in which the sequence igpgrafyttkn from the v3 loop of the mn strain of human immunodeficiency virus type 1 (hiv-1) is displayed in many conformations on the surface of human rhinovirus 14 (hrv14). the v3 loop sequence was inserted into a naturally immunogenic site of the cold-causing hrv14, bridged by linkers consisting of zero to three randomized amino acids on each ... | 1998 | 9420270 |
| nitric oxide inhibits rhinovirus-induced cytokine production and viral replication in a human respiratory epithelial cell line. | to better understand the early biochemical events that occur in human rhinovirus (hrv) infections, we examined the kinetics and mechanisms of interleukin-8 (il-8) and il-6 production from infected epithelial cells. several hrv strains caused il-8 and il-6 production, but hrv-16 induced maximal il-8 and il-6 mrna expression and protein production more rapidly than did hrv-14, despite similar rates of replication of the two viral strains. viral induction of cytokine mrna does not require new prote ... | 1998 | 9444985 |
| win 52035-dependent human rhinovirus 16: assembly deficiency caused by mutations near the canyon surface. | three drug-dependent mutants of human rhinovirus 16 (hrv16) were characterized by sequence analyses of spontaneous mutant isolates and were genetically reconstructed from a parental cdna plasmid. these mutants formed plaques in the presence but not in the absence of the selecting antiviral drug, win 52035, which binds to the capsid of wild-type virus and inhibits its attachment to the host cell. the drug-dependent phenotype of each mutant was caused by a single amino acid substitution in the vp1 ... | 1998 | 9445020 |
| enzymatic characterization of refolded human rhinovirus type 14 2a protease expressed in escherichia coli. | reported here is the production of recombinant human rhinovirus 14 (hrv14) 2a protease from bacterial cells transformed with a heat-inducible plasmid containing the hrv14 2a cdna sequence. overexpressed 2a protein partitioned into the inclusion bodies was solubilized in urea and then refolded in the presence of zn2+ transition metals were required for the restoration of 2a protease activity as a structural component, but appeared to be inhibitory if added exogenously once the enzyme was refolded ... | 1998 | 9445078 |
| energetics of quasiequivalence: computational analysis of protein-protein interactions in icosahedral viruses. | quaternary structure polymorphism found in quasiequivalent virus capsids provides a static framework for studying the dynamics of protein interactions. the same protein subunits are found in different structural environments within these particles, and in some cases, the molecular switching required for the polymorphic quaternary interactions is obvious from high-resolution crystallographic studies. employing atomic resolution structures, molecular mechanics, and continuum electrostatic methods, ... | 1998 | 9449355 |
| modeling rna-ligand interactions: the rev-binding element rna-aminoglycoside complex. | an approach to the modeling of ligand-rna complexes has been developed by combining three-dimensional structure-activity relationship (3d-sar) computations with a docking protocol. the ability of 3d-sar to predict bound conformations of flexible ligands was first assessed by attempting to reconstruct the known, bound conformations of phenyloxazolines complexed with human rhinovirus 14 (hrv14) rna. subsequently, the same 3d-sar analysis was applied to the identification of bound conformations of ... | 1998 | 9457241 |
| markers of airway inflammation in preschool wheezers. | airways inflammation markers may help in predicting prognosis, in diagnosis and in monitoring respiratory diseases. inflammation markers specific for certain cells may indicate the nature of the inflammatory processes, whilst others indicate stage and intensity. intercellular adhesion molecule 1 (icam-1) helps to establish contact between the antigen-presenting cell and t-lymphocytes. soluble serum icam-1 is increased in developing chronic lung disease of the newborn and atopic bronchial asthma. ... | 1997 | 9510666 |
| use of free-flow electrophoresis for the analysis of cellular uptake of picornaviruses. | free-flow electrophoresis is a powerful tool to separate subcellular vesicles such as early and late endosomes from plasma membranes. using this technique, the intracellular distribution of poliovirus type 2 sabin (pv2) and its derived subviral particles was analyzed upon infection of hela cells. comparison of various infection conditions showed that maximally 30% of total cell associated pv2 was found in endosomal compartments with the remainder being associated with plasma membrane fractions; ... | 1997 | 9527481 |
| structure of a neutralizing antibody bound monovalently to human rhinovirus 2. | the structure of a complex between human rhinovirus 2 (hrv2) and the fab fragment of neutralizing monoclonal antibody (mab) 3b10 has been determined to 25-a resolution by cryoelectron microscopy and three-dimensional reconstruction techniques. the footprint of 3b10 on hrv2 is very similar to that of neutralizing mab 8f5, which binds bivalently across the icosahedral twofold axis. however, the 3b10 fab fragment (fab-3b10) is bound in an orientation, inclined at approximately 45 degrees to the sur ... | 1998 | 9557730 |
| dual inhibition of human rhinovirus 2a and 3c proteases by homophthalimides. | the 2a and 3c proteases encoded by human rhinoviruses (hrvs) are attractive targets for antiviral drug development due to their important roles in viral replication. homophthalimides were originally identified as inhibitors of rhinovirus 3c protease through our screening effort. previous studies have indicated that the antiviral activity of certain homophthalimides exceeded their in vitro inhibitory activity against the viral 3c protease, suggesting that an additional mechanism might be involved ... | 1998 | 9559808 |
| eosinophils bind rhinovirus and activate virus-specific t cells. | episodes of virus-induced exacerbations of asthma are accompanied by increased eosinophils (eos) in respiratory secretions and evidence of eos degranulation. although rhinoviruses (rv) are the viruses most often implicated in exacerbations of asthma in both children and adults, little is known about the immune response to this group of viruses and, in particular, eos-rv interactions. to define such interactions, we incubated human rhinovirus type 16 (rv16), a serotype using icam-1 as a receptor, ... | 1998 | 9570544 |
| antibody-mediated neutralization of human rhinovirus 14 explored by means of cryoelectron microscopy and x-ray crystallography of virus-fab complexes. | the structures of three different human rhinovirus 14 (hrv14)-fab complexes have been explored with x-ray crystallography and cryoelectron microscopy procedures. all three antibodies bind to the nim-ia site of hrv14, which is the beta-b-beta-c loop of the viral capsid protein vp1. two antibodies, fab17-ia (fab17) and fab12-ia (fab12), bind bivalently to the virion surface and strongly neutralize viral infectivity whereas fab1-ia (fab1) strongly aggregates and weakly neutralizes virions. the stru ... | 1998 | 9573224 |
| antiviral agent blocks breathing of the common cold virus. | a dynamic capsid is critical to the events that shape the viral life cycle; events such as cell attachment, cell entry, and nucleic acid release demand a highly mobile viral surface. protein mass mapping of the common cold virus, human rhinovirus 14 (hrv14), revealed both viral structural dynamics and the inhibition of such dynamics with an antiviral agent, win 52084. viral capsid digestion fragments resulting from proteolytic time-course experiments provided structural information in good agree ... | 1998 | 9618488 |
| development and application of a new method for amplification and detection of human rhinovirus rna. | a method based on nucleic acid sequence based amplification (nasba) was developed for detection of rhinovirus rna. appropriate collection and storage conditions for maintenance of rhinovirus rna integrity in clinical samples was determined. two silica-based extraction methods were evaluated for preparation of rna from virus isolates and clinical samples. primers and probes were selected from the non-translated region at the 5' end and from vp4 of sequenced rhinoviruses. amplified products were d ... | 1998 | 9626953 |
| a biological model to explain the association between human rhinovirus respiratory infections and bronchial asthma. | human rhinoviruses (hrvs) are a frequent cause or upper respiratory tract infections in children and adults, and can exacerbate existing pulmonary disease. the major group of hrv attach to the receptor intercellular adhesion molecule (icam)-1, which is expressed on many cell types including epithelial cells. to study the influence of biological mediators on icam-1 expression, and consequently hrv attachment and infection, we have established an in vitro model system to evaluate the effects or pr ... | 1998 | 9632914 |
| viruses and asthmatic syndromes. | viruses are recognized to be the major cause of respiratory infections. clinical and experimental evidence also supports an important role for viruses in the pathogenesis of lower airway disease and asthma exacerbation. in prospective epidemiological studies, 80% of asthma exacerbations in school-aged children and half of all asthma exacerbations in adults have been associated with viral upper respiratory infections. human rhinovirus (hrv) has been implicated as the principal virus associated wi ... | 1998 | 9632915 |
| direct cleavage of elf4g by poliovirus 2a protease is inefficient in vitro. | previously, the purified recombinant 2a proteases (2apro) of coxsackievirus b4 (cvb4) and human rhinovirus type 2 (hrv2) were shown to cleave synthetic peptides derived from human or rabbit elf4g as well as elf4g protein purified from rabbit reticulocytes. these results were in contrast to previous evidence which supported the view that elf4g cleavage activity in poliovirus-infected hela cells required a cellular factor(s) activated by poliovirus (pv) 2apro. in the present study, recombinant pv ... | 1998 | 9636363 |
| accomplishments and challenges in picornavirology as observed by a medical doctor. | the family of picornaviridae has been studied extensively: the structure of the virion and its replication strategy are known in molecular detail. nevertheless, infections with the multitude of enteroviruses still cause widespread epidemics, serious disease and a diversity of clinical syndromes ranging from central nervous system involvement to light febrile illness. infections with more than 100 human rhinovirus types are an important economic factor. | 1998 | 9645987 |
| molecular diagnosis of human rhinovirus infections: comparison with virus isolation. | to compare the sensitivity and specificity of rt-pcr with that of virus isolation in the detection of human rhinoviruses, we tested nasopharyngeal aspirates from 200 patients on the 1st and 7th days after the onset of the common cold. an assay utilizing a short amplicon in the conserved 5' noncoding region was found highly sensitive. of 192 positive samples altogether, 65 were found positive by rt-pcr only, 6 were positive by isolation exclusively, and 121 gave positive results in both tests. | 1998 | 9650967 |
| synthesis and evaluation of peptidyl michael acceptors that inactivate human rhinovirus 3c protease and inhibit virus replication. | human rhinovirus, the chief cause of the common cold, contains a positive-sense strand of rna which is translated into a large polyprotein in infected cells. cleavage of the latter to produce the mature viral proteins required for replication is catalyzed in large part by a virally encoded cysteine proteinase (3cpro) which is highly selective for -q approximately gp- cleavage sites. we synthesized peptidyl derivatives of vinylogous glutamine or methionine sulfone esters (e.g., boc-val-leu-phe-vg ... | 1998 | 9651162 |
| effects of rhinovirus infection on hydrogen peroxide- induced alterations of barrier function in the cultured human tracheal epithelium. | to investigate whether rhinovirus infection impairs epithelial barrier functions, human rhinovirus 14 (hrv-14) was infected to primary cultures of human tracheal epithelial cells and experiments were performed on day 2 after hrv-14 infection. hydrogen peroxide (h2o2; 3 x 10(-)4 m) increased electrical conductance (g) across the epithelial cell sheet measured with ussing's chamber methods. exposure of the epithelial cells to hrv-14 had no effect on h2o2-induced increases in g and [3h]mannitol flu ... | 1998 | 9655736 |
| tripeptide aldehyde inhibitors of human rhinovirus 3c protease: design, synthesis, biological evaluation, and cocrystal structure solution of p1 glutamine isosteric replacements. | the investigation of tripeptide aldehydes as reversible covalent inhibitors of human rhinovirus (hrv) 3c protease (3cp) is reported. molecular models based on the apo crystal structure of hrv-14 3cp and other trypsin-like serine proteases were constructed to approximate the binding of peptide substrates, generate transition state models of p1-p1' amide cleavage, and propose novel tripeptide aldehydes. glutaminal derivatives have limitations since they exist predominantly in the cyclic hemiaminal ... | 1998 | 9667969 |
| structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3c protease inhibitors. 1. michael acceptor structure-activity studies. | the structure-based design, chemical synthesis, and biological evaluation of peptide-derived human rhinovirus (hrv) 3c protease (3cp) inhibitors are described. these compounds incorporate various michael acceptor moieties and are shown to irreversibly bind to hrv serotype 14 3cp with inhibition activities (kobs/[i]) ranging from 100 to 600 000 m-1 s-1. these inhibitors are also shown to exhibit antiviral activity when tested against hrv-14-infected h1-hela cells with ec50's approaching 0.50 micr ... | 1998 | 9667970 |
| structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3c protease inhibitors. 2. peptide structure-activity studies. | the structure-based design, chemical synthesis, and biological evaluation of various peptide-derived human rhinovirus (hrv) 3c protease (3cp) inhibitors are described. these compounds are comprised of an ethyl propenoate michael acceptor moiety and a tripeptidyl binding determinant. the systematic modification of each amino acid residue present in the binding determinant as well as the n-terminal functionality is described. such modifications are shown to provide irreversible hrv-14 3cp inhibito ... | 1998 | 9667971 |
| identification of viral mutants by mass spectrometry. | a method to identify mutations of virus proteins by using protein mass mapping is described. comparative mass mapping was applied to a structural protein of the human rhinovirus cys1199 --> tyr mutant and to genetically engineered mutants of tobacco mosaic virus. the information generated from this approach can rapidly identify the peptide or protein containing the mutation and, in cases when nucleic acid sequencing is required, significantly narrows the region of the genome that must be sequenc ... | 1998 | 9671723 |
| development of in vitro peptide substrates for human rhinovirus-14 2a protease. | purified 2a protease from human rhinovirus serotype-14 (hrv14) was unable to efficiently cleave a 16-mer peptide representing its authentic cis-cleavage site on the viral polyprotein, implying that in vivo cis cleavage by this enzyme might be very different from its in vitro trans activity. presence of a serine at position p2 and a leucine at p2' in the 16-mer peptide was found to be responsible for the low peptide cleavage efficiency. to search for an efficient peptide substrate for hrv14 2a, s ... | 1998 | 9681985 |
| detection of rhinovirus, respiratory syncytial virus, and coronavirus infections in acute otitis media by reverse transcriptase polymerase chain reaction. | to determine the frequencies of human rhinovirus (hrv), respiratory syncytial virus (rsv), and coronavirus (hcv) infection in children with acute otitis media (aom). | 1998 | 9685428 |
| the clathrin endocytic pathway in viral infection. | how important is the clathrin-dependent endocytic pathway for entry of viruses into host cells? while it is widely accepted that semliki forest virus (sfv), an enveloped virus, requires this pathway there are conflicting data concerning the closely related sindbis virus, as well as varying results with picornaviruses such as human rhinovirus 14 (hrv 14) and poliovirus. we have examined the entry mode of sfv, sindbis virus, hrv 14 and poliovirus using a method that identifies single infected cell ... | 1998 | 9707418 |
| trans-encapsidation of a poliovirus replicon by different picornavirus capsid proteins. | a trans-encapsidation assay was established to study the specificity of picornavirus rna encapsidation. a poliovirus replicon with the luciferase gene replacing the capsid protein-coding region was coexpressed in transfected hela cells with capsid proteins from homologous or heterologous virus. successful trans-encapsidation resulted in assembly and production of virions whose replication, upon subsequent infection of hela cells, was accompanied by expression of luciferase activity. the amount o ... | 1998 | 9733835 |
| polymerase chain reaction-based detection of rhinovirus, respiratory syncytial virus, and coronavirus in otitis media with effusion. | to study the association of human rhinovirus (hrv), respiratory syncytial virus (rsv), and human coronavirus infections in children aged 6 months to 12 years with otitis media with effusion (ome). to determine how long hrv rna can be detected after hrv infection. | 1998 | 9738723 |
| th2 cytokines exert a dominant influence on epithelial cell expression of the major group human rhinovirus receptor, icam-1. | intercellular adhesion molecule (icam)-1 is a cell receptor important in both human rhinovirus (hrv) attachment and immune effector cell mobilization. the level of expression of icam-1 by epithelial cells (ec) therefore plays a crucial role in the intricate biological phenomena underlying viral binding, host infection and consequent inflammatory events. as t-helper (th)2 lymphocytes predominate within the asthmatic airway, the influence was evaluated of th2-associated mediators in the modulation ... | 1998 | 9762790 |
| protease inhibitors as antiviral agents. | currently, there are a number of approved antiviral agents for use in the treatment of viral infections. however, many instances exist in which the use of a second antiviral agent would be beneficial because it would allow the option of either an alternative or a combination therapeutic approach. accordingly, virus-encoded proteases have emerged as new targets for antiviral intervention. molecular studies have indicated that viral proteases play a critical role in the life cycle of many viruses ... | 1998 | 9767059 |
| flexs: a method for fast flexible ligand superposition. | if no structural information about a particular target protein is available, methods of rational drug design try to superimpose putative ligands with a given reference, e.g., an endogenous ligand. the goal of such structural alignments is, on the one hand, to approximate the binding geometry and, on the other hand, to provide a relative ranking of the ligands with respect to their similarity. an accurate superposition is the prerequisite of subsequent exploitation of ligand data by either 3d qsa ... | 1998 | 9804690 |
| determination of the affinity and kinetic constants for the interaction between the human virus echovirus 11 and its cellular receptor, cd55. | the biochemical properties of the molecular interactions mediating viral-cell recognition are poorly characterized. in this study, we use surface plasmon resonance to study the affinity and kinetics of the interaction of echovirus 11 with its cellular receptor decay-accelerating factor (cd55). as reported for interactions between cell-cell recognition molecules, the interaction has a low affinity (kd approximately 3.0 microm) as a result of a very fast dissociation rate constant (kon approximate ... | 1998 | 9804811 |
| effect of bafilomycin a1 and nocodazole on endocytic transport in hela cells: implications for viral uncoating and infection. | bafilomycin a1 (baf), a specific inhibitor of vacuolar proton atpases, is commonly employed to demonstrate the requirement of low endosomal ph for viral uncoating. however, in certain cell types baf also affects the transport of endocytosed material from early to late endocytic compartments. to characterize the endocytic route in hela cells that are frequently used to study early events in viral infection, we used 35s-labeled human rhinovirus serotype 2 (hrv2) together with various fluid-phase m ... | 1998 | 9811698 |
| very-low-density lipoprotein receptor fragment shed from hela cells inhibits human rhinovirus infection. | the large family of human rhinoviruses, the main causative agents of the common cold, is divided into the major and the minor group based on receptor specificity. major group viruses attach to intercellular adhesion molecule 1 (icam-1), a member of the immunoglobulin superfamily, whereas minor group viruses use low-density lipoprotein receptors (ldlr) for cell entry. during early attempts aimed at isolating the minor group receptor, we discovered that a protein with virus binding activity was re ... | 1998 | 9811769 |
| soluble ldl minireceptors. minimal structure requirements for recognition of minor group human rhinovirus. | soluble human low density lipoprotein minireceptors with less than seven ligand binding repeats (as are present in the native membrane receptor) were expressed in sf9 insect cells with a hexa-his tag fused to the c terminus. the recombinant truncated proteins were affinity purified from the tissue culture supernatants by ni-nta column chromatography. minireceptors with more than two repeats bound to rabbit beta very low density lipoprotein and could thus be further purified by affinity chromatog ... | 1998 | 9837974 |
| the rhinovirus type 14 genome contains an internally located rna structure that is required for viral replication. | cis-acting rna signals are required for replication of positive-strand viruses such as the picornaviruses. although these generally have been mapped to the 5' and/or 3' termini of the viral genome, rnas derived from human rhinovirus type 14 are unable to replicate unless they contain an internal cis-acting replication element (cre) located within the genome segment encoding the capsid proteins. here, we show that the essential cre sequence is 83-96 nt in length and located between nt 2318-2413 o ... | 1998 | 9848654 |
| responses to human rhinovirus in cd45 t cell subsets isolated from tonsil. | isotypes of cd45 have been used extensively as markers of memory and naive populations of t cells in peripheral blood. in this study, t cells were isolated from human tonsil and their proliferative response against human rhinovirus was measured. unexpectedly, equivalent responses were found among the cd4+cd45ra+ and cd4+cd45ro+ populations of t cells. this response requires mhc class ii-positive antigen-presenting cells. the time course of the t cell response in vitro was that of a classical rec ... | 1998 | 9862374 |
| dual stem loops within the poliovirus internal ribosomal entry site control neurovirulence. | in the human central nervous system, susceptibility to poliovirus (pv) infection is largely confined to a specific subpopulation of neuronal cells. pv tropism is likely to be determined by cell-external components such as the pv receptor cd155, as well as cell-internal constraints such as the availability of a suitable microenvironment for virus propagation. we reported previously that the exchange of the cognate internal ribosomal entry site (ires) within the 5' nontranslated region of pv with ... | 1999 | 9882296 |
| 2-amino-3-substituted-6-[(e)-1-phenyl-2-(n-methylcarbamoyl)vinyl]imid azo[1,2-a]pyridines as a novel class of inhibitors of human rhinovirus: stereospecific synthesis and antiviral activity. | a series of 2-amino-3-substituted-6-[(e)-1-phenyl-2-(n-methylcarbamoyl)vinyl]+ ++imid azo[1,2-a]pyridines 1a-i, structurally related to enviroxime and its analogous benzimidazoles, was designed and prepared for testing as antirhinovirus agents. the imidazo ring in this class of compounds was constructed starting from the aminopyridine after tosylation and subsequent treatment with the appropriate acetamides. the key steps in the synthesis include the development and use of a new horner-emmons re ... | 1999 | 9888832 |
| inhibition of 3c protease from human rhinovirus strain 1b by peptidyl bromomethylketonehydrazides. | the gene coding for the 3c protease from human rhinovirus strain 1b was efficiently expressed in an escherichia coli strain which also overexpressed the rare argu trna. the protease was isolated from inclusion bodies, refolded, and exhibited a kcat/km = 3280 m-1 s-1 using an internally quenched peptidyl fluorogenic substrate. this continuous fluorogenic assay was used to measure the kinetics of 3c protease inhibition by several conventional peptidyl chloromethylketones as well as a novel series ... | 1999 | 9989947 |
| low temperature and pressure stability of picornaviruses: implications for virus uncoating. | the family picornaviridae includes several viruses of great economic and medical importance. poliovirus replicates in the human digestive tract, causing disease that may range in severity from a mild infection to a fatal paralysis. the human rhinovirus is the most important etiologic agent of the common cold in adults and children. foot-and-mouth disease virus (fmdv) causes one of the most economically important diseases in cattle. these viruses have in common a capsid structure composed of 60 c ... | 1999 | 10049311 |
| unr, a cellular cytoplasmic rna-binding protein with five cold-shock domains, is required for internal initiation of translation of human rhinovirus rna. | initiation of translation of the animal picornavirus rnas occurs via a mechanism of direct ribosome entry, which requires a segment of the 5' utr of the rna, known as the internal ribosome entry site (ires). in addition, translation of the enterovirus and rhinovirus (hrv) subgroups requires cellular trans-acting factors that are absent from, or limiting in rabbit reticulocytes, but are more abundant in hela cell extracts. it has been shown previously that hela cells contain two separable activit ... | 1999 | 10049359 |
| eukaryotic initiation factor 4gii (eif4gii), but not eif4gi, cleavage correlates with inhibition of host cell protein synthesis after human rhinovirus infection. | for many members of the picornaviridae family, infection of cells results in a shutoff of host protein synthesis. for rhinoviruses and enteroviruses, the shutoff has been explained in part by the cleavage of eukaryotic initiation factor 4gi (eif4gi), a component of the cap-binding protein complex eif4f. the cleavage of eif4gi is mediated by the virus-specific proteinase 2apro and results in inhibition of cap-dependent, but not cap-independent, translation. the inhibition of host protein synthesi ... | 1999 | 10074204 |
| recombinant soluble low-density lipoprotein receptor fragment inhibits common cold infection. | a fragment of the human low-density lipoprotein receptor encompassing the seven ligand-binding repeats fused to a c-terminal oligo-his tag was expressed in sf9 insect cells. the melittin signal sequence encoded in the baculovirus vector led to secretion of the protein into the cell supernatant in a soluble form. the receptor fragment bound its natural ligand beta-migrating very-low-density lipoprotein and human rhinovirus serotype 2 in non-reducing ligand blots. infection of all minor group huma ... | 1998 | 10076805 |
| polypyrimidine-tract binding protein (ptb) is necessary, but not sufficient, for efficient internal initiation of translation of human rhinovirus-2 rna. | initiation of translation of the animal picornavirus rnas is via a mechanism of direct internal ribosome entry, which requires a substantial segment of the viral 5'-untranslated region, generally known as the ires (for "internal ribosome entry site"). because, however, translation of the rnas of members of the enterovirus, and more especially, the rhinovirus subgroups of the picornaviridae is restricted in the reticulocyte lysate system, but is greatly stimulated by the addition of hela cell ext ... | 1999 | 10094304 |
| design, synthesis, and evaluation of azapeptides as substrates and inhibitors for human rhinovirus 3c protease. | a series of azapeptides was prepared and assessed as inhibitors of the human rhinovirus 3c protease. boc-vlfaq-oph was a slow-turnover substrate that gave transient (ca. 1-2 h) inhibition as it underwent hydrolysis. boc-vlfag-oph gave very slow but essentially irreversible inhibition. | 1999 | 10098667 |
| structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3c protease inhibitors. 3. structure-activity studies of ketomethylene-containing peptidomimetics. | the structure-based design, chemical synthesis, and biological evaluation of various ketomethylene-containing human rhinovirus (hrv) 3c protease (3cp) inhibitors are described. these compounds are comprised of a peptidomimetic binding determinant and an ethyl propenoate michael acceptor moiety which forms an irreversible covalent adduct with the active site cysteine residue of the 3c enzyme. the ketomethylene-containing inhibitors typically display slightly reduced 3cp inhibition activity relati ... | 1999 | 10197964 |
| structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3c protease inhibitors. 4. incorporation of p1 lactam moieties as l-glutamine replacements. | the structure-based design, chemical synthesis, and biological evaluation of various human rhinovirus (hrv) 3c protease (3cp) inhibitors which incorporate p1 lactam moieties in lieu of an l-glutamine residue are described. these compounds are comprised of a tripeptidyl or peptidomimetic binding determinant and an ethyl propenoate michael acceptor moiety which forms an irreversible covalent adduct with the active site cysteine residue of the 3c enzyme. the p1-lactam-containing inhibitors display ... | 1999 | 10197965 |
| a disulfide-bound hiv-1 v3 loop sequence on the surface of human rhinovirus 14 induces neutralizing responses against hiv-1. | an immunogenic sequence from the v3 loop of the mn isolate of human immunodeficiency virus type 1 (hiv-1), his-ile-gly-pro-gly-arg-ala-phe, was transplanted onto a surface loop of the vp2 capsid protein of human rhinovirus 14. to optimize for virus viability and immunogenicity of the transplanted sequence, the hiv sequence was flanked by (1) a cysteine residue that could form a disulfide bond and (2) randomized amino acids (in either of two arrangements) to generate numerous presentations of the ... | 1999 | 10223339 |
| position-dependent processing of peptides presented on the surface of cowpea mosaic virus. | the plant virus cowpea mosaic virus (cpmv) has been developed as an epitope-presentation system. numerous epitopes have been expressed in the betab-betac loop of the cpmv small coat protein, all of which undergo a cleavage reaction between their two carboxy-terminal residues. although many peptides presented in this manner give an authentic immune response, this was not the case for the nim-1a epitope from human rhinovirus-14. crystallography revealed significant differences between the structur ... | 1999 | 10223342 |
| identification and characterization of human rhinovirus-14 3c protease deamidation isoform. | a purified recombinant human rhinovirus-14 3c protease preparation contained only approximately 50% active enzyme as titrated using specifically designed irreversible 3c protease inhibitors. analysis of the purified 3c protein by isoelectric focusing showed differently charged 3c isoforms that had isoelectric points (pi) of 8.3 (55%) and 9.0 (45%), with the latter one being consistent with the predicted pi of the human rhinovirus-14 3c protein. further analysis indicated that the pi 8.3 protein ... | 1999 | 10224078 |
| solid-phase synthesis of irreversible human rhinovirus 3c protease inhibitors. part 1: optimization of tripeptides incorporating n-terminal amides. | the optimization of a series of irreversible human rhinovirus (hrv) 3c protease (3cp) inhibitors is described. these inhibitors are comprised of an l-leu-l-phe-l-gln tripeptide containing an n-terminal amide moiety and a c-terminal ethyl propenoate michael acceptor. examination of approximately 500 compounds with varying n-terminal amides utilizing solid-phase synthesis and high-throughput assay techniques is described along with the solution phase preparation of several highly active molecules. ... | 1999 | 10353638 |
| analysis of common cold virus (human rhinovirus serotype 2) by capillary zone electrophoresis: the problem of peak identification. | different preparations of human rhinovirus serotype 2 (hrv2), a common cold virus, were analyzed by capillary zone electrophoresis (cze) in untreated fused-silica capillaries using borate buffer (100 mmol/l, ph 8.3) and sodium dodecyl sulfate (10 mmol/l) as additive to prevent wall adsorption. the electropherograms showed one major peak at 205- and 254-nm detection wavelengths. the identity of the peak as originating from native virus was confirmed by several indirect methods. heating to 56 degr ... | 1999 | 10361502 |
| protease inhibitors as potential antiviral agents for the treatment of picornaviral infections. | the picornavirus family contains several human pathogens including human rhinovirus (hrv) and hepatitis a virus (hav). in the case of hrvs, these small single-stranded positive-sense rna viruses translate their genetic information into a polyprotein precursor which is further processed mainly by two viral proteases designated 2a and 3c. the 2a protease (2apro) makes the first cleavage between the structural and non-structural proteins, while 3c protease (3cpro) catalyzes most of the remaining in ... | 1999 | 10396129 |
| crystallization and preliminary x-ray analysis of human rhinovirus serotype 2 (hrv2). | human rhinoviruses, the major cause of mild recurrent infections of the upper respiratory tract, are small icosahedral particles. over 100 different serotypes have been identified. the majority (91 serotypes) use intercellular adhesion molecule 1 as the cell-attachment site; ten serotypes (the minor group) bind to members of the low-density lipoprotein receptor. three different crystal forms of the minor-group human rhinovirus serotype 2 (hrv2) were obtained by the hanging-drop vapour-diffusion ... | 1999 | 10417415 |
| enatioseparation and anti-rhinovirus activity of 3-benzylchroman-4-ones. | in a series of homo-isoflavonoids, chloro-substituted rac-3-benzylchroman-4-ones (3 d-f) showed an antiviral in vitro activity against selected picornaviruses. in order to study the anti-rhinovirus activity of each stereoisomer, racemic mixtures of 3 d and 3 e were successfully resolved by high-performance liquid chromatography, using a whelk-o 1 column as chiral stationary phase. the cd spectra confirm that the two eluates of each compound are enantiomers but do not allow the assignment of thei ... | 1999 | 10419285 |
| structure-based design of irreversible, tripeptidyl human rhinovirus 3c protease inhibitors containing n-methyl amino acids. | tripeptide-derived molecules incorporating n-methyl amino acid residues and c-terminal michael acceptor moieties were evaluated as irreversible inhibitors of the cysteine-containing human rhinovirus 3c protease (3cp). such compounds displayed good 3cp inhibition activity (k(obs)/[i] up to 610,000 m(-1) s(-1)) and potent in vitro antiviral properties (ec50 approaching 0.03 microm) when tested against hrv serotype-14. | 1999 | 10465543 |
| structure-assisted design of mechanism-based irreversible inhibitors of human rhinovirus 3c protease with potent antiviral activity against multiple rhinovirus serotypes. | human rhinoviruses, the most important etiologic agents of the common cold, are messenger-active single-stranded monocistronic rna viruses that have evolved a highly complex cascade of proteolytic processing events to control viral gene expression and replication. most maturation cleavages within the precursor polyprotein are mediated by rhinovirus 3c protease (or its immediate precursor, 3cd), a cysteine protease with a trypsin-like polypeptide fold. high-resolution crystal structures of the en ... | 1999 | 10500114 |
| a coding rna sequence acts as a replication signal in cardioviruses. | theiler's virus and mengo virus are representatives of the cardiovirus genus within the picornavirus family. their genome is an 8-kilobase long positive strand rna molecule. this rna molecule plays three roles in infected cells: it serves as a messenger rna, acts as a template for genome replication, and is encapsidated to form progeny virions. we observed that a cis-acting signal required for replication of theiler's virus was contained within a 130-nt stretch of the region encoding the capsid ... | 1999 | 10500216 |
| expression of a recombinant form of the v antigen of yersinia pestis, using three different expression systems. | yersinia pestis, the causative organism of plague, produces v antigen (lcrv), a bifunctional protein with regulatory and virulence roles that has been shown to be highly protective against a plague challenge. a combined sub-unit vaccine, comprising recombinant v and fraction 1 antigens is currently being developed. we report here the expression and purification of recombinant v antigen (rv) using three different expression systems: the n-terminal gst fusion pgex-5x-2 and pgex-6p-2 systems from p ... | 1999 | 10501245 |
| in vitro antiviral activity of ag7088, a potent inhibitor of human rhinovirus 3c protease. | ag7088 is a potent, irreversible inhibitor of human rhinovirus (hrv) 3c protease (inactivation rate constant (k(obs)/[i]) = 1,470,000 +/- 440,000 m(-1) s(-1) for hrv 14) that was discovered by protein structure-based drug design methodologies. in h1-hela and mrc-5 cell protection assays, ag7088 inhibited the replication of all hrv serotypes (48 of 48) tested with a mean 50% effective concentration (ec(50)) of 0.023 microm (range, 0.003 to 0.081 microm) and a mean ec(90) of 0.082 microm (range, 0 ... | 1999 | 10508022 |
| the structure of the 2a proteinase from a common cold virus: a proteinase responsible for the shut-off of host-cell protein synthesis. | the crystal structure of the 2a proteinase from human rhinovirus serotype 2 (hrv2-2a(pro)) has been solved to 1.95 a resolution. the structure has an unusual, although chymotrypsin-related, fold comprising a unique four-stranded beta sheet as the n-terminal domain and a six-stranded beta barrel as the c-terminal domain. a tightly bound zinc ion, essential for the stability of hrv2-2a(pro), is tetrahedrally coordinated by three cysteine sulfurs and one histidine nitrogen. the active site consists ... | 1999 | 10523291 |
| separation and biospecific identification of subviral particles of human rhinovirus serotype 2 by capillary zone electrophoresis. | during infection, human rhinoviruses undergo structural rearrangements of their capsid proteins from d-antigenic native virus (sedimenting at 150s upon sucrose density gradient centrifugation) to c-antigenic a-particles (sedimenting at 135s) and b-particles (sedimenting at 80s); the latter remain after release of the viral genomic rna into the cytosol. subviral particles with very similar properties can also be produced in vitro upon exposure to elevated temperatures or to low-ph buffers. this p ... | 1999 | 10546529 |
| similar interactions of the poliovirus and rhinovirus 3d polymerases with the 3' untranslated region of rhinovirus 14. | we showed previously that a human rhinovirus 14 (hrv14) 3' untranslated region (3' utr) on a poliovirus genome was able to replicate with nearly wild-type kinetics (j. b. rohll, d. h. moon, d. j. evans, and j. w. almond, j. virol 69:7835-7844, 1995). this enabled the hrv14 single 3' utr stem-loop structure to be studied in combination with a sensitive reporter system, poliovirus flc/rep, in which the capsid coding region is replaced by an in-frame chloramphemicol acetyltransferase (cat) gene. us ... | 1999 | 10559308 |
| structural studies of two rhinovirus serotypes complexed with fragments of their cellular receptor. | two human rhinovirus serotypes complexed with two- and five-domain soluble fragments of the cellular receptor, intercellular adhesion molecule-1, have been investigated by x-ray crystallographic analyses of the individual components and by cryo-electron microscopy of the complexes. the three-dimensional image reconstructions provide a molecular envelope within which the crystal structures of the viruses and the receptor fragments can be positioned with accuracy. the n-terminal domain of the rece ... | 1999 | 10562537 |
| molecular dynamics investigation of the effect of an antiviral compound on human rhinovirus. | the factors that influence the enhanced stability observed experimentally of human rhinovirus 14 (hrv14) upon binding a hydrophobic antiviral drug have been investigated by molecular dynamics. simulations centered about the hrv14 drug-binding pocket allow the reliable assessment of differences in capsid protein motions of hrv14 and drug-bound hrv14. we propose that the experimentally observed stabilization of the ligated virus arises from higher entropy, rather than enthalpy. time-averaged inter ... | 1999 | 10595531 |
| human rhinovirus hrv14 uncoats from early endosomes in the presence of bafilomycin. | determination of infectious progeny virus and in vivo labelling with [(35)s]methionine followed by immunoprecipitation demonstrates that the major receptor group human rhinovirus hrv14 is able to infect hela cells in the presence of the v-atpase inhibitor bafilomycin a1. however, host cell shut off is delayed and viral yield is decreased in the presence of the drug. uncoating can thus take place under conditions that prevent endosomal acidification indicating that it is catalysed by the viral re ... | 1999 | 10601662 |
| experimental common cold increases mucosal output of eotaxin in atopic individuals. | in view of recent observations demonstrating that rhinovirus infections are associated with increased local activity of eosinophils, we hypothesized that eotaxin, a selective eosinophil chemoattractant, may be involved in eosinophil recruitment/activation in common cold infections. | 1999 | 10604558 |
| differential utilization of poly(rc) binding protein 2 in translation directed by picornavirus ires elements. | the translation of picornavirus genomic rnas occurs by a cap-independent mechanism that requires the formation of specific ribonucleoprotein complexes involving host cell factors and highly structured regions of picornavirus 5' noncoding regions known as internal ribosome entry sites (ires). although a number of cellular proteins have been shown to be involved in picornavirus rna translation, the precise role of these factors in picornavirus internal ribosome entry is not understood. in this rep ... | 1999 | 10606268 |
| analysis of three structurally related antiviral compounds in complex with human rhinovirus 16. | rhinoviruses are a frequent cause of the common cold. a series of antirhinoviral compounds have been developed that bind into a hydrophobic pocket in the viral capsid, stabilizing the capsid and interfering with cell attachment. the structures of a variety of such compounds, complexed with rhinovirus serotypes 14, 16, 1a, and 3, previously have been examined. three chemically similar compounds, closely related to a drug that is undergoing phase iii clinical trials, were chosen to determine the s ... | 1999 | 10611281 |
| structure-based design of ketone-containing, tripeptidyl human rhinovirus 3c protease inhibitors. | tripeptide-derived molecules incorporating c-terminal ketone electrophiles were evaluated as reversible inhibitors of the cysteine-containing human rhinovirus 3c protease (3cp). an optimized example of such compounds displayed potent 3cp inhibition activity (k = 0.0045 microm) and in vitro antiviral properties (ec50=0.34 microm) when tested against hrv serotype-14. | 2000 | 10636240 |
| analysis of the c-myc ires; a potential role for cell-type specific trans-acting factors and the nuclear compartment. | the 5' utr of c -myc mrna contains an internal ribo-some entry segment (ires) and consequently, c -myc mrnas can be translated by the alternative mechanism of internal ribosome entry. however, there is also some evidence suggesting that c -myc mrna translation can occur via the conventional cap-dependent scanning mechanism. using both bicistronic and monocistronic mrnas containing the c- myc 5' utr, we demonstrate that both mechanisms can contribute to c- myc protein synthesis. a wide range of c ... | 2000 | 10637319 |
| theoretical studies of viral capsid proteins. | recent results in structural biology and increases in computer power have prompted initial theoretical studies on capsids of nonenveloped icosahedral viruses. the macromolecular assembly of 60 to 180 protein copies into a protein shell results in a structure of considerable size for molecular dynamics simulations. nonetheless, progress has been made in examining these capsid assemblies from molecular dynamics calculations and kinetic models. the goals of these studies are to understand capsid fu ... | 2000 | 10753813 |
| inhibition of human rhinovirus-induced cytokine production by ag7088, a human rhinovirus 3c protease inhibitor. | symptom severity in patients with human rhinovirus (hrv)-induced respiratory illness is associated with elevated levels of the inflammatory cytokines interleukin-6 (il-6) and il-8. ag7088 is a novel, irreversible inhibitor of the hrv 3c protease. in this study, ag7088 was tested for its antiviral activity and ability to inhibit the production of il-6 and il-8 in a human bronchial epithelial cell line, beas-2b. infection of beas-2b cells with hrv 14 resulted in the production of both infectious v ... | 2000 | 10770757 |
| anti-rhinovirus activity of 3-methylthio-5-aryl-4-isothiazolecarbonitrile derivatives. | a series of 3-methylthio-5-aryl-4-isothiazolecarbonitriles has been evaluated as anti rhinovirus agents against a panel of 17 representative human rhinovirus (hrv) serotypes, belonging to both a and b groups. no anti rhinovirus activity was detected for 3-methylthio-5-phenyl-4-isothiazolecarbonitrile (is-2). isothiazole derivatives with bulky substituents (o-bn or o-but groups) on the para position of the phenyl ring were the most effective compounds of this series. in fact, a reduction in virus ... | 2000 | 10771083 |
| substituted benzamide inhibitors of human rhinovirus 3c protease: structure-based design, synthesis, and biological evaluation. | a series of nonpeptide benzamide-containing inhibitors of human rhinovirus (hrv) 3c protease was identified using structure-based design. the design, synthesis, and biological evaluation of these inhibitors are reported. a michael acceptor was combined with a benzamide core mimicking the p1 recognition element of the natural 3cp substrate. alpha,beta-unsaturated cinnamate esters irreversibly inhibited the 3cp and displayed antiviral activity (ec(50) 0.60 microm, hrv-16 infected h1-hela cells). o ... | 2000 | 10794684 |
| influence of three-dimensional structure on the immunogenicity of a peptide expressed on the surface of a plant virus. | the influence of peptide structure on immunogenicity has been investigated by constructing a series of cowpea mosaic virus (cpmv) chimaeras expressing the 14 amino acid nim-1a epitope from human rhinovirus 14 (hrv-14) at different positions on the capsid surface. biochemical and crystallographic analysis of a cpmv/hrv chimaera expressing the nim-1a epitope inserted into the betac'-betac" loop of the s protein revealed that, although the inserted peptide was free at its c-terminus, it adopted a c ... | 2000 | 10822251 |
| allergen challenge-induced acute exudation of il-8, ecp and alpha2-macroglobulin in human rhinovirus-induced common colds. | rhinovirus infections cause exacerbations of eosinophilic airway disease. the acute effects of allergen-challenge on nasal interleukin-8 (il-8), eosinophil cationic protein (ecp), and alpha2-macroglobulin were examined in atopic subjects with common cold symptoms. twenty-three patients with seasonal allergic rhinitis were inoculated with human rhinovirus 16 outside the pollen season. diluent and allergen challenges, followed by nasal lavages, were carried out about 3 months before and 4 days aft ... | 1999 | 10836321 |
| intergeneric poliovirus recombinants for the treatment of malignant glioma. | poliovirus neuropathogenicity depends on sequences within the 5' nontranslated region of the virus. exchange of the poliovirus internal ribosomal entry site with its counterpart from human rhinovirus type 2 resulted in attenuation of neurovirulence in primates. despite deficient virus propagation in cells of neuronal origin, nonpathogenic polio recombinants retain excellent growth characteristics in cell lines derived from glial neoplasms. susceptibility of malignant glioma cells to poliovirus m ... | 2000 | 10841575 |
| capillary electrophoresis with postcolumn infectivity assay for the analysis of different serotypes of human rhinovirus (common cold virus). | differentiation of virus serotypes with capillary zone electrophoresis was demonstrated. for four serotypes of human rhinovirus (hrv2, hrv14, hrv16, hrv49), different electrophoretic mobility was achieved at ph 8.3 (borate/boric acid buffer, 100 mmol/l). addition of detergent (triton x-100-r, deoxycholate, and/or sds) to the background electrolyte was required for reduction of wall adsorption and improvement of peak shape. a major nonviral contaminant, present in all virus samples, was best sepa ... | 2000 | 10857634 |
| differential detection of rhinoviruses and enteroviruses rna sequences associated with classical immunofluorescence assay detection of respiratory virus antigens in nasopharyngeal swabs from infants with bronchiolitis. | to define the role of enteroviruses and human rhinoviruses as etiological agents in childhood bronchiolitis, clinical aspirates from 84 infants admitted to hospital with symptoms of obstructive bronchiolitis were tested by picornavirus rt-pcr assay, adenovirus pcr assay and classical immunofluorescence antigen detection of common respiratory viral agents. respiratory syncytial viruses (a&b) were detectable in 45 of 84 (53.6%) nasopharyngeal aspirates from infants with bronchiolitis, whereas coro ... | 2000 | 10861643 |