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synthesis and anti-coronavirus activity of a series of 1-thia-4-azaspiro[4.5]decan-3-one derivatives.a series of 1-thia-4-azaspiro[4.5]decan-3-ones bearing an amide group at c-4 and various substitutions at c-2 and c-8 were synthesized and evaluated against human coronavirus and influenza virus. compounds 7m, 7n, 8k, 8l, 8m, 8n, and 8p were found to inhibit human coronavirus 229e replication. the most active compound was n-(2-methyl-8-tert-butyl-3-oxo-1-thia-4-azaspiro[4.5]decan-4-yl)-3-phenylpropanamide (8n), with an ec50 value of 5.5 µm, comparable to the known coronavirus inhibitor, (z)-n-[3 ...201931073993
identification and characterization of a human coronavirus 229e nonstructural protein 8-associated rna 3'-terminal adenylyltransferase activity.coronavirus nonstructural protein 8 (nsp8) has been suggested to have diverse activities, including noncanonical template-dependent polymerase activities. here, we characterized a recombinant form of the human coronavirus 229e (hcov-229e) nsp8 and found that the protein has metal ion-dependent rna 3'-terminal adenylyltransferase (tatase) activity, while other nucleotides were not (or very inefficiently) transferred to the 3' ends of single-stranded and (fully) double-stranded acceptor rnas. usin ...201930918070
respiratory pathogens in infants diagnosed with acute lower respiratory tract infection in a tertiary care hospital of western india using multiplex real time pcr.to determine the frequency of respiratory pathogens in infants diagnosed with acute lower respiratory tract infections.201930637585
viral acute respiratory illnesses in young infants increase the risk of respiratory readmission.respiratory viruses cause acute respiratory illness (ari) in early childhood, but their effect on subsequent ari admissions is not fully understood. this study aimed to determine the association between initial ari admission because of viruses including human rhinovirus (hrv), respiratory syncytial virus (rsv), human adenovirus (hadv) and human metapneumovirus (hmpv) and the risk of ari readmission in children.201830408004
synthesis, biological evaluation and molecular modeling of a novel series of fused 1,2,3-triazoles as potential anti-coronavirus agents.synthesis and biological evaluation of a novel library of fused 1,2,3-triazole derivatives are described. the in-house developed multicomponent reaction based on commercially available starting materials was applied and broad biological screening against various viruses was performed, showing promising antiviral properties for compounds 14d, 14n, 14q, 18f and 18i against human coronavirus 229e. further in silico studies identified the key molecular interactions between those compounds and the 3- ...201830286952
viral etiological causes of febrile seizures for respiratory pathogens (efes study).febrile seizure is the most common childhood neurological disorder, is an important health problem with potential short- and long-term complications, also leading to economic burden and increased parental anxiety about fevers and seizures occurring in their children. there are no routine recommendation to detect etiological causes of fs for neurological perspective, further knowledge about the etiological causes of fs in children will support preventive measures and follow-up strategies. the aim ...201930235060
antiviral innate immune response in non-myeloid cells is augmented by chloride ions via an increase in intracellular hypochlorous acid levels.phagocytes destroy ingested microbes by producing hypochlorous acid (hocl) from chloride ions (cl-) and hydrogen peroxide within phagolysosomes, using the enzyme myeloperoxidase. hocl, the active ingredient in bleach, has antibacterial/antiviral properties. as myeloperoxidase is needed for hocl production, non-myeloid cells are considered incapable of producing hocl. here, we show that epithelial, fibroblast and hepatic cells have enhanced antiviral activity in the presence of increasing concent ...201830206371
crystal structure of the post-fusion core of the human coronavirus 229e spike protein at 1.86 å resolution.human coronavirus 229e (hcov-229e) usually causes mild upper respiratory infections in heathy adults, but may lead to severe complications or mortality in individuals with weakened immune systems. virus entry of hcov-229e is mediated by its spike (s) protein, where the s1 domain facilitates attachment to host cells and the s2 domain is involved in subsequent fusion of the virus and host membranes. during the fusion process, two heptad repeats, hr1 and hr2, in the s2 domain assemble into a six-he ...201830198895
a rare case of human coronavirus 229e associated with acute respiratory distress syndrome in a healthy adult.human coronavirus 229e (hcov-229e) is one of the first coronavirus strains being described. it is linked to common cold symptoms in healthy adults. younger children and the elderly are considered vulnerable to developing lower respiratory tract infections (lrtis). in particular, immunocompromised patients have been reported with severe and life-threatening lrtis attributed to hcov-229e. we report for the first time a case of lrti and acute respiratory distress syndrome developed in a healthy adu ...201829850307
evaluation of the antimicrobial efficacy and skin safety of a novel color additive in combination with chlorine disinfectants.a novel color additive colorizes chlorine disinfectants blue to improve visibility and enhance spray surface coverage, and it fades to colorless to indicate elapsed contact time. we investigated its interactions with 3 chlorine disinfectants to determine if the additive would adversely affect the disinfectants' antimicrobial efficacy or skin safety.201829803593
hcov-229e spike protein fusion activation by trypsin-like serine proteases is mediated by proteolytic processing in the s2' region.human coronavirus 229e (hcov-229e) is responsible for common colds. like other coronaviruses, hcov-229e exploits cellular proteases to activate fusion mediated by the spike protein. we analysed the proteolytic processing of the hcov-229e spike protein by trypsin-like serine proteases leading to activation of the fusion process. unlike in other coronaviruses, hcov-229e fusion activation appears to be a one-step process. indeed, cleavage of the s1/s2 interface does not seem to be a prerequisite, a ...201829786498
structural characterization of the hcov-229e fusion core.hcov-229e spike (s) protein mediates virion attachment to cells and subsequent fusion of the viral and cellular membranes. this protein is composed of an n-terminal receptor-binding domain (s1) and a c-terminal trans-membrane fusion domain (s2). s2 contains a highly conserved heptad repeat 1 and 2 (hr1 and hr2). in this study, the hrs sequences were designed and connected with a flexible linker. the recombinant fusion core protein was crystallized and its structure was solved at a resolution of ...201829458023
peptide-based membrane fusion inhibitors targeting hcov-229e spike protein hr1 and hr2 domains.human coronavirus 229e (hcov-229e) infection in infants, elderly people, and immunocompromised patients can cause severe disease, thus calling for the development of effective and safe therapeutics to treat it. here we reported the design, synthesis and characterization of two peptide-based membrane fusion inhibitors targeting hcov-229e spike protein heptad repeat 1 (hr1) and heptad repeat 2 (hr2) domains, 229e-hr1p and 229e-hr2p, respectively. we found that 229e-hr1p and 229e-hr2p could interac ...201829415501
renin-angiotensin system in human coronavirus pathogenesis.although initially considered relatively harmless pathogens, human coronaviruses (hcovs) are nowadays known to be associated with more severe clinical complications. still, their precise pathogenic potential is largely unknown, particularly regarding the most recently identified species hcov-nl63 and hcov-hku1. hcovs need host cell proteins to successively establish infections. proteases of the renin-angiotensin system serve as receptors needed for entry into target cells; this article describes ...201032201502
peptide microarrays with site-specifically immobilized synthetic peptides for antibody diagnostics.peptide microarrays bear the potential to discover molecular recognition events on protein level, particularly in the field of molecular immunology, in a manner and with an efficiency comparable to the performance of dna microarrays. we developed a novel peptide microarray platform for the detection of antibodies in liquid samples. the system comprises site-specific solution phase coupling of biotinylated peptides to neutravidin, localized microdispensing of peptide-neutravidin conjugates onto a ...200632288236
spike protein homology between the sars-associated virus and murine hepatitis virus implies existence of a putative receptor-binding region.coronavirus has been determined to be the cause of the recent outbreak of severe acute respiratory syndrome (sars). human coronavirus 229e had been studied well and its receptor-binding domain was restricted to aa417-547 of s protein. however, this region has no homology with the newly separated sars-associated virus (hong kong isolate cuhk-w1). then we analyzed the phylogenesis of s1 subunit of the coronavirus spike protein (sars-associated virus, hong kong isolate cuhk-w1). interestingly, the ...200332214699
the gut viral metagenome analysis of domestic dogs captures snapshot of viral diversity and potential risk of coronavirus.the close relations between dogs (canis lupus familiaris) and humans lay a foundation for cross species transmissions of viruses. the co-existence of multiplex viruses in the host accelerate viral variations. for effective prediction and prevention of potential epidemic or even pandemic, the metagenomics method was used to investigate the gut virome status of 45 domestic healthy dogs which have extensive contact with human beings. a total of 248.6 gb data (505, 203, 006 valid reads, 150 bp in le ...202134307533
coronavirus-specific antibody cross reactivity in rhesus macaques following sars-cov-2 vaccination and infection.vaccines are being rapidly developed with the goal of ending the sars-cov-2 pandemic. however, the extent to which sars-cov-2 vaccination induces serum responses that cross-react with other coronaviruses remains poorly studied. here we define serum profiles in rhesus macaques after vaccination with dna or ad26 based vaccines expressing sars-cov-2 spike protein followed by sars-cov-2 challenge, or sars-cov-2 infection alone. analysis of serum responses showed robust reactivity to the sars-cov-2 f ...202133692201
caco-2 cells: a continuous cell line with sensitive and broad-spectrum utility for respiratory virus culture.primary rhesus monkey kidney cells (rhmk) can be used for the detection of respiratory viruses, including influenza and parainfluenza. the human colon adeno-carcinoma cell line, caco-2, has been previously used for the growth of multiple influenza viruses, including seasonal, novel and avian lineages.202133676967
molecular evolution of human coronavirus 229e in hong kong and a fatal covid-19 case involving coinfection with a novel human coronavirus 229e genogroup.compared to other human coronaviruses, the genetic diversity and evolution of human coronavirus 229e (hcov-229e) are relatively understudied. we report a fatal case of covid-19 pneumonia coinfected with hcov-229e in hong kong. genome sequencing of sars-cov-2 and hcov-229e from a nasopharyngeal sample of the patient showed that the sars-cov-2 strain hk13 was most closely related to sars-cov-2 type strain wuhan-hu-1 (99.99% nucleotide identity), compatible with his recent history of travel to wuha ...202133568452
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