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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
The SARS-coronavirus nsp7+nsp8 complex is a unique multimeric RNA polymerase capable of both de novo initiation and primer extension.Uniquely among RNA viruses, replication of the ~30-kb SARS-coronavirus genome is believed to involve two RNA-dependent RNA polymerase (RdRp) activities. The first is primer-dependent and associated with the 106-kDa non-structural protein 12 (nsp12), whereas the second is catalysed by the 22-kDa nsp8. This latter enzyme is capable of de novo initiation and has been proposed to operate as a primase. Interestingly, this protein has only been crystallized together with the 10-kDa nsp7, forming a hex ...201122039154
respiratory health issues in the asia-pacific region: an overview.the asia-pacific region is home to a large heterogeneous population whose respiratory health is influenced by diverse social, economic and environmental factors. despite this variability, the most prevalent causes of respiratory morbidity and mortality are tobacco smoking, infection, and air pollution. this review aims to summarize current respiratory health issues in the region including smoking-related diseases especially copd, lung cancer and infectious problems such as pandemic influenza, th ...201120920119
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
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
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
Biochemical and structural insights into the mechanisms of SARS coronavirus RNA ribose 2'-O-methylation by nsp16/nsp10 protein complex.The 5'-cap structure is a distinct feature of eukaryotic mRNAs, and eukaryotic viruses generally modify the 5'-end of viral RNAs to mimic cellular mRNA structure, which is important for RNA stability, protein translation and viral immune escape. SARS coronavirus (SARS-CoV) encodes two S-adenosyl-L-methionine (SAM)-dependent methyltransferases (MTase) which sequentially methylate the RNA cap at guanosine-N7 and ribose 2'-O positions, catalyzed by nsp14 N7-MTase and nsp16 2'-O-MTase, respectively. ...201122022266
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
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
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
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
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
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
a real-time pcr assay for bat sars-like coronavirus detection and its application to italian greater horseshoe bat faecal sample surveys.bats are source of coronaviruses closely related to the severe acute respiratory syndrome (sars) virus. numerous studies have been carried out to identify new bat viruses related to sars-coronavirus (bat-sars-like covs) using a reverse-transcribed-polymerase chain reaction assay. however, a qualitative pcr could underestimate the prevalence of infection, affecting the epidemiological evaluation of bats in viral ecology. in this work an sybr green-real time pcr assay was developed for diagnosing ...201122654650
a real-time pcr assay for bat sars-like coronavirus detection and its application to italian greater horseshoe bat faecal sample surveys.bats are source of coronaviruses closely related to the severe acute respiratory syndrome (sars) virus. numerous studies have been carried out to identify new bat viruses related to sars-coronavirus (bat-sars-like covs) using a reverse-transcribed-polymerase chain reaction assay. however, a qualitative pcr could underestimate the prevalence of infection, affecting the epidemiological evaluation of bats in viral ecology. in this work an sybr green-real time pcr assay was developed for diagnosing ...201122654650
stability of bovine coronavirus on lettuce surfaces under household refrigeration conditions.fecal suspensions with an aerosol route of transmission were responsible for a cluster of severe acute respiratory syndrome (sars) cases in 2003 in hong kong. based on that event, the world health organization recommended that research be implemented to define modes of transmission of sars coronavirus through sewage, feces, food and water. environmental studies have shown that animal coronaviruses remain infectious in water and sewage for up to a year depending on the temperature and humidity. i ...201122265299
characterization of germline antibody libraries from human umbilical cord blood and selection of monoclonal antibodies to viral envelope glycoproteins: implications for mechanisms of immune evasion and design of vaccine immunogens.we have previously observed that all known hiv-1 broadly neutralizing antibodies (bnabs) are highly divergent from germline antibodies in contrast to bnabs against hendra virus, nipah virus and sars coronavirus (sars cov). we have hypothesized that because the germline antibodies are so different from the mature hiv-1-specific bnabs they may not bind the epitopes of the mature antibodies and provided the first evidence to support this hypothesis by using individual putative germline-like predece ...201122226962
SARS coronavirus nucleocapsid protein monoclonal antibodies developed using a prokaryotic expressed protein.Immunological detection of viruses and their components using monoclonal antibodies (MAbs) is a powerful diagnostic method. Here we report a detailed method for the establishment of MAbs against severe acute respiratory syndrome coronavirus (SARS-CoV). To express and purify the nucleocapsid protein (N protein) of SARS-CoV and generate MAbs against the N protein, gene encoding N protein was separated into two parts according to the prediction of epitopes and cloned into pET32a(+), respectively. E ...201122008077
integrative deep sequencing of the mouse lung transcriptome reveals differential expression of diverse classes of small rnas in response to respiratory virus infection.we previously reported widespread differential expression of long non-protein-coding rnas (ncrnas) in response to virus infection. here, we expanded the study through small rna transcriptome sequencing analysis of the host response to both severe acute respiratory syndrome coronavirus (sars-cov) and influenza virus infections across four founder mouse strains of the collaborative cross, a recombinant inbred mouse resource for mapping complex traits. we observed differential expression of over 20 ...201122086488
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
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
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
human-leukocyte antigen class i cw 1502 and class ii dr 0301 genotypes are associated with resistance to severe acute respiratory syndrome (sars) infection.one-hundred and thirty confirmed cases of severe acute respiratory syndrome (sars) were recruited to evaluate their anti-sars-coronavirus (cov) antibody status and human leukocyte antigen (hla) types in september 2006, 3 y after the sars outbreaks in taiwan. western blot assay showed that 6.9% of participants still had anti-spike and anti-nucleocapside antibodies. a case-control study of the association of hla with sars revealed that the hla-cw1502 and dr0301 alleles conferred resistance against ...201121958371
bat severe acute respiratory syndrome-like coronavirus orf3b homologues display different interferon antagonist activities.the orf3b protein of severe acute respiratory syndrome coronavirus (sars-cov) has a nuclear localization signal (nls) at its c terminus and antagonizes interferon (ifn) function by modulating the activity of ifn regulatory factor 3 (irf3). sars-like coronaviruses (sl-covs) found in bats share an identical genome organization and high sequence identity for most of their gene products. in this study, orf3b homologues were identified from three bat sl-cov strains. these orf3b homologues were c-term ...201122012463
Severe acute respiratory syndrome coronavirus envelope protein regulates cell stress response and apoptosis.Severe acute respiratory syndrome virus (SARS-CoV) that lacks the envelope (E) gene (rSARS-CoV-?E) is attenuated in vivo. To identify factors that contribute to rSARS-CoV-?E attenuation, gene expression in cells infected by SARS-CoV with or without E gene was compared. Twenty-five stress response genes were preferentially upregulated during infection in the absence of the E gene. In addition, genes involved in signal transduction, transcription, cell metabolism, immunoregulation, inflammation, a ...201122028656
a putative diacidic motif in the sars-cov orf6 protein influences its subcellular localization and suppression of expression of co-transfected expression constructs.abstract:201122026976
Molecular diagnosis of respiratory virus infections.The appearance of eight new respiratory viruses, including the SARS coronavirus in 2003 and swine-origin influenza A/H1N1 in 2009, in the human population in the past nine years has tested the ability of virology laboratories to develop diagnostic tests to identify these viruses. Nucleic acid based amplification tests (NATs) for respiratory viruses were first introduced two decades ago and today are utilized for the detection of both conventional and emerging viruses. These tests are more sensit ...201122185616
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
The SARS-coronavirus-host interactome: identification of cyclophilins as target for pan-coronavirus inhibitors.Coronaviruses (CoVs) are important human and animal pathogens that induce fatal respiratory, gastrointestinal and neurological disease. The outbreak of the severe acute respiratory syndrome (SARS) in 2002/2003 has demonstrated human vulnerability to (Coronavirus) CoV epidemics. Neither vaccines nor therapeutics are available against human and animal CoVs. Knowledge of host cell proteins that take part in pivotal virus-host interactions could define broad-spectrum antiviral targets. In this study ...201122046132
comparison of sars and nl63 papain-like protease binding sites and binding site dynamics: inhibitor design implications.the human severe acute respiratory syndrome coronavirus (sars-cov) and the nl63 coronaviruses are human respiratory pathogens for which no effective antiviral treatment exists. the papain-like cysteine proteases encoded by the coronavirus (sars-cov: plpro; nl63: plp1 and plp2) represent potential targets for antiviral drug development. three recent inhibitor-bound plpro structures highlight the role of an extremely flexible six-residue loop in inhibitor binding. the high binding site plasticity ...201122004941
a chemokine gene expression signature derived from meta-analysis predicts the pathogenicity of viral respiratory infections.abstract: background: during respiratory viral infections host injury occurs due in part to inappropriate host responses. in this study we sought to uncover the host transcriptional responses underlying differences between high- and low-pathogenic infections. results: from a compendium of 12 studies that included responses to influenza a subtype h5n1, reconstructed 1918 influenza a virus, and sars coronavirus, we used meta-analysis to derive multiple gene expression signatures. we compared thes ...201122189154
age-related increases in pgd(2) expression impair respiratory dc migration, resulting in diminished t cell responses upon respiratory virus infection in mice.the morbidity and mortality associated with respiratory virus infection is felt most keenly among the elderly. t cells are necessary for viral clearance, and many age-dependent intrinsic t cell defects have been documented. however, the development of robust t cell responses in the lung also requires respiratory dcs (rdcs), which must process antigen and migrate to draining lns (dlns), and little is known about age-related defects in these t cell-extrinsic functions. here, we show that increases ...201122105170
cleavage and activation of the severe acute respiratory syndrome coronavirus spike protein by human airway trypsin-like protease.the highly pathogenic severe acute respiratory syndrome coronavirus (sars-cov) poses a constant threat to human health. the viral spike protein (sars-s) mediates host cell entry and is a potential target for antiviral intervention. activation of sars-s by host cell proteases is essential for sars-cov infectivity but remains incompletely understood. here, we analyzed the role of the type ii transmembrane serine proteases (ttsps) human airway trypsin-like protease (hat) and transmembrane protease, ...201121994442
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
profiling of substrate specificities of 3c-like proteases from group 1, 2a, 2b, and 3 coronaviruses.coronaviruses (covs) can be classified into alphacoronavirus (group 1), betacoronavirus (group 2), and gammacoronavirus (group 3) based on diversity of the protein sequences. their 3c-like protease (3cl(pro)), which catalyzes the proteolytic processing of the polyproteins for viral replication, is a potential target for anti-coronaviral infection.201122073294
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
Ultrastructural characterization of arterivirus replication structures: Reshaping the endoplasmic reticulum to accommodate viral RNA synthesis.Virus-induced membrane structures support the assembly and function of positive-stranded RNA virus replication complexes. The replicase proteins of arteriviruses are associated with double-membrane vesicles (DMVs), which were previously proposed to derive from endoplasmic reticulum (ER). Using electron tomography, we performed an in-depth ultrastructural analysis of cells infected with the prototypic arterivirus equine arteritis virus (EAV). We established that the outer membranes of EAV-induced ...201122190716
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
SARS Coronavirus nsp1 Protein Induces Template-Dependent Endonucleolytic Cleavage of mRNAs: Viral mRNAs Are Resistant to nsp1-Induced RNA Cleavage.SARS coronavirus (SCoV) nonstructural protein (nsp) 1, a potent inhibitor of host gene expression, possesses a unique mode of action: it binds to 40S ribosomes to inactivate their translation functions and induces host mRNA degradation. Our previous study demonstrated that nsp1 induces RNA modification near the 5'-end of a reporter mRNA having a short 5' untranslated region and RNA cleavage in the encephalomyocarditis virus internal ribosome entry site (IRES) region of a dicistronic RNA template ...201122174690
[Advantages and prospects of the use of genetic vaccines for the protection from dangerous and socially significant infections].High frequency of epidemiological threats (H5N1 influenza, SARS, etc.) in modern world calls for the development of new flexible technologies for manufacturing efficacious vaccines and rapid reorientation of their production as appropriate. Genetic vaccination is one of such technologies aimed at prophylaxis of dangerous and socially significant infections. The technology is based on administration of one or several functionally active genes encoding for antigens of pathogens which induces forma ...201122168038
quantitative and sensitive detection of sars coronavirus nucleocapsid protein using quantum dots-conjugated rna aptamer on chip.background: globally, severe acute respiratory syndrome coronavirus (sars-cov) is a newly emerging virus that causes sars with high mortality rate in infected people. the nucleocapsid (n) protein of the severe acute respiratory syndrome (sars)-associated coronavirus (sars-cov) is an important antigen for the early diagnosis of sars and the detection of diseases. here, a new quantum dots (qds)-conjugated rna aptamer with high sensitivity and rapidity is proposed for the detection of sars-cov n pr ...201132336860
the effects of temperature and relative humidity on the viability of the sars coronavirus.the main route of transmission of sars cov infection is presumed to be respiratory droplets. however the virus is also detectable in other body fluids and excreta. the stability of the virus at different temperatures and relative humidity on smooth surfaces were studied. the dried virus on smooth surfaces retained its viability for over 5 days at temperatures of 22-25°c and relative humidity of 40-50%, that is, typical air-conditioned environments. however, virus viability was rapidly lost (>3 l ...201122312351
pathogenesis of sars coronavirus infection using human lung epithelial cells: an in vitro model. 201122147357
identification of t-cell epitopes of sars-coronavirus for development of peptide-based vaccines and cellular immunity assessment methods. 201122147356
unconventional use of lc3 by coronaviruses through the alleged subversion of the erad tuning pathway.pathogens of bacterial and viral origin hijack pathways operating in eukaryotic cells in many ways in order to gain access into the host, to establish themselves and to eventually produce their progeny. the detailed molecular characterization of the subversion mechanisms devised by pathogens to infect host cells is crucial to generate targets for therapeutic intervention. here we review recent data indicating that coronaviruses probably co-opt membranous carriers derived from the endoplasmic ret ...201121994798
emerging zoonotic viruses: new lessons on receptor and entry mechanisms.viruses enter the host cell by binding cellular receptors that allow appropriate delivery of the viral genome. although the horizontal propagation of viruses feeds the continuous emergence of novel pathogenic viruses, the genetic variation of cellular receptors can represent a challenging barrier. the sars coronavirus, henipaviruses and filoviruses are zoonotic rna viruses that use bats as their reservoir. their lethality for man has fostered extensive research both on the cellular receptors the ...201122440564
evidence for ace2-utilizing coronaviruses (covs) related to severe acute respiratory syndrome cov in bats.in 2002, severe acute respiratory syndrome (sars)-coronavirus (cov) appeared as a novel human virus with high similarity to bat coronaviruses. however, while sars-cov uses the human angiotensin-converting enzyme 2 (ace2) receptor for cellular entry, no coronavirus isolated from bats appears to use ace2. here we show that signatures of recurrent positive selection in the bat ace2 gene map almost perfectly to known sars-cov interaction surfaces. our data indicate that ace2 utilization preceded the ...201222438550
differential domain structure stability of the severe acute respiratory syndrome coronavirus papain-like protease.papain-like protease (plpro) from severe acute respiratory syndrome (sars) coronavirus is one of the two proteases involved in the proteolytic processing of the virion polyproteins. in addition, plpro shows significant in vitro deubiquitinating and de-isgylating activities. all these findings demonstrated the multifunctional nature of the plpro. here we report the sensitivity of plpro to denaturant urea. an increase in urea concentration induced a reversible biphasic unfolding of the enzyme. dif ...201222391227
the sars-like coronaviruses: the role of bats and evolutionary relationships with sars coronavirus.bats represent an order of great evolutionary success, with elevated geographical diffusion and species diversity. this order harbors viruses of high variability which have a great possibility of acquiring the capacity of infecting other animals,including humans. bats are the natural reservoir for several viruses genetically closely related to the sarscoronavirus which is the etiological agent of severe acute respiratory syndrome (sars), a human epidemic which emerged in china in 2002-2003. in t ...201222378548
flavonoid-mediated inhibition of sars coronavirus 3c-like protease expressed in pichia pastoris.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. recombinant 3cl(pro) was expressed in pichia pastoris gs115 as a 42 kda protein that displayed a k ( m ) of 15 ± 2 μm with dabcyl-ktsavlqsgfrkme-edans as substrate. purified 3cl(pro) was used for inhibition and kinetic assays with seven flavonoid compounds. the ic(50) of six flavonoid compounds were 47-381 μm. quercetin, epigallo ...201222350287
primary severe acute respiratory syndrome coronavirus infection limits replication but not lung inflammation upon homologous rechallenge.our knowledge regarding immune-protective and immunopathogenic events in severe acute respiratory syndrome coronavirus (sars-cov) infection is limited, and little is known about the dynamics of the immune response at the primary site of disease. here, an african green monkey (agm) model was used to elucidate immune mechanisms that facilitate viral clearance but may also contribute to persistent lung inflammation following sars-cov infection. during primary infection, sars-cov replicated in the a ...201222345460
roadmap to developing a recombinant coronavirus s protein receptor-binding domain vaccine for severe acute respiratory syndrome.a subunit vaccine, rbd-s, is under development to prevent severe acute respiratory syndrome (sars) caused by sars coronavirus (sars-cov), which is classified by the us nih as a category c pathogen. this vaccine is comprised of a recombinant receptor-binding domain (rbd) of the sars-cov spike (s) protein and formulated on alum, together with a synthetic glucopyranosyl lipid a. the vaccine would induce neutralizing antibodies without causing th2-type immunopathology. vaccine development is being l ...201223252385
human coronavirus emc does not require the sars-coronavirus receptor and maintains broad replicative capability in mammalian cell lines.a new human coronavirus (hcov-emc) has emerged very recently in the middle east. the clinical presentation resembled that of the severe acute respiratory syndrome (sars) as encountered during the epidemic in 2002/2003. in both cases, acute renal failure was observed in humans. hcov-emc is a member of the same virus genus as sars-cov but constitutes a sister species. here we investigated whether it might utilize angiotensin-converting enzyme 2 (ace2), the sars-cov receptor. knowledge of the recep ...201223232719
the role of severe acute respiratory syndrome (sars)-coronavirus accessory proteins in virus pathogenesis.a respiratory disease caused by a novel coronavirus, termed the severe acute respiratory syndrome coronavirus (sars-cov), was first reported in china in late 2002. the subsequent efficient human-to-human transmission of this virus eventually affected more than 30 countries worldwide, resulting in a mortality rate of ~10% of infected individuals. the spread of the virus was ultimately controlled by isolation of infected individuals and there has been no infections reported since april 2004. ...201223202509
a framework for the study of zoonotic disease emergence and its drivers: spillover of bat pathogens as a case study.many serious emerging zoonotic infections have recently arisen from bats, including ebola, marburg, sars-coronavirus, hendra, nipah, and a number of rabies and rabies-related viruses, consistent with the overall observation that wildlife are an important source of emerging zoonoses for the human population. mechanisms underlying the recognized association between ecosystem health and human health remain poorly understood and responding appropriately to the ecological, social and economic conditi ...201222966143
correlation between tgf-β1 expression and proteomic profiling induced by severe acute respiratory syndrome coronavirus papain-like protease.severe acute respiratory syndrome (sars) coronavirus (sars-cov) papain-like protease (plpro), a deubiquitinating enzyme, demonstrates inactivation of interferon (ifn) regulatory factor 3 and nf-κb, reduction of ifn induction, and suppression of type i ifn signaling pathway. this study investigates cytokine expression and proteomic change induced by sars-cov plpro in human promonocyte cells. plpro significantly increased tgf-β1 mrna expression (greater than fourfold) and protein production (great ...201222936401
development of chemical inhibitors of the sars coronavirus: viral helicase as a potential target.severe acute respiratory syndrome (sars) was the first pandemic in the 21st century to claim more than 700 lives worldwide. however, effective anti-sars vaccines or medications are currently unavailable despite being desperately needed to adequately prepare for a possible sars outbreak. sars is caused by a novel coronavirus, and one of its components, a viral helicase, is emerging as a promising target for the development of chemical sars inhibitors. in the following review, we describe the char ...201222935448
understanding the t cell immune response in sars coronavirus infection.the severe acute respiratory syndrome (sars) epidemic started in late 2002 and swiftly spread across 5 continents with a mortality rate of around 10%. although the epidemic was eventually controlled through the implementation of strict quarantine measures, there continues a need to investigate the sars coronavirus (sars-cov) and develop interventions should it re-emerge. numerous studies have shown that neutralizing antibodies against the virus can be found in patients infected with sars-cov wit ...201226038429
role of dendritic cells in sars coronavirus infection. 201222865220
impact of sars-coronavirus-encoded proteins on cellular signalling pathways and cytokine/chemokine gene expression. 201222865217
origin, diversity, and maturation of human antiviral antibodies analyzed by high-throughput sequencing.our understanding of how antibodies are generated and function could help develop effective vaccines and antibody-based therapeutics against viruses such as hiv-1, sars coronavirus (sars cov), and hendra and nipah viruses (henipaviruses). although broadly neutralizing antibodies (bnabs) against the hiv-1 were observed in patients, elicitation of such bnabs remains a major challenge when compared to other viral targets. we previously hypothesized that hiv-1 could have evolved a strategy to evade ...201222876240
severe acute respiratory syndrome coronavirus nsp1 facilitates efficient propagation in cells through a specific translational shutoff of host mrna.severe acute respiratory syndrome (sars) coronavirus (scov) is an enveloped virus containing a single-stranded, positive-sense rna genome. nine mrnas carrying a set of common 5' and 3' untranslated regions (utr) are synthesized from the incoming viral genomic rna in cells infected with scov. a nonstructural scov nsp1 protein causes a severe translational shutoff by binding to the 40s ribosomal subunits. the nsp1-40s ribosome complex further induces an endonucleolytic cleavage near the 5'utr of h ...201222855488
biochemical characterization of a recombinant sars coronavirus nsp12 rna-dependent rna polymerase capable of copying viral rna templates.the severe acute respiratory syndrome coronavirus (sars-cov) rna genome is replicated by a virus-encoded rna replicase, the key component of which is the nonstructural protein 12 (nsp12). in this report, we describe the biochemical properties of a full-length recombinant sars-cov nsp12 rna-dependent rna polymerase (rdrp) capable of copying viral rna templates. the purified sars-cov nsp12 showed both primer-dependent and primer-independent rna synthesis activities using homopolymeric rna template ...201222791111
short peptides derived from the interaction domain of sars coronavirus nonstructural protein nsp10 can suppress the 2'-o-methyltransferase activity of nsp10/nsp16 complex.coronaviruses are the etiological agents of respiratory and enteric diseases in humans and livestock, exemplified by the life-threatening severe acute respiratory syndrome (sars) caused by sars coronavirus (sars-cov). however, effective means for combating coronaviruses are still lacking. the interaction between nonstructural protein (nsp) 10 and nsp16 has been demonstrated and the crystal structure of sars-cov nsp16/10 complex has been revealed. as nsp10 acts as an essential trigger to activate ...201222659295
a facile inhibitor screening of sars coronavirus n protein using nanoparticle-based rna oligonucleotide.hundreds of million people worldwide have been infected with severe acute respiratory syndrome (sars), and the rate of global death from sars has remarkably increased. hence, the development of efficient drug treatments for the biological effects of sars is highly needed. we have previously shown that quantum dots (qds)-conjugated rna oligonucleotide is sensitive to the specific recognition of the sars-associated coronavirus (sars-cov) nucleocapsid (n) protein. in this study, we found that a des ...201222619553
sars coronavirus pathogenesis: host innate immune responses and viral antagonism of interferon.sars-cov is a pathogenic coronavirus that emerged from a zoonotic reservoir, leading to global dissemination of the virus. the association sars-cov with aberrant cytokine, chemokine, and interferon stimulated gene (isg) responses in patients provided evidence that sars-cov pathogenesis is at least partially controlled by innate immune signaling. utilizing models for sars-cov infection, key components of innate immune signaling pathways have been identified as protective factors against sars-cov ...201222572391
influenza and sars-coronavirus activating proteases tmprss2 and hat are expressed at multiple sites in human respiratory and gastrointestinal tracts.the type ii transmembrane serine proteases tmprss2 and hat activate influenza viruses and the sars-coronavirus (tmprss2) in cell culture and may play an important role in viral spread and pathogenesis in the infected host. however, it is at present largely unclear to what extent these proteases are expressed in viral target cells in human tissues. here, we show that both hat and tmprss2 are coexpressed with 2,6-linked sialic acids, the major receptor determinant of human influenza viruses, throu ...201222558251
comparison of trends in the quantity and variety of science citation index (sci) literature on human pathogens between china and the united states.the proportion of pathogenic microorganisms in the microbial world is relatively small, while their threat to human health, economic development and social stability is severe. the quantity and variation of science citation index (sci) literature related to pathogenic microorganisms may reflect the level of relevant research and the degree of attention. here we compared trends in the quantity and variety of sci literature relating to certain important pathogenic microorganisms published by scien ...201232214557
emerging viral infections in india.despite an elaborate armamentarium to tackle microbes, emerging infectious diseases remain a crucial global challenge. emerging infections can be defined as "infections that have newly appeared in a population or have existed previously but are rapidly increasing in incidence or geographic range." several factors like increase in international travel and trade, human encroachment on wild-life habitats, changes in agricultural practices and wild-life trade have contributed to the emergence of pat ...201232226201
sars coronavirus 3b accessory protein modulates transcriptional activity of runx1b.the causative agent of severe acute respiratory syndrome, sars coronavirus (sars-cov) genome encodes several unique group specific accessory proteins with unknown functions. among them, accessory protein 3b (also known as orf4) was lately identified as one of the viral interferon antagonist. recently our lab uncovered a new role for 3b in upregulation of ap-1 transcriptional activity and its downstream genes. thus, we believe that 3b might play an important role in sars-cov pathogenesis and ther ...201222253733
phosphatidylinositol 4-kinase iii beta is required for severe acute respiratory syndrome coronavirus spike-mediated cell entry.phosphatidylinositol kinases (pi kinases) play an important role in the life cycle of several viruses after infection. using gene knockdown technology, we demonstrate that phosphatidylinositol 4-kinase iii beta (pi4kb) is required for cellular entry by pseudoviruses bearing the sars-cov spike protein and that the cell entry mediated by sars-cov s is strongly inhibited by knockdown of pi4kb. consistent with this observation, pharmacological inhibitors of pi4kb blocked entry of sars pseudovirions. ...201222253445
Molecular determinants of severe acute respiratory syndrome coronavirus pathogenesis and virulence in young and aged mouse models of human disease.SARS coronavirus (SARS-CoV) causes severe acute respiratory tract disease characterized by diffuse alveolar damage and hyaline membrane formation. This pathology often progresses to acute respiratory distress (such as acute respiratory distress syndrome [ARDS]) and atypical pneumonia in humans, with characteristic age-related mortality rates approaching 50% or more in immunosenescent populations. The molecular basis for the extreme virulence of SARS-CoV remains elusive. Since young and aged (1-y ...201222072787
[highly contagious diseases with human-to-human transmission].highly contagious diseases are caused by various biological agents that pose a risk to individuals and may have a potential for public health impact. they result in high mortality and morbidity rates, might cause public panic and therefore require special measures. the pathogens that can be easily disseminated or transmitted from person to person are the riskiest for clinicians (ebola virus, marburg virus, lassa virus, crimean-congo hemorrhagic fever virus, variola major, sars virus and yersinia ...201223386507
bats and their virome: an important source of emerging viruses capable of infecting humans.bats are being increasingly recognized as an important reservoir of zoonotic viruses of different families, including sars coronavirus, nipah virus, hendra virus and ebola virus. several recent studies hypothesized that bats, an ancient group of flying mammals, are the major reservoir of several important rna virus families from which other mammalian viruses of livestock and humans were derived. although this hypothesis needs further investigation, the premise that bats carry a large number of v ...201223265969
two years after pandemic influenza a/2009/h1n1: what have we learned?the world had been anticipating another influenza pandemic since the last one in 1968. the pandemic influenza a h1n1 2009 virus (a/2009/h1n1) finally arrived, causing the first pandemic influenza of the new millennium, which has affected over 214 countries and caused over 18,449 deaths. because of the persistent threat from the a/h5n1 virus since 1997 and the outbreak of the severe acute respiratory syndrome (sars) coronavirus in 2003, medical and scientific communities have been more prepared i ...201222491771
θ-defensins: cyclic peptides with endless potential.θ-defensins, the only cyclic peptides of animal origin, have been isolated from the leukocytes of rhesus macaques and baboons. their biogenesis is unusual because each peptide is an 18-residue chimera formed by the head-to-tail splicing of nonapeptides derived from two separate precursors. θ-defensins have multiple arginines and a ladder-like tridisulfide array spanning their two antiparallel β-strands. human θ-defensin genes contain a premature stop codon that prevents effective translation of ...201222700960
lack of innate interferon responses during sars coronavirus infection in a vaccination and reinfection ferret model.in terms of its highly pathogenic nature, there remains a significant need to further define the immune pathology of sars-coronavirus (sars-cov) infection, as well as identify correlates of immunity to help develop vaccines for severe coronaviral infections. here we use a sars-cov infection-reinfection ferret model and a functional genomics approach to gain insight into sars immunopathogenesis and to identify correlates of immune protection during sars-cov-challenge in ferrets previously infecte ...201223029269
immunization with sars coronavirus vaccines leads to pulmonary immunopathology on challenge with the sars virus.severe acute respiratory syndrome (sars) emerged in china in 2002 and spread to other countries before brought under control. because of a concern for reemergence or a deliberate release of the sars coronavirus, vaccine development was initiated. evaluations of an inactivated whole virus vaccine in ferrets and nonhuman primates and a virus-like-particle vaccine in mice induced protection against infection but challenged animals exhibited an immunopathologic-type lung disease.201222536382
development of novel entry inhibitors targeting emerging viruses.emerging viral diseases pose a unique risk to public health, and thus there is a need to develop therapies. a current focus of funding agencies, and hence research, is the development of broad-spectrum antivirals, and in particular, those targeting common cellular pathways. the scope of this article is to review screening strategies and recent advances in this area, with a particular emphasis on antivirals targeting the step of viral entry for emerging lipid-enveloped viruses such as ebola virus ...201223199399
severe acute respiratory syndrome coronavirus replication inhibitor that interferes with the nucleic acid unwinding of the viral helicase.severe acute respiratory syndrome (sars) is a highly contagious disease, caused by sars coronavirus (sars-cov), for which there are no approved treatments. we report the discovery of a potent inhibitor of sars-cov that blocks replication by inhibiting the unwinding activity of the sars-cov helicase (nsp13). we used a förster resonance energy transfer (fret)-based helicase assay to screen the maybridge hitfinder chemical library. we identified and validated a compound (ssya10-001) that specifical ...201222733076
severe acute respiratory syndrome coronavirus protein nsp1 is a novel eukaryotic translation inhibitor that represses multiple steps of translation initiation.severe acute respiratory syndrome (sars) coronavirus nonstructural protein 1 (nsp1) binds to the 40s ribosomal subunit and inhibits translation, and it also induces a template-dependent endonucleolytic cleavage of host mrnas. nsp1 inhibits the translation of cap-dependent and internal ribosome entry site (ires)-driven mrnas, including sars coronavirus mrnas, hepatitis c virus (hcv), and cricket paralysis virus (crpv) ires-driven mrnas that are resistant to nsp1-induced rna cleavage. we used an n ...201223035226
identification of myricetin and scutellarein as novel chemical inhibitors of the sars coronavirus helicase, nsp13.severe acute respiratory syndrome (sars) is an infectious disease with a strong potential for transmission upon close personal contact and is caused by the sars-coronavirus (cov). however, there are no natural or synthetic compounds currently available that can inhibit sars-cov. we examined the inhibitory effects of 64 purified natural compounds against the activity of sars helicase, nsp13, and the hepatitis c virus (hcv) helicase, ns3h, by conducting fluorescence resonance energy transfer (fret ...201222578462
a hexapeptide of the receptor-binding domain of sars corona virus spike protein blocks viral entry into host cells via the human receptor ace2.in vitro infection of vero e6 cells by sars coronavirus (sars-cov) is blocked by hexapeptide tyr-lys-tyr-arg-tyr-leu. the peptide also inhibits proliferation of coronavirus nl63. on human cells both viruses utilize angiotensin-converting enzyme 2 (ace2) as entry receptor. blocking the viral entry is specific as alpha virus sindbis shows no reduction in infectivity. peptide (438)ykyryl(443) is part of the receptor-binding domain (rbd) of the spike protein of sars-cov. peptide libraries were scree ...201222265858
binding of the 5'-untranslated region of coronavirus rna to zinc finger cchc-type and rna-binding motif 1 enhances viral replication and transcription.coronaviruses rna synthesis occurs in the cytoplasm and is regulated by host cell proteins. in a screen based on a yeast three-hybrid system using the 5'-untranslated region (5'-utr) of sars coronavirus (sars-cov) rna as bait against a human cdna library derived from hela cells, we found a positive candidate cellular protein, zinc finger cchc-type and rna-binding motif 1 (madp1), to be able to interact with this region of the sars-cov genome. this interaction was subsequently confirmed in corona ...201222362731
identification of common biological pathways and drug targets across multiple respiratory viruses based on human host gene expression analysis.pandemic and seasonal respiratory viruses are a major global health concern. given the genetic diversity of respiratory viruses and the emergence of drug resistant strains, the targeted disruption of human host-virus interactions is a potential therapeutic strategy for treating multi-viral infections. the availability of large-scale genomic datasets focused on host-pathogen interactions can be used to discover novel drug targets as well as potential opportunities for drug repositioning.201222432004
ezrin interacts with the sars coronavirus spike protein and restrains infection at the entry stage.entry of severe acute respiratory syndrome coronavirus (sars-cov) and its envelope fusion with host cell membrane are controlled by a series of complex molecular mechanisms, largely dependent on the viral envelope glycoprotein spike (s). there are still many unknowns on the implication of cellular factors that regulate the entry process.201223185364
chinese hamster ovary cell lines selected for resistance to ebolavirus glycoprotein mediated infection are defective for npc1 expression.ebolavirus causes severe hemorrhagic fever in humans and non-human primates. entry of ebolavirus is mediated by the viral glycoprotein, gp; however, the required host factors have not been fully elucidated. a screen utilizing a recombinant vesicular stomatitis virus (vsv) encoding zaire ebolavirus gp identified four chinese hamster ovary (cho) cell lines resistant to gp-mediated viral entry. susceptibility to vectors carrying sars coronavirus s or vsv-g glycoproteins suggests that endocytic and ...201222726751
chinese hamster ovary cell lines selected for resistance to ebolavirus glycoprotein mediated infection are defective for npc1 expression.ebolavirus causes severe hemorrhagic fever in humans and non-human primates. entry of ebolavirus is mediated by the viral glycoprotein, gp; however, the required host factors have not been fully elucidated. a screen utilizing a recombinant vesicular stomatitis virus (vsv) encoding zaire ebolavirus gp identified four chinese hamster ovary (cho) cell lines resistant to gp-mediated viral entry. susceptibility to vectors carrying sars coronavirus s or vsv-g glycoproteins suggests that endocytic and ...201222726751
is the discovery of the novel human betacoronavirus 2c emc/2012 (hcov-emc) the beginning of another sars-like pandemic?fouchier et al. reported the isolation and genome sequencing of a novel coronavirus tentatively named "human betacoronavirus 2c emc/2012 (hcov-emc)" from a saudi patient presenting with pneumonia and renal failure in june 2012. genome sequencing showed that this virus belongs to the group c species of the genus betacoronavirus and phylogenetically related to the bat coronaviruses hku4 and hku5 previously found in lesser bamboo bat and japanese pipistrelle bat of hong kong respectively. another p ...201223072791
is the discovery of the novel human betacoronavirus 2c emc/2012 (hcov-emc) the beginning of another sars-like pandemic?fouchier et al. reported the isolation and genome sequencing of a novel coronavirus tentatively named "human betacoronavirus 2c emc/2012 (hcov-emc)" from a saudi patient presenting with pneumonia and renal failure in june 2012. genome sequencing showed that this virus belongs to the group c species of the genus betacoronavirus and phylogenetically related to the bat coronaviruses hku4 and hku5 previously found in lesser bamboo bat and japanese pipistrelle bat of hong kong respectively. another p ...201223072791
In vitro anti-hepatitis B and SARS virus activities of a titanium-substituted-heteropolytungstate.A structural determined heteropolytungstate, [K(4)(H(2)O)(8)Cl][K(4)(H(2)O)(4)PTi(2)W(10)O(40)]·NH(2)OH 1, has been synthesized and evaluated for in vitro antiviral activities against hepatitis B (HBV) and SARS virus. The identity and high purity of compound 1 were confirmed by elemental analysis, NMR, IR analysis and single-crystal X-ray diffraction. The compound 1, evaluated in HepG 2.2.15 cells expressing permanently HBV, significantly reduced the levels of HBV antigens and HBV DNA in a dose- ...201222127069
metagenomic study of the viruses of african straw-coloured fruit bats: detection of a chiropteran poxvirus and isolation of a novel adenovirus.viral emergence as a result of zoonotic transmission constitutes a continuous public health threat. emerging viruses such as sars coronavirus, hantaviruses and henipaviruses have wildlife reservoirs. characterising the viruses of candidate reservoir species in geographical hot spots for viral emergence is a sensible approach to develop tools to predict, prevent, or contain emergence events. here, we explore the viruses of eidolon helvum, an old world fruit bat species widely distributed in afric ...201323562481
metagenomic study of the viruses of african straw-coloured fruit bats: detection of a chiropteran poxvirus and isolation of a novel adenovirus.viral emergence as a result of zoonotic transmission constitutes a continuous public health threat. emerging viruses such as sars coronavirus, hantaviruses and henipaviruses have wildlife reservoirs. characterising the viruses of candidate reservoir species in geographical hot spots for viral emergence is a sensible approach to develop tools to predict, prevent, or contain emergence events. here, we explore the viruses of eidolon helvum, an old world fruit bat species widely distributed in afric ...201323562481
in-vitro renal epithelial cell infection reveals a viral kidney tropism as a potential mechanism for acute renal failure during middle east respiratory syndrome (mers) coronavirus infection.the middle east respiratory syndrome coronavirus (mers-cov) causes symptoms similar to severe acute respiratory syndrome coronavirus (sars-cov), yet involving an additional component of acute renal failure (arf) according to several published case reports. impairment of the kidney is not typically seen in coronavirus infections. the role of kidney infection in mers is not understood.201324364985
serological evidence of toxoplasma gondii infection in five species of bats in china.toxoplasma gondii is an obligate intracellular protozoan parasite that can infect almost all warm-blooded animals and humans with a worldwide distribution. bats are reservoirs for an increasing number of emerging zoonotic viruses, such as henipaviruses and severe acute respiratory syndrome coronavirus (sars-cov). however, little is known of t. gondii infection in bats. the objective of the present study was to determine the seroprevalence of t. gondii infection in bats in china. a total of 217 s ...201323473226
synthesis and biological activity evaluation of 5-pyrazoline substituted 4-thiazolidinones.a series of novel 5-pyrazoline substituted 4-thiazolidinones have been synthesized. target compounds were evaluated for their anticancer activity in vitro within dtp nci protocol. among the tested compounds, the derivatives 4d and 4f were found to be the most active, which demonstrated certain sensitivity profile toward the leukemia subpanel cell lines with gi₅₀ value ranges of 2.12-4.58 μm (4d) and 1.64-3.20 μm (4f). the screening of antitrypanosomal and antiviral activities of 5-(3-naphthalen- ...201323811085
complete protection against severe acute respiratory syndrome coronavirus-mediated lethal respiratory disease in aged mice by immunization with a mouse-adapted virus lacking e protein.zoonotic coronaviruses, including the one that caused severe acute respiratory syndrome (sars), cause significant morbidity and mortality in humans. no specific therapy for any human coronavirus is available, making vaccine development critical for protection against these viruses. we previously showed that recombinant sars coronavirus (sars-cov) (urbani strain based) lacking envelope (e) protein expression (ru-δe) provided good but not perfect protection in young mice against challenge with vir ...201323576515
regulation of programmed ribosomal frameshifting by co-translational refolding rna hairpins.rna structures are unwound for decoding. in the process, they can pause the elongating ribosome for regulation. an example is the stimulation of -1 programmed ribosomal frameshifting, leading to 3' direction slippage of the reading-frame during elongation, by specific pseudoknot stimulators downstream of the frameshifting site. by investigating a recently identified regulatory element upstream of the sars coronavirus (sars-cov) -1 frameshifting site, it is shown that a minimal functional element ...201323638024
feature selection methods for identifying genetic determinants of host species in rna viruses.despite environmental, social and ecological dependencies, emergence of zoonotic viruses in human populations is clearly also affected by genetic factors which determine cross-species transmission potential. rna viruses pose an interesting case study given their mutation rates are orders of magnitude higher than any other pathogen--as reflected by the recent emergence of sars and influenza for example. here, we show how feature selection techniques can be used to reliably classify viral sequence ...201324130470
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