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a double-inactivated severe acute respiratory syndrome coronavirus vaccine provides incomplete protection in mice and induces increased eosinophilic proinflammatory pulmonary response upon challenge.severe acute respiratory syndrome coronavirus (sars-cov) is an important emerging virus that is highly pathogenic in aged populations and is maintained with great diversity in zoonotic reservoirs. while a variety of vaccine platforms have shown efficacy in young-animal models and against homologous viral strains, vaccine efficacy has not been thoroughly evaluated using highly pathogenic variants that replicate the acute end stage lung disease phenotypes seen during the human epidemic. using an a ...201121937658
sars-cov heptad repeat 2 is a trimer of parallel helices.in severe acute respiratory syndrome coronavirus, the envelope heptad repeat 2 (hr2) plays a critical role in viral entry. moreover, hr2 is both the target for novel antiviral therapies and, as an isolated peptide, presents a potential antiviral therapeutic. the structure of hr2, as determined by nmr spectroscopy in the presence of the co-solvent trifluoroethanol (tfe), is a trimer of parallel helices, whereas the structure of hr2, as determined by x-ray crystallography, is a tetramer of anti-pa ...201121922588
Novel system for detecting SARS coronavirus nucleocapsid protein using an ssDNA aptamer.The outbreak of severe acute respiratory syndrome (SARS) in 2002 affected thousands of people and an efficient diagnostic system is needed for accurate detection of SARS coronavirus (SARS CoV) to prevent or limit future outbreaks. Of the several SARS CoV structural proteins, the nucleocapsid protein has been shown to be a good diagnostic marker. In this study, an ssDNA aptamer that specifically binds to SARS CoV nucleocapsid protein was isolated from a DNA library containing 45-nuceotide random ...201121920814
neutralizing human monoclonal antibodies to severe acute respiratory syndrome coronavirus: target, mechanism of action, and therapeutic potential.the emergence of severe acute respiratory syndrome coronavirus (sars-cov) led to a rapid response not only to contain the outbreak but also to identify possible therapeutic interventions, including the generation of human monoclonal antibodies (hmabs). hmabs may be used therapeutically without the drawbacks of chimeric or animal abs. several different methods have been used to generate sars-cov specific neutralizing hmabs including the immunization of transgenic mice, cloning of small chain vari ...201121905149
genetic variation of the human α-2-heremans-schmid glycoprotein (ahsg) gene associated with the risk of sars-cov infection.genetic background may play an important role in the process of sars-cov infection and sars development. we found several proteins that could interact with the nucleocapsid protein of the sars coronavirus (sars-cov). α-2-heremans-schmid glycoprotein (ahsg), which is required for macrophage deactivation by endogenous cations, is associated with inflammatory regulation. cytochrome p450 family 3a (cyp4f3a) is an ω-oxidase that inactivates leukotriene b4 (ltb4) in human neutrophils and the liver. we ...201121904596
inhibition of sars pseudovirus cell entry by lactoferrin binding to heparan sulfate proteoglycans.it has been reported that lactoferrin (lf) participates in the host immune response against severe acute respiratory syndrome coronavirus (sars-cov) invasion by enhancing nk cell activity and stimulating neutrophil aggregation and adhesion. we further investigated the role of lf in the entry of sars pseudovirus into hek293e/ace2-myc cells. our results reveal that lf inhibits sars pseudovirus infection in a dose-dependent manner. further analysis suggested that lf was able to block the binding of ...201121887302
detection of bat coronaviruses from miniopterus fuliginosus in japan.bats have great potential as reservoirs for emerging viruses such as severe acute respiratory syndrome-coronavirus. in this study, bat coronaviruses (btcovs) were detected by rt-pcr from intestinal and fecal specimens of miniopterus fuliginosus breeding colonies in wakayama prefecture caves, where we previously identified bat betaherpesvirus 2. two primer sets were used for the detection of btcov: one was for the rna-dependent rna polymerase (rdrp) region and the other was for the spike (s) prot ...201121877208
detection of bat coronaviruses from miniopterus fuliginosus in japan.bats have great potential as reservoirs for emerging viruses such as severe acute respiratory syndrome-coronavirus. in this study, bat coronaviruses (btcovs) were detected by rt-pcr from intestinal and fecal specimens of miniopterus fuliginosus breeding colonies in wakayama prefecture caves, where we previously identified bat betaherpesvirus 2. two primer sets were used for the detection of btcov: one was for the rna-dependent rna polymerase (rdrp) region and the other was for the spike (s) prot ...201121877208
peptide aldehyde inhibitors challenge the substrate specificity of the sars-coronavirus main protease.sars coronavirus main protease (sars-cov m(pro)) is essential for the replication of the virus and regarded as a major antiviral drug target. the enzyme is a cysteine protease, with a catalytic dyad (cys-145/his-41) in the active site. aldehyde inhibitors can bind reversibly to the active-site sulfhydryl of sars-cov m(pro). previous studies using peptidic substrates and inhibitors showed that the substrate specificity of sars-cov m(pro) requires glutamine in the p1 position and a large hydrophob ...201121854807
stigmatized ethnicity, public health, and globalization.the prejudicial linking of infection with ethnic minority status has a long-established history, but in some ways this association may have intensified under the contemporary circumstances of the "new public health" and globalization. this study analyzes this conflation of ethnicity and disease victimization by considering the stigmatization process that occurred during the 2003 outbreak of severe acute respiratory syndrome (sars) in toronto. the attribution of stigma during the sars outbreak oc ...200821847845
the sars-cov heptad repeat 2 exhibits ph-induced helix formation.the heptad repeats 1 and 2 of sars-cov spike, termed hr1 and hr2, play critical roles in viral entry. moreover, hr1 and hr2 derived free peptides are inhibitors of sars-cov entry. in this work we used circular dichroism to show that hr2 helix formation is induced at ph 5, the ph of the endosome. in addition, we demonstrate that the hr2 helix is further stabilized at physiological ionic strengths. together, these observations provide new insight into the mechanism of sars-cov entry and suggest th ...201121835164
engineering t cells specific for a dominant sars coronavirus cd8 t cell epitope.severe acute respiratory syndrome (sars) is a highly contagious and life threatening disease, with a fatality rate of almost 10%. the etiologic agent is a novel coronavirus, sars-cov, with animal reservoirs found in bats and other wild animals and thus the possibility of re-emergence. in this study, we first investigated whether sars-specific memory t cells persist in sars-recovered individuals 6 years post-infection, demonstrating that recovered patients still possess polyfunctional sars-specif ...201121813600
on the treatment of airline travelers in mathematical models.the global spread of infectious diseases is facilitated by the ability of infected humans to travel thousands of miles in short time spans, rapidly transporting pathogens to distant locations. mathematical models of the actual and potential spread of specific pathogens can assist public health planning in the case of such an event. models should generally be parsimonious, but must consider all potentially important components of the system to the greatest extent possible. we demonstrate and disc ...201121799782
a conserved rna pseudoknot in a putative molecular switch domain of the 3'-untranslated region of coronaviruses is only marginally stable.the 3'-untranslated region (utr) of the group 2 coronavirus mouse hepatitis virus (mhv) genome contains a predicted bulged stem-loop (designated p0ab), a conserved cis-acting pseudoknot (pk), and a more distal stem-loop (designated p2). base-pairing to create the pseudoknot-forming stem (p1(pk)) is mutually exclusive with formation of stem p0a at the base of the bulged stem-loop; as a result, the two structures cannot be present simultaneously. herein, we use thermodynamic methods to evaluate th ...201121799029
under-three minute pcr: probing the limits of fast amplification.nucleic acid amplification is enormously useful to the biotechnology and clinical diagnostic communities; however, to date point-of-use pcr has been hindered by thermal cycling architectures and protocols that do not allow for near-instantaneous results. in this work we demonstrate pcr amplification of synthetic sars respiratory pathogenic targets and bacterial genomic dna in less than three minutes in a hardware configuration utilizing convenient sample loading and disposal. instead of sample m ...201121796289
expression, crystallization and preliminary crystallographic study of the c-terminal half of nsp2 from sars coronavirus.sars coronavirus (sars-cov) is the aetiological agent of the highly infectious severe acute respiratory syndrome (sars). to gain a better understanding of sars-cov replication and transcription proteins, a preliminary x-ray crystallographic study of the c-terminal domain of sars-cov nonstructural protein 2 (nsp2) is reported here. the c-terminal domain of sars-cov nsp2 was cloned, overexpressed, purified and crystallized using polyethylene glycol 5000 monomethyl ether as the precipitant; the cry ...201121795795
anti-sars-cov spike antibodies trigger infection of human immune cell via a ph- and cysteine protease-independent fc{gamma}r pathway.public health measures successfully contained outbreaks of the severe acute respiratory syndrome coronavirus (sars-cov). however, the precursor of the sars-cov remains in its natural bat reservoir and re-emergence of a human-adapted sars-like coronavirus remains a plausible public health concern. vaccination is a major strategy for containing resurgence of sars in humans and a number of vaccine candidates have been tested in experimental animal models. we previously reported that antibody elicit ...201121775467
emerging theme: cellular pdz proteins as common targets of pathogenic viruses.more than a decade ago three viral oncoproteins - adenovirus type 9 e4-orf1, human t-lymphotropic virus type 1 tax, and high-risk human papillomavirus e6 - were found to encode a related carboxyl-terminal pdz domain-binding motif (pbm) that mediates interactions with a select group of cellular pdz proteins. recent studies have shown that many other viruses also encode pbm-containing proteins that bind to cellular pdz proteins. interestingly, these recently recognized viruses include not only som ...201121775458
recent developments in anti-severe acute respiratory syndrome coronavirus chemotherapy.severe acute respiratory syndrome coronavirus (sars-cov) emerged in early 2003 to cause a very severe acute respiratory syndrome, which eventually resulted in a 10% case-fatality rate. owing to excellent public health measures that isolated focus cases and their contacts, and the use of supportive therapies, the epidemic was suppressed to the point that further cases have not appeared since 2005. however, despite intensive research since then (over 3500 publications), it remains an untreatable d ...201121765859
sars-coronavirus ancestor's foot-prints in south-east asian bat colonies and the refuge theory.one of the great challenges in the ecology of infectious diseases is to understand what drives the emergence of new pathogens including the relationship between viruses and their hosts. in the case of the emergence of severeacute respiratory syndrome coronavirus (sars-cov), several studies have shown coronavirus diversity in bats as well as the existence of sars-cov infection in apparently healthy bats, suggesting that bats may be a crucial host in the genesis of this disease. to elucidate the b ...201121763784
sars-coronavirus ancestor's foot-prints in south-east asian bat colonies and the refuge theory.one of the great challenges in the ecology of infectious diseases is to understand what drives the emergence of new pathogens including the relationship between viruses and their hosts. in the case of the emergence of severeacute respiratory syndrome coronavirus (sars-cov), several studies have shown coronavirus diversity in bats as well as the existence of sars-cov infection in apparently healthy bats, suggesting that bats may be a crucial host in the genesis of this disease. to elucidate the b ...201121763784
chimeric severe acute respiratory syndrome coronavirus (sars-cov) s glycoprotein and influenza matrix 1 efficiently form virus-like particles (vlps) that protect mice against challenge with sars-cov.sars-cov was the cause of the global pandemic in 2003 that infected over 8000 people in 8 months. vaccines against sars are still not available. we developed a novel method to produce high levels of a recombinant sars virus-like particles (vlps) vaccine containing the sars spike (s) protein and the influenza m1 protein using the baculovirus insect cell expression system. these chimeric sars vlps have a similar size and morphology to the wild type sars-cov. we tested the immunogenicity and protec ...201121762752
cyclosporin a inhibits the replication of diverse coronaviruses.low micromolar, non-cytotoxic concentrations of cyclosporin a (csa) strongly affected the replication of sars-coronavirus (sars-cov), human coronavirus 229e, and mouse hepatitis virus in cell culture, as was evident from the strong inhibition of green fluorescent protein reporter gene expression and up to 4 log reduced progeny titres. upon high-multiplicity infection, csa treatment rendered sars-cov rna and protein synthesis almost undetectable, suggesting an early block in replication. sirna-me ...201121752960
the immune responses of hla-a*0201 restricted sars-cov s peptide-specific cd8(+) t cells are augmented in varying degrees by cpg odn, polyi:c and r848.the induction of antigen specific memory cd8(+) t cells in vivo is very important to new vaccines against infectious diseases. in the present study, we aimed to evaluate the immune responses of peptide-specific cd8(+) t cells induced by hla-a*0201 restricted severe acute respiratory syndrome-associated coronavirus (sars-cov) s epitopes plus cpg oligodeoxynucleotide (cpg odn), polyi:c and r848 as adjuvants. furthermore, the generation, distribution and phenotype of long-lasting peptide-specific m ...201121745520
crystal structure and functional analysis of the sars-coronavirus rna cap 2'-o-methyltransferase nsp10/nsp16 complex.cellular and viral s-adenosylmethionine-dependent methyltransferases are involved in many regulated processes such as metabolism, detoxification, signal transduction, chromatin remodeling, nucleic acid processing, and mrna capping. the severe acute respiratory syndrome coronavirus nsp16 protein is a s-adenosylmethionine-dependent (nucleoside-2'-o)-methyltransferase only active in the presence of its activating partner nsp10. we report the nsp10/nsp16 complex structure at 2.0 å resolution, which ...201121637813
sars-cov 9b protein diffuses into nucleus, undergoes active crm1 mediated nucleocytoplasmic export and triggers apoptosis when retained in the nucleus.background: 9b is an accessory protein of the sars-cov. it is a small protein of 98 amino acids and its structure has been solved recently. 9b is known to localize in the extra-nuclear region and has been postulated to possess a nuclear export signal (nes), however the role of nes in 9b functioning is not well understood. principal findings/methodology: in this report, we demonstrate that 9b in the absence of any nuclear localization signal (nls) enters the nucleus by passive transport. using va ...201121637748
virucidal activity of a scorpion venom peptide variant mucroporin-m1 against measles, sars-cov and influenza h5n1 viruses.outbreaks of sars-cov, influenza a (h5n1, h1n1) and measles viruses in recent years have raised serious concerns about the measures available to control emerging and re-emerging infectious viral diseases. effective antiviral agents are lacking that specifically target rna viruses such as measles, sars-cov and influenza h5n1 viruses, and available vaccinations have demonstrated variable efficacy. therefore, the development of novel antiviral agents is needed to close the vaccination gap and silen ...201121620914
inhibitors of sars-3cl(pro): virtual screening, biological evaluation, and molecular dynamics simulation studies.sars-cov from the coronaviridae family has been identified as the etiological agent of severe acute respiratory syndrome (sars), a highly contagious upper respiratory disease that reached epidemic status in 2002. sars-3cl(pro), a cysteine protease indispensible to the viral life cycle, has been identified as one of the key therapeutic targets against sars. a combined ligand and structure-based virtual screening was carried out against the asinex platinum collection. multiple low micromolar inhib ...201121604711
fully human monoclonal antibody directed to proteolytic cleavage site in severe acute respiratory syndrome (sars) coronavirus s protein neutralizes the virus in a rhesus macaque sars model.background. there is still no effective method to prevent or treat severe acute respiratory syndrome (sars), which is caused by sars coronavirus (cov). in the present study, we evaluated the efficacy of a fully human monoclonal antibody capable of neutralizing sars-cov in vitro in a rhesus macaque model of sars. methods. the antibody 5h10 was obtained by vaccination of km mice bearing human immunoglobulin genes with escherichiacoli-producing recombinant peptide containing the dominant epitope of ...201121592986
fully human monoclonal antibody directed to proteolytic cleavage site in severe acute respiratory syndrome (sars) coronavirus s protein neutralizes the virus in a rhesus macaque sars model.background. there is still no effective method to prevent or treat severe acute respiratory syndrome (sars), which is caused by sars coronavirus (cov). in the present study, we evaluated the efficacy of a fully human monoclonal antibody capable of neutralizing sars-cov in vitro in a rhesus macaque model of sars. methods. the antibody 5h10 was obtained by vaccination of km mice bearing human immunoglobulin genes with escherichiacoli-producing recombinant peptide containing the dominant epitope of ...201121592986
identification of rna pseudoknot-binding ligand that inhibits the -1 ribosomal frameshifting of sars-coronavirus by structure-based virtual screening.programmed -1 ribosomal frameshifting (-1 rf) is an essential regulating mechanism of translation used by sars-cov (severe acute respiratory syndrome coronavirus) to synthesize the key replicative proteins encoded by two overlapping open reading frames. the integrity of rna pseudoknot stability and structure in -1 rf site is an important for efficient -1 rf. thus, small molecules interacting with high affinity and selectivity with the rna pseudoknot in -1 rf site of sars-cov (sars-pseudoknot), w ...201121591761
protocol for recombinant rbd-based sars vaccines: protein preparation, animal vaccination and neutralization detection.based on their safety profile and ability to induce potent immune responses against infections, subunit vaccines have been used as candidates for a wide variety of pathogens (1-3). since the mammalian cell system is capable of post-translational modification, thus forming properly folded and glycosylated proteins, recombinant proteins expressed in mammalian cells have shown the greatest potential to maintain high antigenicity and immunogenicity (4-6). although no new cases of sars have been repo ...201121587153
lack of peripheral memory b cell responses in recovered patients with severe acute respiratory syndrome: a six-year follow-up study.six years have passed since the outbreak of severe acute respiratory syndrome (sars). previous studies indicated that specific abs to sars-related coronavirus (sars-cov) waned over time in recovered sars patients. it is critical to find out whether a potential anamnestic response, as seen with other viral infections, exists to protect a person from reinfection in case of another sars outbreak. recovered sars patients were followed up to 6 y to estimate the longevity of specific ab. the specific ...201121576510
angiotensin-converting enzyme 2 ectodomain shedding cleavage-site identification: determinants and constraints.adam17, also known as tumor necrosis factor α-converting enzyme, is involved in the ectodomain shedding of many integral membrane proteins. we have previously reported that adam17 is able to mediate the cleavage secretion of the ectodomain of human angiotensin-converting enzyme 2 (ace2), a functional receptor for the severe acute respiratory syndrome coronavirus. in this study, we demonstrate that purified recombinant human adam17 is able to cleave a 20-amino acid peptide mimetic corresponding t ...201121563828
sars-cov accessory protein 3b induces ap-1 transcriptional activity through activation of jnk and erk pathways.the outbreak of severe acute respiratory syndrome (sars) in 2003 in china, characterized by atypical pneumonia, was associated with the emergence of a novel coronavirus named severe acute respiratory syndrome coronavirus (sars-cov). eight accessory proteins of sars coronavirus were the suspected players in the pathogenesis of the virus. among them, protein 3b localizes to the nucleus and behaves as an interferon antagonist by inhibiting irf3 activation. however, the effect of 3b on the activity ...201121561061
using a pan-viral microarray assay (virochip) to screen clinical samples for viral pathogens.the diagnosis of viral causes of many infectious diseases is difficult due to the inherent sequence diversity of viruses as well as the ongoing emergence of novel viral pathogens, such as sars coronavirus and 2009 pandemic h1n1 influenza virus, that are not detectable by traditional methods. to address these challenges, we have previously developed and validated a pan-viral microarray platform called the virochip with the capacity to detect all known viruses as well as novel variants on the basi ...201121559002
interference of ribosomal frameshifting by antisense peptide nucleic acids suppresses sars coronavirus replication.the programmed -1 ribosomal frameshifting (-1 prf) utilized by eukaryotic rna viruses plays a crucial role for the controlled, limited synthesis of viral rna replicase polyproteins required for genome replication. the viral rna replicase polyproteins of severe acute respiratory syndrome coronavirus (sars-cov) are encoded by the two overlapping open reading frames 1a and 1b, which are connected by a -1 prf signal. we evaluated the antiviral effects of antisense peptide nucleic acids (pnas) target ...201121549154
locapep: localization of epitopes on protein surfaces using peptides from phage display libraries.the use of peptides from a phage display library selected by binding to a given antibody is a widespread technique to probe epitopes of antigenic proteins. however, the identification of interaction sites mimicked by these peptides on the antigen surface is a difficult task. locapep is a computer program developed to localize epitopes using a new clusters algorithm that focuses on protein surface properties. the program is constructed with the aim of providing a flexible computational tool for p ...201121539309
activation and maturation of sars-cov main protease.the worldwide outbreak of the severe acute respiratory syndrome (sars) in 2003 was due to the transmission of sars coronavirus (sars-cov). the main protease (m(pro)) of sars-cov is essential for the viral life cycle, and is considered to be an attractive target of anti-sars drug development. as a key enzyme for proteolytic processing of viral polyproteins to produce functional non-structure proteins, m(pro) is first auto-cleaved out of polyproteins. the monomeric form of m(pro) is enzymatically ...201121533772
comparative pathogenesis of three human and zoonotic sars-cov strains in cynomolgus macaques.the severe acute respiratory syndrome (sars) epidemic was characterized by increased pathogenicity in the elderly due to an early exacerbated innate host response. sars-cov is a zoonotic pathogen that entered the human population through an intermediate host like the palm civet. to prevent future introductions of zoonotic sars-cov strains and subsequent transmission into the human population, heterologous disease models are needed to test the efficacy of vaccines and therapeutics against both la ...201121533129
the adp-ribose-1"-monophosphatase domains of sars-coronavirus and human coronavirus 229e mediate resistance to antiviral interferon responses.several plus strand rna viruses encode proteins containing macrodomains. these domains possess adp-ribose-1-phosphatase (adrp) activity and/or bind poly(adp-ribose), poly(a), or poly(g). the relevance of these activities in the viral life cycle has not yet been resolved. here, we report that genetically engineered mutants of sars-coronavirus (sars-cov) and human coronavirus 229e (hcov-229e) expressing adrp-deficient macrodomains displayed an increased sensitivity to the antiviral effect of inter ...201121525212
subcellular location and topology of severe acute respiratory syndrome coronavirus envelope protein.severe acute respiratory syndrome (sars) coronavirus (cov) envelope (e) protein is a transmembrane protein. several subcellular locations and topological conformations of e protein have been proposed. to identify the correct ones, polyclonal and monoclonal antibodies specific for the amino or the carboxy terminus of e protein, respectively, were generated. e protein was mainly found in the endoplasmic reticulum-golgi intermediate compartment (ergic) of cells transfected with a plasmid encoding e ...201121524776
viral infections in workers in hospital and research laboratory settings: a comparative review of infection modes and respective biosafety aspects.to compare modes and sources of infection and clinical and biosafety aspects of accidental viral infections in hospital workers and research laboratory staff reported in scientific articles.201121497126
the school of nature: iv. learning from viruses.during the co-evolution of viruses and their hosts, the latter have equipped themselves with an elaborate immune system to defend themselves from the invading viruses. in order to establish a successful infection, replicate and persist in the host, viruses have evolved numerous strategies to counter and evade host antiviral immune responses as well as exploit them for productive viral replication. these strategies include those that modulate signaling mediated by cell surface receptors. despite ...201021487503
virtual screening identification of novel severe acute respiratory syndrome 3c-like protease inhibitors and in vitro confirmation.the 3c-like protease (3cl(pro)) of severe acute respiratory syndrome associated coronavirus (sars-cov) is vital for sars-cov replication and is a promising drug target. structure based virtual screening of 308307 chemical compounds was performed using the computation tool autodock 3.0.5 on a wisdom production environment. the top 1468 ranked compounds with free binding energy ranging from -14.0 to -17.09kcalmol(-1) were selected to check the hydrogen bond interaction with amino acid residues in ...201121470860
pika provides an adjuvant effect to induce strong mucosal and systemic humoral immunity against sars-cov.severe acute respiratory syndrome (sars) is a deadly infectious disease caused by sars coronavirus (sars-cov). inactivated sars-cov has been explored as a vaccine against sars-cov. however, safe and potent adjuvants, especially with more efficient and economical needle-free vaccination are always needed more urgently in a pandemic. the development of a safe and effective mucosal adjuvant and vaccine for prevention of emergent infectious diseases such as sars will be an important advancement. pik ...201121468931
inhibition of ebola virus entry by a c-peptide targeted to endosomes.ebola virus (ebov) and marburg virus (marv) (filoviruses) are the causative agents of severe hemorrhagic fever. infection begins with uptake of particles into cellular endosomes, where the viral envelope glycoprotein (gp) catalyzes fusion between the viral and host cell membranes. this fusion event is thought to involve conformational rearrangements of the transmembrane subunit (gp2) of the envelope spike that ultimately result in formation of a six-helix bundle by the n- and c-terminal heptad r ...201121454542
identification of a golgi complex-targeting signal in the cytoplasmic tail of the severe acute respiratory syndrome coronavirus envelope protein.the 2003 global outbreak of progressive respiratory failure was caused by a newly emerged virus, severe acute respiratory syndrome coronavirus (sars-cov). in contrast to many well-studied enveloped viruses that assemble and bud at the plasma membrane, coronaviruses assemble by budding into the lumen of the endoplasmic reticulum-golgi intermediate compartment and are released from the cell by exocytosis. for this to occur, the viral envelope proteins must be efficiently targeted to the golgi regi ...201121450821
development of reflective biosensor using fabrication of functionalized photonic nanocrystals.photonic crystals (pcs) are periodic dielectric structures that have a band-gap that forbids propagation of a certain range of wavelengths of light. this property enables control of light with remarkable facility by modification of the band-gaps and produce effects that are impossible with conventional optics. using chemically functionalized pcs, where the chemical functional group consists of amine and carboxyl group, in conjunction with a biomolecular probe material, the detection of pathogens ...201121446513
different host cell proteases activate the sars-coronavirus spike-protein for cell-cell and virus-cell fusion.severe acute respiratory syndrome coronavirus (sars-cov) poses a considerable threat to human health. activation of the viral spike (s)-protein by host cell proteases is essential for viral infectivity. however, the cleavage sites in sars-s and the protease(s) activating sars-s are incompletely defined. we found that r667 was dispensable for sars-s-driven virus-cell fusion and for sars-s-activation by trypsin and cathepsin l in a virus-virus fusion assay. mutation t760r, which optimizes the mini ...201121435673
control of severe acute respiratory syndrome in singapore.a severe acute respiratory syndrome (sars) outbreak occurred in singapore from february to may 2003. a high vigilance for the disease, frequent and regular temperature monitoring, early case identification and isolation of patients, as well as tracing and home quarantine of contacts, played major roles in controlling the outbreak. hospitals were dedicated to the screening and treatment of sars patients. within and between hospitals, movement by healthcare workers, patients and visitors were rest ...200521432128
improved prediction of mhc class i binders/non-binders peptides through artificial neural network using variable learning rate: sars corona virus, a case study.fundamental step of an adaptive immune response to pathogen or vaccine is the binding of short peptides (also called epitopes) to major histocompatibility complex (mhc) molecules. the various prediction algorithms are being used to capture the mhc peptide binding preference, allowing the rapid scan of entire pathogen proteomes for peptide likely to bind mhc, saving the cost, effort, and time. however, the number of known binders/non-binders (bnb) to a specific mhc molecule is limited in many cas ...201121431562
an optimal cis-replication stem-loop iv in the 5' untranslated region of the mouse coronavirus genome extends 16 nucleotides into open reading frame 1.the 288-nucleotide (nt) 3' untranslated region (utr) in the genome of the bovine coronavirus (bcov) and 339-nt 3' utr in the severe acute respiratory syndrome (sars) coronavirus (scov) can each replace the 301-nt 3' utr in the mouse hepatitis coronavirus (mhv) for virus replication, thus demonstrating common 3' cis-replication signals. here, we show that replacing the 209-nt mhv 5' utr with the ~63%-sequence-identical 210-nt bcov 5' utr by reverse genetics does not yield viable virus, suggesting ...201121430057
development and rna-synthesizing activity of coronavirus replication structures in the absence of protein synthesis.the rna replication and transcription complex of coronaviruses is associated with an elaborate reticulovesicular network (rvn) of modified endoplasmic reticulum. using cycloheximide and puromycin, we have studied the effect of translation inhibition on the rna synthesis of severe acute respiratory syndrome coronavirus and mouse hepatitis virus. both inhibitors prevented the usual exponential increase in viral rna synthesis, with immunofluorescence and electron microscopy indicating that rvn deve ...201121430047
a virus-binding hot spot on human angiotensin-converting enzyme 2 is critical for binding of two different coronaviruses.how viruses evolve to select their receptor proteins for host cell entry is puzzling. we recently determined the crystal structures of nl63 coronavirus (nl63-cov) and sars coronavirus (sars-cov) receptor-binding domains (rbds), each complexed with their common receptor, human angiotensin-converting enzyme 2 (hace2), and proposed the existence of a virus-binding hot spot on hace2. here we investigated the function of this hypothetical hot spot using structure-guided biochemical and functional ass ...201121411533
crystallization and diffraction analysis of the sars coronavirus nsp10-nsp16 complex.to date, the sars coronavirus is the only known highly pathogenic human coronavirus. in 2003, it was responsible for a large outbreak associated with a 10% fatality rate. this positive rna virus encodes a large replicase polyprotein made up of 16 gene products (nsp1-16), amongst which two methyltransferases, nsp14 and nsp16, are involved in viral mrna cap formation. the crystal structure of nsp16 is unknown. nsp16 is an rna-cap adomet-dependent (nucleoside-2'-o-)-methyltransferase that is only a ...201121393853
dynamically-driven inactivation of the catalytic machinery of the sars 3c-like protease by the n214a mutation on the extra domain.despite utilizing the same chymotrypsin fold to host the catalytic machinery, coronavirus 3c-like proteases (3clpro) noticeably differ from picornavirus 3c proteases in acquiring an extra helical domain in evolution. previously, the extra domain was demonstrated to regulate the catalysis of the sars-cov 3clpro by controlling its dimerization. here, we studied n214a, another mutant with only a doubled dissociation constant but significantly abolished activity. unexpectedly, n214a still adopts the ...201121390281
the solution structure of coronaviral stem-loop 2 (sl2) reveals a canonical cuyg tetraloop fold.the transcription and replication of the severe acute respiratory syndrome (sars) coronavirus (sars-cov) is regulated by specific viral genome sequences within 5'- and 3'-untranslated regions (5'-utr and 3'-utr). here we report the solution structure of 5'-utr derived stem-loop 2 (sl2) of sars-cov determined by nmr spectroscopy. the highly conserved pentaloop of sl2 is stacked on 5-bp stem and adopts a canonical cuyg tetraloop fold with the 3' nucleotide (u51) flipped out of the stack. the signi ...201121382373
longitudinal profiles of immunoglobulin g antibodies against severe acute respiratory syndrome coronavirus components and neutralizing activities in recovered patients.immunological memory is the basis for vaccination. currently, the longitudinal profiles of antibody responses in recovered severe acute respiratory syndrome (sars) patients have not been fully characterized.201121366405
plp2 of mouse hepatitis virus a59 (mhv-a59) targets tbk1 to negatively regulate cellular type i interferon signaling pathway.coronaviruses such as severe acute respiratory syndrome (sars) coronavirus (scov) and mouse hepatitis virus a59 (mhv-a59) have evolved strategies to disable the innate immune system for productive replication and spread of infection. we have previously shown that papain-like protease domain 2 (plp2), a catalytic domain of the nonstructural protein 3 (nsp3) of mhv-a59, encodes a deubiquitinase (dub) and inactivates ifn regulatory factor 3 (irf3) thereby the type i interferon (ifn) response.201121364999
emodin inhibits current through sars-associated coronavirus 3a protein.the open-reading-frame 3a of sars coronavirus (sars-cov) had been demonstrated previously to form a cation-selective channel that may become expressed in the infected cell and is then involved in virus release. drugs that inhibit the ion channel formed by the 3a protein can be expected to inhibit virus release, and would be a source for the development of novel therapeutic agents. here we demonstrate that emodin can inhibit the 3a ion channel of coronavirus sars-cov and hcov-oc43 as well as viru ...201121356245
inhibition of severe acute respiratory syndrome coronavirus replication in a lethal sars-cov balb/c mouse model by stinging nettle lectin, urtica dioica agglutinin.urtica dioica agglutinin (uda) is a small plant monomeric lectin, 8.7 kda in size, with an n-acetylglucosamine specificity that inhibits viruses from nidovirales in vitro. in the current study, we first examined the efficacy of uda on the replication of different sars-cov strains in vero 76 cells. uda inhibited virus replication in a dose-dependent manner and reduced virus yields of the urbani strain by 90% at 1.1 ± 0.4 µg/ml in vero 76 cells. then, uda was tested for efficacy in a lethal sars-c ...201121338626
validation of assays to monitor immune responses in the syrian golden hamster (mesocricetus auratus).the syrian golden hamster (mesocricetus auratus) is a valuable but under-utilized animal model for studies of human viral pathogens such as bunyaviruses, arenaviruses, flaviviruses, henipaviruses, and sars-coronavirus. a lack of suitable reagents and specific assays for monitoring host responses has limited the use of this animal model to clinical observations, pathology and humoral immune responses. the objective of this study was to establish and validate assays to monitor host immune response ...201121334343
validation of assays to monitor immune responses in the syrian golden hamster (mesocricetus auratus).the syrian golden hamster (mesocricetus auratus) is a valuable but under-utilized animal model for studies of human viral pathogens such as bunyaviruses, arenaviruses, flaviviruses, henipaviruses, and sars-coronavirus. a lack of suitable reagents and specific assays for monitoring host responses has limited the use of this animal model to clinical observations, pathology and humoral immune responses. the objective of this study was to establish and validate assays to monitor host immune response ...201121334343
benefits of random-priming: exhaustive survey of a cdna library from lung tissue of a sars patient.the severe acute respiratory syndrome (sars) leads to severe injury in the lungs with multiple factors, though the pathogenesis is still largely unclear. this paper describes the particular analyses of the transcriptome of human lung tissue that was infected by sars-associated coronavirus (sars-cov). random primers were used to produce ests from total rna samples of the lung tissue. the result showed a high diversity of the transcripts, covering much of the human genome, including loci which do ...201121328370
evidence that tmprss2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response.the spike (s) protein of the severe acute respiratory syndrome coronavirus (sars-cov) can be proteolytically activated by cathepsins b and l upon viral uptake into target cell endosomes. in contrast, it is largely unknown whether host cell proteases located in the secretory pathway of infected cells and/or on the surface of target cells can cleave sars s. we along with others could previously show that the type ii transmembrane protease tmprss2 activates the influenza virus hemagglutinin and the ...201121325420
distinct severe acute respiratory syndrome coronavirus-induced acute lung injury pathways in two different nonhuman primate species.acute lung injury (ali) and acute respiratory distress syndrome (ards), caused by influenza a virus h5n1 and severe acute respiratory syndrome coronavirus (sars-cov), supposedly depend on activation of the oxidative-stress machinery that is coupled with innate immunity, resulting in a strong proinflammatory host response. inflammatory cytokines, such as interleukin 1ß (il-1ß), il-8, and il-6, play a major role in mediating and amplifying ali/ards by stimulating chemotaxis and activation of neutr ...201121325418
distinct severe acute respiratory syndrome coronavirus-induced acute lung injury pathways in two different nonhuman primate species.acute lung injury (ali) and acute respiratory distress syndrome (ards), caused by influenza a virus h5n1 and severe acute respiratory syndrome coronavirus (sars-cov), supposedly depend on activation of the oxidative-stress machinery that is coupled with innate immunity, resulting in a strong proinflammatory host response. inflammatory cytokines, such as interleukin 1ß (il-1ß), il-8, and il-6, play a major role in mediating and amplifying ali/ards by stimulating chemotaxis and activation of neutr ...201121325418
down-regulation of granulocyte-macrophage colony-stimulating factor by 3c-like proteinase in transfected a549 human lung carcinoma cells.severe acute respiratory syndrome (sars) is a severe respiratory illness caused by a novel virus, the sars coronavirus (sars-cov). 3c-like protease (3clpro) of sars-cov plays a role in processing viral polypeptide precursors and is responsible of viral maturation. however, the function of 3clpro in host cells remains unknown. this study investigated how the 3clpro affected the secretion of cytokines in the gene-transfected cells.201121324206
identification and characterization of three novel small interference rnas that effectively down-regulate the isolated nucleocapsid gene expression of sars coronavirus.nucleocapsid (n) protein of severe acute respiratory syndrome-associated coronavirus (sars-cov) is a major pathological determinant in the host that may cause host cell apoptosis, upregulate the proinflammatory cytokine production, and block innate immune responses. therefore, n gene has long been thought an ideal target for the design of small interference rna (sirna). sirna is a class of small non-coding rnas with a size of 21-25nt that functions post-transcriptionally to block targeted gene e ...201121317844
the leader proteinase of foot-and-mouth disease virus negatively regulates the type i interferon pathway by acting as a viral deubiquitinase.the leader proteinase (l(pro)) of foot-and-mouth disease virus (fmdv) is a papain-like proteinase that plays an important role in fmdv pathogenesis. previously, it has been shown that l(pro) is involved in the inhibition of the type i interferon (ifn) response by fmdv. however, the underlying mechanisms remain unclear. here we demonstrate that fmdv lb(pro), a shorter form of l(pro), has deubiquitinating activity. sequence alignment and structural bioinformatics analyses revealed that the catalyt ...201121307201
development of anti-viral agents using molecular modeling and virtual screening techniques.computational chemistry has always played a key role in anti-viral drug development. the challenges and the quickly rising public interest when a virus is becoming a threat has significantly influenced computational drug discovery. the most obvious example is anti-aids research, where hiv protease and reverse transcriptase have triggered enormous efforts in developing and improving computational methods. methods applied to anti-viral research include (i) ligand-based approaches that rely on know ...201121303343
epithelial cells lining salivary gland ducts are early target cells of severe acute respiratory syndrome coronavirus infection in the upper respiratory tracts of rhesus macaques.the shedding of severe acute respiratory syndrome coronavirus (sars-cov) into saliva droplets plays a critical role in viral transmission. the source of high viral loads in saliva, however, remains elusive. here we investigate the early target cells of infection in the entire array of respiratory tissues in chinese macaques after intranasal inoculations with a single-cycle pseudotyped virus and a pathogenic sars-cov. we found that angiotensin-converting enzyme 2-positive (ace2(+)) cells were wid ...201121289121
epithelial cells lining salivary gland ducts are early target cells of severe acute respiratory syndrome coronavirus infection in the upper respiratory tracts of rhesus macaques.the shedding of severe acute respiratory syndrome coronavirus (sars-cov) into saliva droplets plays a critical role in viral transmission. the source of high viral loads in saliva, however, remains elusive. here we investigate the early target cells of infection in the entire array of respiratory tissues in chinese macaques after intranasal inoculations with a single-cycle pseudotyped virus and a pathogenic sars-cov. we found that angiotensin-converting enzyme 2-positive (ace2(+)) cells were wid ...201121289121
severe acute respiratory syndrome coronavirus papain-like protease suppressed alpha interferon-induced responses through downregulation of extracellular signal-regulated kinase 1-mediated signalling pathways.severe acute respiratory syndrome coronavirus (sars-cov) papain-like protease (plpro), a deubiquitinating enzyme, reportedly blocks poly i?:?c-induced activation of interferon regulatory factor 3 and nuclear factor kappa b, reducing interferon (ifn) induction. this study investigated type i ifn antagonist mechanism of plpro in human promonocytes. plpro antagonized ifn-a-induced responses such as interferon-stimulated response element- and ap-1-driven promoter activation, protein kinase r, 2'-5'- ...201121270289
a new method for monitoring and forecasting the case-fatality rate in ongoing epidemics and its evaluation using published data of sars in 2003, h1n1 pandemic in 2009/2010, hand-foot-mouth disease in china in 2009/2010, and cholera in haiti in 2010. 201121266767
inactivation of surrogate coronaviruses on hard surfaces by health care germicides.in the 2003 severe acute respiratory syndrome outbreak, finding viral nucleic acids on hospital surfaces suggested surfaces could play a role in spread in health care environments. surface disinfection may interrupt transmission, but few data exist on the effectiveness of health care germicides against coronaviruses on surfaces.201121256627
distinct patterns of ifitm-mediated restriction of filoviruses, sars coronavirus, and influenza a virus.interferon-inducible transmembrane proteins 1, 2, and 3 (ifitm1, 2, and 3) are recently identified viral restriction factors that inhibit infection mediated by the influenza a virus (iav) hemagglutinin (ha) protein. here we show that ifitm proteins restricted infection mediated by the entry glycoproteins (gp(1,2)) of marburg and ebola filoviruses (marv, ebov). consistent with these observations, interferon-β specifically restricted filovirus and iav entry processes. ifitm proteins also inhibited ...201121253575
reverse transcription polymerase chain reaction and electrospray ionization mass spectrometry for identifying acute viral upper respiratory tract infections.diagnosis of respiratory viruses traditionally relies on culture or antigen detection. we aimed to demonstrate capacity of the reverse transcription polymerase chain reaction/electrospray ionization mass spectrometry (rt-pcr/esi-ms) platform to identify clinical relevant respiratory viruses in nasopharyngeal aspirate (npa) samples and compare the diagnostic performance characteristics relative to conventional culture- and antigen-based methods. an rt-pcr/esi-ms respiratory virus surveillance kit ...201121251562
development of a molecular-beacon-based multi-allelic real-time rt-pcr assay for the detection of human coronavirus causing severe acute respiratory syndrome (sars-cov): a general methodology for detecting rapidly mutating viruses.emerging infectious diseases have caused a global effort for development of fast and accurate detection techniques. the rapidly mutating nature of viruses presents a major difficulty, highlighting the need for specific detection of genetically diverse strains. one such infectious agent is sars-associated coronavirus (sars-cov), which emerged in 2003. this study aimed to develop a real-time rt-pcr detection assay specific for sars-cov, taking into account its intrinsic polymorphic nature due to g ...201121221674
gaps remain in china's ability to detect emerging infectious diseases despite advances since the onset of sars and avian flu.early detection of emerging infections in china is critical to the health of the 1.3 billion chinese people and to the world. china's surveillance system for endemic infectious diseases has improved greatly since 2003, but the country's ability to conduct surveillance for laboratory-confirmed infections remains underdeveloped. this is dangerous for china, the world's most populous country, which has been the focus of global attention since outbreaks of severe acute respiratory syndrome (sars) an ...201121209448
liberation of sars-cov main protease from the viral polyprotein: n-terminal autocleavage does not depend on the mature dimerization mode.the main protease (m(pro)) plays a vital role in proteolytic processing of the polyproteins in the replicative cycle of sars coronavirus (sars-cov). dimerization of this enzyme has been shown to be indispensable for trans-cleavage activity. however, the auto-processing mechanism of m(pro), i.e. its own release from the polyproteins through autocleavage, remains unclear. this study elucidates the relationship between the n-terminal autocleavage activity and the dimerization of "immature" m(pro). ...201021203998
new nsp8 isoform suggests mechanism for tuning viral rna synthesis.during severe acute respiratory syndrome coronavirus (sars-cov) infection, the activity of the replication/transcription complexes (rtc) quickly peaks at 6 hours post infection (h.p.i) and then diminishes significantly in the late post-infection stages. this "down-up-down" regulation of rna synthesis distinguishes different viral stages: primary translation, genome replication, and finally viron assembly. regarding the nsp8 as the primase in rna synthesis, we confirmed that the proteolysis produ ...201021203988
three-dimensional domain swapping as a mechanism to lock the active conformation in a super-active octamer of sars-cov main protease.proteolytic processing of viral polyproteins is indispensible for the lifecycle of coronaviruses. the main protease (m(pro)) of sars-cov is an attractive target for anti-sars drug development as it is essential for the polyprotein processing. m(pro) is initially produced as part of viral polyproteins and it is matured by autocleavage. here, we report that, with the addition of an n-terminal extension peptide, m(pro) can form a domain-swapped dimer. after complete removal of the extension peptide ...201021203949
intranasal immunization with plasmid dna encoding spike protein of sars-coronavirus/polyethylenimine nanoparticles elicits antigen-specific humoral and cellular immune responses.immunization with the spike protein (s) of severe acute respiratory syndrome (sars)-coronavirus (cov) in mice is known to produce neutralizing antibodies and to prevent the infection caused by sars-cov. polyethylenimine 25k (pei) is a cationic polymer which effectively delivers the plasmid dna.201021194475
development of anti-viral agents using molecular modeling and virtual screening techniques.computational chemistry has always played a key role in anti-viral drug development. the challenges and the quickly rising public interest when a virus is becoming a threat has significantly influenced computational drug discovery. the most obvious example is anti-aids research, where hiv protease and reverse transcriptase have triggered enormous efforts in developing and improving computational methods. methods applied to anti-viral research include (i) ligand-based approaches that rely on know ...201021189123
(1)h, (13)c and (15)n resonance assignments of sars-cov main protease n-terminal domain.the main protease (m(pro)) of severe acute respiratory syndrome coronavirus (sars-cov) plays an essential role in the extensive proteolytic processing of the viral polyproteins (pp1a and pp1ab), and it is an important target for anti-sars drug development. sars-cov m(pro) is composed of a catalytic n-terminal domain and an α-helical c-terminal domain linked by a long loop. even though the n-terminal domain of sars-cov m(pro) adopts a similar chymotrypsin-like fold as that of piconavirus 3c prote ...201021181312
interferon interplay helps tissue cells to cope with sars-coronavirus infection.sars coronavirus (sars-cov), the causative agent of severe acute respiratory syndrome, is a versatile pathogen armed with a host of factors countering the antiviral type i interferon (ifn) system. hence, tissue cells infected with sars-cov are unable to launch an ifn response. plasmacytoid dendritic cells, however, produce high levels of ifn after infection. we recently demonstrated that minute amounts of ifn applied before infection (ifn priming) can ameliorate the ifn response of tissue cells ...201021178452
[study on the changing regularity of special antibody and expression of stomach and enteric involvement on sars-coronavirus infection in the recovery period of severe acute respiratory syndrome.]objective: to study the change of special antibodies titer igg, igm and nucleocaspid to sars coronavirus (cov) and observing the expression of stomach and enteric involvement on sars-cov infection by monoclonal antibody against n protein of sars-cov in the 7-year recovery period among family clustering cases of severe acute respiratory syndrome. methods: special antibody titer to sars-cov of 14 patients from 5 different families and their 10 kinfolks continuously tested by ifa and antigen-captur ...201021162846
on the mechanisms of bananin activity against severe acute respiratory syndrome coronavirus.in a previous study, severe acute respiratory syndrome coronavirus (sars-cov) was cultured in the presence of bananin, an effective adamantane-related molecule with antiviral activity. in the present study, we show that all bananin-resistant variants exhibit mutations in helicase and membrane protein, although no evidence of bananin interference on their mutual interaction has been found. a structural analysis on protein sequence mutations found in sars-cov bananin-resistant variants was perform ...201021134131
detection of sars coronavirus.the emergence of severe acute respiratory syndrome (sars) and its subsequent worldwide spread challenged the global public health community to confront a novel infectious disease. the infection is caused by a coronavirus of animal origin. in this epidemic, molecular detections of sars coronavirus rna were shown to be useful for the early diagnosis of sars. although this pathogen was eradicated in humans, sars or sars-like viruses might reemerge from animals or from laboratory incidents. in this ...201121116811
simultaneous detection and differentiation of respiratory syncytial virus and other respiratory viral pathogens.rapid and accurate detection of respiratory syncytial virus (rsv) provides pathogen-specific diagnosis, allows implementation of appropriate infection control measures, and improves patient management. one diagnostic challenge is that respiratory infections, which can be caused by several viral pathogens including rsv, usually present with similar signs and symptoms that are nearly indistinguishable by clinical diagnosis. we have described in the chapter a rapid, high-throughput laboratory techn ...201121116808
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
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
[progress in structural studies of larger proteins by the sail-nmr method]. 200921089580
preparation and characterization of polyclonal antibody against severe acute respiratory syndrome-associated coronavirus spike protein.a truncated gene (designated s1) encoding the receptor-binding domain (rbd) in the spike (s) protein of severe acute respiratory syndrome-associated coronavirus (sars-cov) was amplified by pcr. the gene was cloned into prokaryotic expression vector pgex-6p-1, resulting in a recombinant plasmid pgex-sars-s1. subsequently, pgex-sars-s1 was transformed into host cells bl21(de3)plyss, and the expression of the s1 protein was induced by isopropyl β-d-thiogalactoside (iptg). polyclonal antibody agains ...201021087096
increase of sars-cov 3cl peptidase activity due to macromolecular crowding effects in the milieu composition.the 3c-like peptidase of the severe acute respiratory syndrome virus (sars-cov) is strictly required for viral replication, thus being a potential target for the development of antiviral agents. in contrast to monomeric picornavirus 3c peptidases, sars-cov 3clpro exists in equilibrium between the monomer and dimer forms in solution, and only the dimer is proteolytically active in dilute buffer solutions. in this study, the increase of sars-cov 3clpro peptidase activity in presence of kosmotropic ...201021087086
zn(2+) inhibits coronavirus and arterivirus rna polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture.increasing the intracellular zn(2+) concentration with zinc-ionophores like pyrithione (pt) can efficiently impair the replication of a variety of rna viruses, including poliovirus and influenza virus. for some viruses this effect has been attributed to interference with viral polyprotein processing. in this study we demonstrate that the combination of zn(2+) and pt at low concentrations (2 µm zn(2+) and 2 µm pt) inhibits the replication of sars-coronavirus (sars-cov) and equine arteritis virus ...201021079686
nucleic acid amplification-based diagnosis of respiratory virus infections.the appearance of eight new respiratory viruses in the human population in the past 9 years, including two new pandemics (sars coronavirus in 2003 and swine-origin influenza a/h1n1 in 2009), has tested the ability of virology laboratories to develop diagnostic tests to identify these viruses. nucleic acid amplification tests (nats) that first appeared two decades ago have been developed for both conventional and emerging viruses and now form the backbone of the clinical laboratory. nats provide ...201021073292
a transmembrane serine protease is linked to the severe acute respiratory syndrome coronavirus receptor and activates virus entry.spike (s) proteins, the defining projections of the enveloped coronaviruses (covs), mediate cell entry by connecting viruses to plasma membrane receptors and by catalyzing subsequent virus-cell membrane fusions. the latter membrane fusion requires an s protein conformational flexibility that is facilitated by proteolytic cleavages. we hypothesized that the most relevant cellular proteases in this process are those closely linked to host cell receptors. the primary receptor for the human severe a ...201021068237
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