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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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
detection of a virus related to betacoronaviruses in italian greater horseshoe bats.the association between coronaviruses and bats is a worldwide phenomenon and bats belonging to genus rhinolophus are the reservoir host for several coronaviruses, including a large number of viruses closely related genetically to severe acute respiratory syndrome-coronavirus (sars-cov). we carried out a survey in colonies of italian bats (rhinolophus ferrumequinum) for the presence of coronaviruses. two of 52 r. ferrumequinum captured from different italian areas tested positive by reverse trans ...201120478089
detection of a virus related to betacoronaviruses in italian greater horseshoe bats.the association between coronaviruses and bats is a worldwide phenomenon and bats belonging to genus rhinolophus are the reservoir host for several coronaviruses, including a large number of viruses closely related genetically to severe acute respiratory syndrome-coronavirus (sars-cov). we carried out a survey in colonies of italian bats (rhinolophus ferrumequinum) for the presence of coronaviruses. two of 52 r. ferrumequinum captured from different italian areas tested positive by reverse trans ...201120478089
orf8a of sars-cov forms an ion channel: experiments and molecular dynamics simulations.orf8a protein is 39 residues long and contains a single transmembrane domain. the protein is synthesized using solid phase peptide synthesis and reconstituted into artificial lipid bilayers that forms cation-selective ion channels with a main conductance level of 8.9±0.8ps at elevated temperature (38.5°c). computational modeling studies including multi nanosecond molecular dynamics simulations in a hydrated popc lipid bilayer are done with a 22 amino acid transmembrane helix to predict a putativ ...201120708597
cd8+ t cell response in hla-a*0201 transgenic mice is elicited by epitopes from sars-cov s protein.cytotoxic cd8(+) t lymphocytes (ctls) play an important role in antiviral immunity. several human hla-a*0201 restricted ctl epitopes of severe acute respiratory syndrome (sars) spike (s) protein have been identified in hla-a*0201 transgenic (tg) mice, but the mechanisms and properties of immune responses are still not well understood. in this study, hla-a*0201 tg mice were primed intramuscularly with sars s dna and boosted subcutaneously with hla-a*0201 restricted peptides. the lymphocytes from ...201020709007
nmr structure of the sars-cov nonstructural protein 7 in solution at ph 6.5.the nmr structure of the severe acute respiratory syndrome coronavirus nonstructural protein (nsp) 7 in aqueous solution at ph 6.5 was determined and compared with the results of previous structure determinations of nsp7 in solution at ph 7.5 and in the crystals of a hexadecameric nsp7/nsp8 complex obtained from a solution at ph 7.5. all three structures contain four helices as the only regular secondary structures, but there are differences in the lengths and sequence locations of the four heli ...201020709084
identification of phenanthroindolizines and phenanthroquinolizidines as novel potent anti-coronaviral agents for porcine enteropathogenic coronavirus transmissible gastroenteritis virus and human severe acute respiratory syndrome coronavirus.the discovery and development of new, highly potent anti-coronavirus agents and effective approaches for controlling the potential emergence of epidemic coronaviruses still remains an important mission. here, we identified tylophorine compounds, including naturally occurring and synthetic phenanthroindolizidines and phenanthroquinolizidines, as potent in vitro inhibitors of enteropathogenic coronavirus transmissible gastroenteritis virus (tgev). the potent compounds showed 50% maximal effective ...201020727913
the american society for virology--29th annual meeting.the american society for virology 29th annual meeting, held in bozeman, mt, usa, included topics covering new vaccine technologies, delivery methods and treatments in the field of virology. this conference report highlights selected presentations on human norovirus (hunov), sars coronavirus and rift valley fever virus vaccine technologies; programmed cell death-1 (pd1) blockade and hyperacute alpha-gal platform technology methods; aerosol vaccination delivery; novel technologies to produce influ ...201020799142
sars-coronavirus protein 6 conformations required to impede protein import into the nucleus.the severe acute respiratory syndrome coronavirus (sars-cov) genome encodes eight accessory proteins. accessory protein 6 is a 63-residue amphipathic peptide that accelerates coronavirus infection kinetics in cell culture and in mice. protein 6 is minimally bifunctional, with an n-terminal lipophilic part implicated in accelerating viral growth and a c-terminal hydrophilic part interfering with general protein import into the nucleus. this interference with nuclear import requires interaction be ...201020800627
update on sars research and other possibly zoonotic coronaviruses.the global outbreak of severe acute respiratory syndrome (sars) in 2003 led to an intense and effective global response that stopped the spread of the disease by july 2003. there was also an intensive and very productive research effort to identify the aetiological agent, characterise the clinical and epidemiological features of the disease, understand the pathogenesis of the disease and the molecular biology of the virus, and design antiviral drugs and vaccines to treat and prevent the disease. ...201020801001
generating stable chinese hamster ovary cell clones to produce a truncated sars-cov spike protein for vaccine development.the spike (s) protein of the severe acute respiratory syndrome coronavirus (sars-cov) is important for vaccine development. s(tr2) (an 88 kda truncated sars-cov tw1 s protein carrying the s fragments s-74-253, s-294-739, and s-1129-1255) is capable of expressing a major form of glycoprotein as endo h-sensitive (∼115 kda) in cho cells. to establish stable expressing cell clones, we transfected cho/dhfr-cells with the amplifiable vectors isid (ires-driven dhfr) and isiz (sv40-driven dhfr) to selec ...201020809484
generating stable chinese hamster ovary cell clones to produce a truncated sars-cov spike protein for vaccine development.the spike (s) protein of the severe acute respiratory syndrome coronavirus (sars-cov) is important for vaccine development. s(tr2) (an 88 kda truncated sars-cov tw1 s protein carrying the s fragments s-74-253, s-294-739, and s-1129-1255) is capable of expressing a major form of glycoprotein as endo h-sensitive (∼115 kda) in cho cells. to establish stable expressing cell clones, we transfected cho/dhfr-cells with the amplifiable vectors isid (ires-driven dhfr) and isiz (sv40-driven dhfr) to selec ...201020809484
vigor, an annotation program for small viral genomes.the decrease in cost for sequencing and improvement in technologies has made it easier and more common for the re-sequencing of large genomes as well as parallel sequencing of small genomes. it is possible to completely sequence a small genome within days and this increases the number of publicly available genomes. among the types of genomes being rapidly sequenced are those of microbial and viral genomes responsible for infectious diseases. however, accurate gene prediction is a challenge that ...201020822531
use of a multiplex pcr/rt-pcr approach to assess the viral causes of influenza-like illnesses in cambodia during three consecutive dry seasons.acute respiratory infections are a major cause of mortality and morbidity worldwide. using multiplex pcr/rt-pcr methods for the detection of 18 respiratory viruses, the circulation of those viruses during 3 consecutive dry seasons in cambodia was described. among 234 patients who presented with influenza-like illness, 35.5% were positive for at least one virus. rhinoviruses (43.4%), parainfluenza (31.3%) viruses and coronaviruses (21.7%) were the most frequently detected viruses. influenza a vir ...201020827775
the membrane protein of severe acute respiratory syndrome coronavirus acts as a dominant immunogen revealed by a clustering region of novel functionally and structurally defined cytotoxic t-lymphocyte epitopes.severe acute respiratory syndrome coronavirus (sars-cov), which emerged with highly contagious and life-threatening characteristics in 2002, remains a potential risk for future outbreaks. membrane (m) and envelope (e) proteins are major structural proteins of the sars-cov. the m protein has been determined as a protective antigen in humoral responses. however, its potential roles in stimulating cellular immunity remain elusive.201020831383
[consecutive five-year follow-up analysis of specific igg antibody of 22 cases of sars patients after recovery].to study igg antibody persistence and temporal change in sars coronavirus (sars-cov) infected patients, 22 patients recovered from sars in beijing were recruited and followed-up from 2004 to 2008, serum samples from patients were collected every year. we checked and analyzed the sars-cov igg antibody (ab) for five consecutive years using the commercial elisa test kit. the results showed that: all of the serum were sars-igg antibody-positive the first year after recovery, the titer of most serum ...201020836383
[the research and application of inhibitory effect of rna-based strategies on sars]. 201020836389
novel immunodominant peptide presentation strategy: a featured hla-a*2402-restricted cytotoxic t-lymphocyte epitope stabilized by intrachain hydrogen bonds from severe acute respiratory syndrome coronavirus nucleocapsid protein.antigenic peptides recognized by virus-specific cytotoxic t lymphocytes (ctls) are presented by major histocompatibility complex (mhc; or human leukocyte antigen [hla] in humans) molecules, and the peptide selection and presentation strategy of the host has been studied to guide our understanding of cellular immunity and vaccine development. here, a severe acute respiratory syndrome coronavirus (sars-cov) nucleocapsid (n) protein-derived ctl epitope, n1 (qfkdnvill), restricted by hla-a*2402 was ...201020844028
the sars coronavirus e protein interacts with pals1 and alters tight junction formation and epithelial morphogenesis.intercellular tight junctions define epithelial apicobasal polarity and form a physical fence which protects underlying tissues from pathogen invasions. pals1, a tight junction-associated protein, is a member of the crumbs3-pals1-patj polarity complex, which is crucial for the establishment and maintenance of epithelial polarity in mammals. here we report that the carboxy-terminal domain of the sars-cov e small envelope protein (e) binds to human pals1. using coimmunoprecipitation and pull-down ...201020861307
the role of sars-cov protein, orf-6, in the induction of host cell death. 201020864743
immunogenetics in sars: a case-control study. 201020864745
simultaneous detection of sars coronavirus and influenza a viruses using real-time polymerase chain reaction. 201020864746
association of a single nucleotide polymorphism in the cd209 (dc-sign) promoter with sars severity. 201020864747
progress towards a sars vaccine. 201020883159
immunogenicity and protective efficacy in mice and hamsters of a β-propiolactone inactivated whole virus sars-cov vaccine.the immunogenicity and efficacy of β-propiolactone (bpl) inactivated whole virion sars-cov (wi-sars) vaccine was evaluated in balb/c mice and golden syrian hamsters. the vaccine preparation was tested with or without adjuvants. adjuvant systems as01(b) and as03(a) were selected and tested for their capacity to elicit high humoral and cellular immune responses to wi-sars vaccine. we evaluated the effect of vaccine dose and each adjuvant on immunogenicity and efficacy in mice, and the effect of va ...201020883165
cd209 (dc-sign) -336a>g promoter polymorphism and severe acute respiratory syndrome in hong kong chinese.cd209 (dc-sign) is an important c-type lectin which acts a receptor of many pathogens. the single nucleotide polymorphism (snp) -336a>g in the cd209 promoter has been demonstrated to regulate promoter activity and to be associated with several important infectious diseases, such as human immunodeficiency virus-1 (hiv-1), mycobacterium tuberculosis, and dengue fever. cd209 facilitates severe acute respiratory syndrome (sars)-coronavirus spike protein-bearing pseudotype driven infection of permiss ...201020359516
mutation of glu-166 blocks the substrate-induced dimerization of sars coronavirus main protease.the maturation of sars coronavirus involves the autocleavage of polyproteins 1a and 1ab by the main protease (mpro) and a papain-like protease; these represent attractive targets for the development of anti-sars drugs. the functional unit of mpro is a homodimer, and each subunit has a his-41cdots, three dots, centeredcys-145 catalytic dyad. current thinking in this area is that mpro dimerization is essential for catalysis, although the influence of the substrate binding on the dimer formation ha ...201020371333
a 219-mer cho-expressing receptor-binding domain of sars-cov s protein induces potent immune responses and protective immunity.development of vaccines is essential for the prevention of future recurrences of severe acute respiratory syndrome (sars), caused by the sars coronavirus (sars-cov). the spike (s) protein, especially receptor-binding domain (rbd) of sars-cov, plays important roles in the prevention of sars infection, and is thus an important component in sars vaccine development. in this study, we expressed a 219-mer (residues 318-536) rbd protein in chinese hamster ovary (cho)-k1 cells (rbd219-cho), and tested ...201020374001
a 219-mer cho-expressing receptor-binding domain of sars-cov s protein induces potent immune responses and protective immunity.development of vaccines is essential for the prevention of future recurrences of severe acute respiratory syndrome (sars), caused by the sars coronavirus (sars-cov). the spike (s) protein, especially receptor-binding domain (rbd) of sars-cov, plays important roles in the prevention of sars infection, and is thus an important component in sars vaccine development. in this study, we expressed a 219-mer (residues 318-536) rbd protein in chinese hamster ovary (cho)-k1 cells (rbd219-cho), and tested ...201020374001
sars-cov pathogenesis is regulated by a stat1 dependent but a type i, ii and iii interferon receptor independent mechanism.severe acute respiratory syndrome coronavirus (sars-cov) infection often caused severe end stage lung disease and organizing phase diffuse alveolar damage, especially in the elderly. the virus-host interactions that governed development of these acute end stage lung diseases and death are unknown. to address this question, we evaluated the role of innate immune signaling in protection from human (urbani) and a recombinant mouse adapted sars-cov, designated rma15. in contrast to most models of vi ...201020386712
quantitative proteomics analysis reveals bag3 as a potential target to suppress severe acute respiratory syndrome coronavirus replication.the discovery of a novel coronavirus (cov) as the causative agent of severe acute respiratory syndrome (sars) has highlighted the need for a better understanding of cov replication. the replication of sars-cov is highly dependent on host cell factors. however, relatively little is known about the cellular proteome changes that occur during sars-cov replication. recently, we developed a cell line expressing a sars-cov subgenomic replicon and used it to screen inhibitors of sars-cov replication. t ...201020392858
mechanistic study of the reaction of thiol-containing enzymes with alpha,beta-unsaturated carbonyl substrates by computation and chemoassays.we investigated the reactions between substituted alpha,beta-unsaturated carbonyl compounds (michael systems) and thiols by computations as well as chemoassays. the results give insight into variations in the underlying mechanisms as a function of the substitution pattern. this is of interest for the mechanisms of inhibition of the sars coronavirus main protease (sars-cov m(pro)) by etacrynic acid derivatives as well as for the excess toxicity of substituted alpha,beta-unsaturated carbonyl compo ...201020401893
effect of mucosal and systemic immunization with virus-like particles of severe acute respiratory syndrome coronavirus in mice.nasal administration has emerged as a promising and attractive route for vaccination, especially for the prophylaxis of respiratory diseases. our previous studies have shown that severe acute respiratory syndrome coronavirus (sars-cov) virus-like particles (vlps) can be assembled using a recombinant baculovirus (rbv) expression system and such vlps induce specific humoral and cellular immune responses in mice after subcutaneous injection. here, we investigated mucosal immune responses to sars-co ...201020406307
the envelope protein of severe acute respiratory syndrome coronavirus interacts with the non-structural protein 3 and is ubiquitinated.to analyze the proteins interacting with the severe acute respiratory syndrome coronavirus (sars-cov) envelope (e) protein, a sars-cov was engineered including two tags associated to the e protein. using this virus, complexes of sars-cov e and other proteins were purified using a tandem affinity purification system. several viral and cell proteins including spike, membrane, non-structural protein 3 (nsp3), dynein heavy chain, fatty acid synthase and transmembrane protein 43 bound e protein. in t ...201020409569
mutation of asn28 disrupts the dimerization and enzymatic activity of sars 3cl(pro) .coronaviruses are responsible for a significant proportion of annual respiratory and enteric infections in humans and other mammals. the most prominent of these viruses is the severe acute respiratory syndrome coronavirus (sars-cov) which causes acute respiratory and gastrointestinal infection in humans. the coronavirus main protease, 3cl(pro), is a key target for broad-spectrum antiviral development because of its critical role in viral maturation and high degree of structural conservation amon ...201020420403
in vitro reconstitution of sars-coronavirus mrna cap methylation.sars-coronavirus (sars-cov) genome expression depends on the synthesis of a set of mrnas, which presumably are capped at their 5' end and direct the synthesis of all viral proteins in the infected cell. sixteen viral non-structural proteins (nsp1 to nsp16) constitute an unusually large replicase complex, which includes two methyltransferases putatively involved in viral mrna cap formation. the s-adenosyl-l-methionine (adomet)-dependent (guanine-n7)-methyltransferase (n7-mtase) activity was recen ...201020421945
production of specific antibodies against sars-coronavirus nucleocapsid protein without cross reactivity with human coronaviruses 229e and oc43.severe acute respiratory syndrome (sars) is a life-threatening disease for which accurate diagnosis is essential. although many tools have been developed for the diagnosis of sars, false-positive reactions in negative sera may occur because of cross-reactivity with other coronaviruses. we have raised polyclonal and monoclonal antibodies (abs) using a recombinant form of the sars virus nucleocapsid protein. cross-reactivity of these anti-sars abs against human coronavirus (hcov) 229e and hcov oc4 ...201020458159
significance of the myxovirus resistance a (mxa) gene -123c>a single-nucleotide polymorphism in suppressed interferon beta induction of severe acute respiratory syndrome coronavirus infection.myxovirus resistance a (mxa) is an antiviral protein induced by interferon alpha and beta (ifn-alpha, ifn-beta) that can inhibit viral replication. the minor alleles of the -88g>t and -123c>a mxa promoter single-nucleotide polymorphisms (snps) are associated with increased promoter activity and altered response to ifn-alpha and ifn-beta treatment. here, we demonstrate that the -123a minor allele provided stronger binding affinity to nuclear proteins extracted from ifn-beta-untreated cells than d ...201020462354
infidelity of sars-cov nsp14-exonuclease mutant virus replication is revealed by complete genome sequencing.most rna viruses lack the mechanisms to recognize and correct mutations that arise during genome replication, resulting in quasispecies diversity that is required for pathogenesis and adaptation. however, it is not known how viruses encoding large viral rna genomes such as the coronaviridae (26 to 32 kb) balance the requirements for genome stability and quasispecies diversity. further, the limits of replication infidelity during replication of large rna genomes and how decreased fidelity impacts ...201020463816
a small-molecule oxocarbazate inhibitor of human cathepsin l blocks severe acute respiratory syndrome and ebola pseudotype virus infection into human embryonic kidney 293t cells.a tetrahydroquinoline oxocarbazate (pubchem cid 23631927) was tested as an inhibitor of human cathepsin l (ec 3.4.22.15) and as an entry blocker of severe acute respiratory syndrome (sars) coronavirus and ebola pseudotype virus. in the cathepsin l inhibition assay, the oxocarbazate caused a time-dependent 17-fold drop in ic(50) from 6.9 nm (no preincubation) to 0.4 nm (4-h preincubation). slowly reversible inhibition was demonstrated in a dilution assay. a transient kinetic analysis using a sing ...201020466822
interactions of sars coronavirus nucleocapsid protein with the host cell proteasome subunit p42.severe acute respiratory syndrome-associated coronavirus (sars-cov) spreads rapidly and has a high case-mortality rate. the nucleocapsid protein (np) of sars-cov may be critical for pathogenicity. this study sought to discover the host proteins that interact with sars-cov np.201020478047
antiproliferative effect of toona sinensis leaf extract on non-small-cell lung cancer.toona sinensis (ts), which is also known as cedrela sinensis, belongs to meliaceae family, the compounds identified from this ts leaves possess a wide range of biologic functions, such as hypoglycemic effects, anti-ldl glycative activity, antioxidant activities, and inhibition of sudden acute respiratory syndrome (sars) coronavirus replication. however, their effect against cancer cells is not well explored. in this study, to understand the cytotoxic effect and molecular mechanism stimulated by ...201020478545
upregulation of the chemokine (c-c motif) ligand 2 via a severe acute respiratory syndrome coronavirus spike-ace2 signaling pathway.severe acute respiratory syndrome coronavirus (sars-cov) was identified to be the causative agent of sars with atypical pneumonia. angiotensin-converting enzyme 2 (ace2) is the major receptor for sars-cov. it is not clear whether ace2 conveys signals from the cell surface to the nucleus and regulates expression of cellular genes upon sars-cov infection. to understand the pathogenesis of sars-cov, human type ii pneumocyte (a549) cells were incubated with the viral spike protein or with sars-cov v ...201020484496
the ubiquitin-proteasome system plays an important role during various stages of the coronavirus infection cycle.the ubiquitin-proteasome system (ups) is a key player in regulating the intracellular sorting and degradation of proteins. in this study we investigated the role of the ups in different steps of the coronavirus (cov) infection cycle. inhibition of the proteasome by different chemical compounds (i.e., mg132, epoxomicin, and velcade) appeared to not only impair entry but also rna synthesis and subsequent protein expression of different covs (i.e., mouse hepatitis virus [mhv], feline infectious per ...201020484504
maturation mechanism of severe acute respiratory syndrome (sars) coronavirus 3c-like proteinase.the 3c-like proteinase (3cl(pro)) of the severe acute respiratory syndrome (sars) coronavirus plays a vital role in virus maturation and is proposed to be a key target for drug design against sars. various in vitro studies revealed that only the dimer of the matured 3cl(pro) is active. however, as the internally encoded 3cl(pro) gets matured from the replicase polyprotein by autolytic cleavage at both the n-terminal and the c-terminal flanking sites, it is unclear whether the polyprotein also ne ...201020489209
sars coronavirus unique domain: three-domain molecular architecture in solution and rna binding.nonstructural protein 3 of the severe acute respiratory syndrome (sars) coronavirus includes a "sars-unique domain" (sud) consisting of three globular domains separated by short linker peptide segments. this work reports nmr structure determinations of the c-terminal domain (sud-c) and a two-domain construct (sud-mc) containing the middle domain (sud-m) and the c-terminal domain, and nmr data on the conformational states of the n-terminal domain (sud-n) and the sud-nm two-domain construct. both ...201020493876
synthesis, docking studies, and evaluation of pyrimidines as inhibitors of sars-cov 3cl protease.a series of 2-(benzylthio)-6-oxo-4-phenyl-1,6-dihydropyrimidine as sars-cov 3cl protease inhibitors were developed and their potency was evaluated by in vitro protease inhibitory assays. two candidates had encouraging results for the development of new anti-sars compounds.201020494577
development of a dose-response model for sars coronavirus.in order to develop a dose-response model for sars coronavirus (sars-cov), the pooled data sets for infection of transgenic mice susceptible to sars-cov and infection of mice with murine hepatitis virus strain 1, which may be a clinically relevant model of sars, were fit to beta-poisson and exponential models with the maximum likelihood method. the exponential model (k= 4.1 x l0(2)) could describe the dose-response relationship of the pooled data sets. the beta-poisson model did not provide a st ...201020497390
elastase-mediated activation of the severe acute respiratory syndrome coronavirus spike protein at discrete sites within the s2 domain.proteolytic priming is a common method of controlling the activation of membrane fusion mediated by viral glycoproteins. the severe acute respiratory syndrome coronavirus spike protein (sars-cov s) can be primed by a variety of host cell proteases, with proteolytic cleavage occurring both as the s1/s2 boundary and adjacent to a fusion peptide in the s2 domain. here, we studied the priming of sars-cov s by elastase and show an important role for residue thr(795) in the s2 domain. a series of alan ...201020507992
severe acute respiratory syndrome coronavirus papain-like novel protease inhibitors: design, synthesis, protein-ligand x-ray structure and biological evaluation.the design, synthesis, x-ray crystal structure, molecular modeling, and biological evaluation of a series of new generation sars-cov plpro inhibitors are described. a new lead compound 3 (6577871) was identified via high-throughput screening of a diverse chemical library. subsequently, we carried out lead optimization and structure-activity studies to provide a series of improved inhibitors that show potent plpro inhibition and antiviral activity against sars-cov infected vero e6 cells. interest ...201020527968
t cell epitope specificity and pathogenesis of mouse hepatitis virus-1-induced disease in susceptible and resistant hosts.intranasal mouse hepatitis virus-1 (mhv-1) infection of susceptible mouse strains mimics some important pathologic features observed in the lungs of severe acute respiratory syndrome (sars)-coronavirus-infected humans. the pathogenesis of sars remains poorly understood, although increasing evidence suggests that immunopathology could play an important role. we previously reported that the adaptive immune response plays an important protective role in mhv-1-infected resistant b6 mice and that bot ...201020554960
angiotensin-converting enzyme 2 (ace2) proteins of different bat species confer variable susceptibility to sars-cov entry.the discovery of sars-like coronavirus in bats suggests that bats could be the natural reservoir of sars-cov. however, previous studies indicated the angiotensin-converting enzyme 2 (ace2) protein, a known sars-cov receptor, from a horseshoe bat was unable to act as a functional receptor for sars-cov. here, we extended our previous study to ace2 molecules from seven additional bat species and tested their interactions with human sars-cov spike protein using both hiv-based pseudotype and live sar ...201020567988
angiotensin-converting enzyme 2 (ace2) proteins of different bat species confer variable susceptibility to sars-cov entry.the discovery of sars-like coronavirus in bats suggests that bats could be the natural reservoir of sars-cov. however, previous studies indicated the angiotensin-converting enzyme 2 (ace2) protein, a known sars-cov receptor, from a horseshoe bat was unable to act as a functional receptor for sars-cov. here, we extended our previous study to ace2 molecules from seven additional bat species and tested their interactions with human sars-cov spike protein using both hiv-based pseudotype and live sar ...201020567988
the cellular rna helicase ddx1 interacts with coronavirus nonstructural protein 14 and enhances viral replication.the involvement of host proteins in the replication and transcription of viral rna is a poorly understood area for many rna viruses. for coronaviruses, it was long speculated that replication of the giant rna genome and transcription of multiple subgenomic mrna species by a unique discontinuous transcription mechanism may require host cofactors. to search for such cellular proteins, yeast two-hybrid screening was carried out by using the nonstructural protein 14 (nsp14) from the coronavirus infe ...201020573827
a single asparagine-linked glycosylation site of the severe acute respiratory syndrome coronavirus spike glycoprotein facilitates inhibition by mannose-binding lectin through multiple mechanisms.mannose-binding lectin (mbl) is a serum protein that plays an important role in host defenses as an opsonin and through activation of the complement system. the objective of this study was to assess the interactions between mbl and severe acute respiratory syndrome-coronavirus (sars-cov) spike (s) glycoprotein (sars-s). mbl was found to selectively bind to retroviral particles pseudotyped with sars-s. unlike several other viral envelopes to which mbl can bind, both recombinant and plasma-derived ...201020573835
a cost-based comparison of quarantine strategies for new emerging diseases.a classical epidemiological framework is used to provide a preliminary cost analysis of the effects of quarantine and isolation on the dynamics of infectious diseases for which no treatment or immediate diagnosis tools are available. within this framework we consider the cost incurred from the implementation of three types of dynamic control strategies. taking the context of the 2003 sars outbreak in hong kong as an example, we use a simple cost function to compare the total cost of each mixed ( ...201020578793
palmitoylation of sars-cov s protein is necessary for partitioning into detergent-resistant membranes and cell-cell fusion but not interaction with m protein.coronaviruses are enveloped rna viruses that generally cause mild disease in humans. however, the recently emerged coronavirus that caused severe acute respiratory syndrome (sars-cov) is the most pathogenic human coronavirus discovered to date. the sars-cov spike (s) protein mediates virus entry by binding cellular receptors and inducing fusion between the viral envelope and the host cell membrane. coronavirus s proteins are palmitoylated, which may affect function. here, we created a non-palmit ...201020580052
essential covalent linkage between the chymotrypsin-like domain and the extra domain of the sars-cov main protease.the main protease of the coronavirus causing severe acute respiratory syndrome performs proteolytic processing of the viral polyproteins. the active form of the enzyme is a homodimer with each subunit consisting of three structural domains. domains i and ii, hosting the complete catalytic machinery, constitute the n-terminal chymotrypsin-like folding scaffold and connect to the extra c-terminal domain iii by a long loop. previously, the domain iii-truncated enzyme was demonstrated to fold indepe ...201020587646
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