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                  <text>Coronavirus</text>
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                  <text>Dominio científico: Coronavirus</text>
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                <text>Prevalence and genetic diversity analysis of human coronavirus OC43 among adult patients with acute respiratory infections in Beijing, 2012.</text>
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                <text>Qin Hu, Rou-Jian Lu, Kun Peng, Xijie Duan, Yan-Qun Wang, Yanjie Zhao, Wen Wang, Yongliang Lou, Wen-Jie Tan</text>
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                <text>To determine the prevalence, epidemiology and genetic diversity of human coronavirus OC43 (HCoV-OC43) among adult patients with acute respiratory infections (ARI) in Beijing,five hundred and fifty-nine nasopharyngeal swab samples were collected from adult patients with ARI in Beijing. The prevalence of HCoV-OC43 infection among these patients was assessed using two different OneStep reverse transcription polymerase chain reaction (RT-PCR) assays. The epidemiological profiles of the patients with HCoV-OC43 infection were described. Partial S and N genes of HCoV-OC43 circulating strains were sequenced followed by phylogenetic analysis and amino acid alignment. Our results showed that the prevalence of HCoV-OC43 infection was 12.52% (95% CI: 9.78-15.26%), and the epidemic peak occurred in autumn. Fifty partial S and 40 partial N fragments were obtained from these patients. Phylogenetic analysis based on neighbour-joining method showed that at least three distinct clusters (A, B, C/D) of HCoV-OC43 strains were circulating among adult patients with ARI in Beijing. In addition, some novel unique clusters (UNT) of HCoV-OC43 were found in the S- and N-based phylogenetic trees. Furthermore, consensus amino acids substitutes for each cluster were also found after alignment of partial S or N sequence coding region in this study. In conclusion, we herein describe the prevalence of HCoV-OC43 among adult patients and provide substantial evidence for the genetic diversity of HCoV-OC43 circulating in Beijing.</text>
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                <text>DOI: 10.1371/journal.pone.0100781</text>
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                <text>PLoS ONE</text>
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                  <text>Dominio científico: Coronavirus</text>
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                <text>Systematics and molecular phylogeny of the family oscarellidae (homoscleromorpha) with description of two new oscarella species.</text>
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                <text>Eve Gazave, Dennis V Lavrov, Jory Cabrol, Emmanuelle Renard, Caroline Rocher, Jean Vacelet, Maja Adamska, Carole Borchiellini, Alexander V. Ereskovsky</text>
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                <text>The family Oscarellidae is one of the two families in the class Homoscleromorpha (phylum Porifera) and is characterized by the absence of a skeleton and the presence of a specific mitochondrial gene, tatC. This family currently encompasses sponges in two genera: Oscarella with 17 described species and Pseudocorticium with one described species. Although sponges in this group are relatively well-studied, phylogenetic relationships among members of Oscarellidae and the validity of genus Pseudocorticium remain open questions. Here we present a phylogenetic analysis of Oscarellidae using four markers (18S rDNA, 28S rDNA, atp6, tatC), and argue that it should become a mono-generic family, with Pseudocorticium being synonymized with Oscarella, and with the transfer of Pseudocorticium jarrei to Oscarella jarrei. We show that the genus Oscarella can be subdivided into four clades, each of which is supported by either a small number of morphological characters or by molecular synapomorphies. In addition, we describe two new species of Oscarella from Norwegian fjords: O. bergenensis sp. nov. and O. nicolae sp. nov., and we compare their morphology, anatomy, and cytology with other species in this genus. Internal anatomical characters are similar in both species, but details of external morphology and particularly of cytological characters provide diagnostic features. Our study also confirms that O. lobularis and O. tuberculata are two distinct polychromic sibling species. This study highlights the difficulties of species identification in skeleton-less sponges and, more generally, in groups where morphological characters are scarce. Adopting a multi-marker approach is thus highly suitable for these groups.</text>
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                <text>DOI: 10.1371/journal.pone.0063976</text>
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                <text>PLoS ONE</text>
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                <text>Public Library of Science (PLoS)</text>
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                  <text>Dominio científico: Coronavirus</text>
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                <text>Anti-HIV-1 activity of a new scorpion venom peptide derivative Kn2-7.</text>
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                <text>Yaoqing Chen, Luyang Cao, Maohua Zhong, Yan Zhang, Chen Han, Qiaoli Li, Jingyi Yang, Dihan Zhou, Wei Shi, Benxia He, Fang Liu, Jie Yu, Ying Sun, Yuan Cao, Yaoming Li, Wenxin Li, Deying Guo, Zhijian Cao, Huimin Yan</text>
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                <text>For over 30 years, HIV/AIDS has wreaked havoc in the world. In the absence of an effective vaccine for HIV, development of new anti-HIV agents is urgently needed. We previously identified the antiviral activities of the scorpion-venom-peptide-derived mucroporin-M1 for three RNA viruses (measles viruses, SARS-CoV, and H5N1). In this investigation, a panel of scorpion venom peptides and their derivatives were designed and chosen for assessment of their anti-HIV activities. A new scorpion venom peptide derivative Kn2-7 was identified as the most potent anti-HIV-1 peptide by screening assays with an EC(50) value of 2.76 µg/ml (1.65 µM) and showed low cytotoxicity to host cells with a selective index (SI) of 13.93. Kn2-7 could inhibit all members of a standard reference panel of HIV-1 subtype B pseudotyped virus (PV) with CCR5-tropic and CXCR4-tropic NL4-3 PV strain. Furthermore, it also inhibited a CXCR4-tropic replication-competent strain of HIV-1 subtype B virus. Binding assay of Kn2-7 to HIV-1 PV by Octet Red system suggested the anti-HIV-1 activity was correlated with a direct interaction between Kn2-7 and HIV-1 envelope. These results demonstrated that peptide Kn2-7 could inhibit HIV-1 by direct interaction with viral particle and may become a promising candidate compound for further development of microbicide against HIV-1.</text>
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                <text>2012</text>
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                <text>DOI: 10.1371/journal.pone.0034947</text>
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                <text>PLoS ONE</text>
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                <text>Public Library of Science (PLoS)</text>
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                  <text>Coronavirus</text>
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                  <text>Dominio científico: Coronavirus</text>
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                <text>A computational framework to assess genome-wide distribution of polymorphic human endogenous retrovirus-K In human populations.</text>
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                <text>Weiling Li, Lin Lin, Raunaq Malhotra, Lei YANG, Raj Acharya, Mary Poss</text>
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                <text>Human Endogenous Retrovirus type K (HERV-K) is the only HERV known to be insertionally polymorphic; not all individuals have a retrovirus at a specific genomic location. It is possible that HERV-Ks contribute to human disease because people differ in both number and genomic location of these retroviruses. Indeed viral transcripts, proteins, and antibody against HERV-K are detected in cancers, auto-immune, and neurodegenerative diseases. However, attempts to link a polymorphic HERV-K with any disease have been frustrated in part because population prevalence of HERV-K provirus at each polymorphic site is lacking and it is challenging to identify closely related elements such as HERV-K from short read sequence data. We present an integrated and computationally robust approach that uses whole genome short read data to determine the occupation status at all sites reported to contain a HERV-K provirus. Our method estimates the proportion of fixed length genomic sequence (k-mers) from whole genome sequence data matching a reference set of k-mers unique to each HERV-K locus and applies mixture model-based clustering of these values to account for low depth sequence data. Our analysis of 1000 Genomes Project Data (KGP) reveals numerous differences among the five KGP super-populations in the prevalence of individual and co-occurring HERV-K proviruses; we provide a visualization tool to easily depict the proportion of the KGP populations with any combination of polymorphic HERV-K provirus. Further, because HERV-K is insertionally polymorphic, the genome burden of known polymorphic HERV-K is variable in humans; this burden is lowest in East Asian (EAS) individuals. Our study identifies population-specific sequence variation for HERV-K proviruses at several loci. We expect these resources will advance research on HERV-K contributions to human diseases.</text>
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                <text>2019</text>
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                <text>DOI: 10.1371/journal.pcbi.1006564</text>
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                <text>PLoS Computational Biology</text>
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                <text>Biology (General)</text>
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              <name>Description</name>
              <description>An account of the resource</description>
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                  <text>Dominio científico: Coronavirus</text>
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                <text>RNase L mediated protection from virus induced demyelination.</text>
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            <description>An entity primarily responsible for making the resource</description>
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                <text>Derek D. C. Ireland, Stephen A. Stohlman, David R. Hinton, Parul Kapil, Robert H. Silverman, Roscoe A Atkinson, Cornelia C. Bergmann</text>
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                <text>IFN-alpha/beta plays a critical role in limiting viral spread, restricting viral tropism and protecting mice from neurotropic coronavirus infection. However, the IFN-alpha/beta dependent mechanisms underlying innate anti-viral functions within the CNS are poorly understood. The role of RNase L in viral encephalomyelitis was explored based on its functions in inhibiting translation, inducing apoptosis, and propagating the IFN-alpha/beta pathway through RNA degradation intermediates. Infection of RNase L deficient (RL(-/-)) mice with a sub-lethal, demyelinating mouse hepatitis virus variant revealed that the majority of mice succumbed to infection by day 12 p.i. However, RNase L deficiency did not affect overall control of infectious virus, or diminish IFN-alpha/beta expression in the CNS. Furthermore, increased morbidity and mortality could not be attributed to altered proinflammatory signals or composition of cells infiltrating the CNS. The unique phenotype of infected RL(-/-) mice was rather manifested in earlier onset and increased severity of demyelination and axonal damage in brain stem and spinal cord without evidence for enhanced neuronal infection. Increased tissue damage coincided with sustained brain stem infection, foci of microglia infection in grey matter, and increased apoptotic cells. These data demonstrate a novel protective role for RNase L in viral induced CNS encephalomyelitis, which is not reflected in overall viral control or propagation of IFN-alpha/beta mediated signals. Protective function is rather associated with cell type specific and regional restriction of viral replication in grey matter and ameliorated neurodegeneration and demyelination.</text>
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                <text>2009</text>
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                <text>DOI: 10.1371/journal.ppat.1000602</text>
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                <text>PLoS Pathogens</text>
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            <description>An entity responsible for making the resource available</description>
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                <text>Biology (General), Immunologic diseases. Allergy</text>
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            </elementTextContainer>
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            <description>A language of the resource</description>
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                <text>EN</text>
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              <name>Title</name>
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                  <text>Coronavirus</text>
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            <element elementId="41">
              <name>Description</name>
              <description>An account of the resource</description>
              <elementTextContainer>
                <elementText elementTextId="2">
                  <text>Dominio científico: Coronavirus</text>
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              </elementTextContainer>
            </element>
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      <name>Text</name>
      <description>A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.</description>
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                <text>Time course and cellular localization of SARS-CoV nucleoprotein and RNA in lungs from fatal cases of SARS.</text>
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            <description>An entity primarily responsible for making the resource</description>
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              <elementText elementTextId="4269">
                <text>John M. Nicholls, Jagdish Butany, Leo L.M. Poon, Kwok H. Chan, Swan Lip Beh, Susan Poutanen, JS Malik Peiris, Maria Wong</text>
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            <description>An account of the resource</description>
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              <elementText elementTextId="4270">
                <text>Cellular localization of severe acute respiratory syndrome coronavirus (SARS-CoV) in the lungs of patients with SARS is important in confirming the etiological association of the virus with disease as well as in understanding the pathogenesis of the disease. To our knowledge, there have been no comprehensive studies investigating viral infection at the cellular level in humans.We collected the largest series of fatal cases of SARS with autopsy material to date by merging the pathological material from two regions involved in the 2003 worldwide SARS outbreak in Hong Kong, China, and Toronto, Canada. We developed a monoclonal antibody against the SARS-CoV nucleoprotein and used it together with in situ hybridization (ISH) to analyze the autopsy lung tissues of 32 patients with SARS from Hong Kong and Toronto. We compared the results of these assays with the pulmonary pathologies and the clinical course of illness for each patient. SARS-CoV nucleoprotein and RNA were detected by immunohistochemistry and ISH, respectively, primarily in alveolar pneumocytes and, less frequently, in macrophages. Such localization was detected in four of the seven patients who died within two weeks of illness onset, and in none of the 25 patients who died later than two weeks after symptom onset.The pulmonary alveolar epithelium is the chief target of SARS-CoV, with macrophages infected subsequently. Viral replication appears to be limited to the first two weeks after symptom onset, with little evidence of continued widespread replication after this period. If antiviral therapy is considered for future treatment, it should be focused on this two-week period of acute clinical disease.</text>
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                <text>2006</text>
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            <description>An unambiguous reference to the resource within a given context</description>
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              <elementText elementTextId="4272">
                <text>DOI: 10.1371/journal.pmed.0030027</text>
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            <description>A related resource from which the described resource is derived</description>
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              <elementText elementTextId="4273">
                <text>PLoS Medicine</text>
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            <description>An entity responsible for making the resource available</description>
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              <elementText elementTextId="4274">
                <text>Public Library of Science (PLoS)</text>
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            <name>Coverage</name>
            <description>The spatial or temporal topic of the resource, the spatial applicability of the resource, or the jurisdiction under which the resource is relevant</description>
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                <text>Medicine</text>
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            </elementTextContainer>
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            <description>A language of the resource</description>
            <elementTextContainer>
              <elementText elementTextId="4276">
                <text>EN</text>
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  <item itemId="465" public="1" featured="0">
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              <name>Title</name>
              <description>A name given to the resource</description>
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                  <text>Coronavirus</text>
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            <element elementId="41">
              <name>Description</name>
              <description>An account of the resource</description>
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                  <text>Dominio científico: Coronavirus</text>
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      <name>Text</name>
      <description>A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.</description>
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            <description>A name given to the resource</description>
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              <elementText elementTextId="4277">
                <text>Enhanced regulatory sequence prediction using gapped k-mer features.</text>
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            <name>Creator</name>
            <description>An entity primarily responsible for making the resource</description>
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              <elementText elementTextId="4278">
                <text>Mahmoud Ghandi, Dong Won Lee, Morteza Mohammad-Noori, Michael A Beer</text>
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            <name>Description</name>
            <description>An account of the resource</description>
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              <elementText elementTextId="4279">
                <text>Oligomers of length k, or k-mers, are convenient and widely used features for modeling the properties and functions of DNA and protein sequences. However, k-mers suffer from the inherent limitation that if the parameter k is increased to resolve longer features, the probability of observing any specific k-mer becomes very small, and k-mer counts approach a binary variable, with most k-mers absent and a few present once. Thus, any statistical learning approach using k-mers as features becomes susceptible to noisy training set k-mer frequencies once k becomes large. To address this problem, we introduce alternative feature sets using gapped k-mers, a new classifier, gkm-SVM, and a general method for robust estimation of k-mer frequencies. To make the method applicable to large-scale genome wide applications, we develop an efficient tree data structure for computing the kernel matrix. We show that compared to our original kmer-SVM and alternative approaches, our gkm-SVM predicts functional genomic regulatory elements and tissue specific enhancers with significantly improved accuracy, increasing the precision by up to a factor of two. We then show that gkm-SVM consistently outperforms kmer-SVM on human ENCODE ChIP-seq datasets, and further demonstrate the general utility of our method using a Naïve-Bayes classifier. Although developed for regulatory sequence analysis, these methods can be applied to any sequence classification problem.</text>
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                <text>2014</text>
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            <description>An unambiguous reference to the resource within a given context</description>
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              <elementText elementTextId="4281">
                <text>DOI: 10.1371/journal.pcbi.1003711</text>
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            <description>A related resource from which the described resource is derived</description>
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              <elementText elementTextId="4282">
                <text>PLoS Computational Biology</text>
              </elementText>
            </elementTextContainer>
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            <name>Publisher</name>
            <description>An entity responsible for making the resource available</description>
            <elementTextContainer>
              <elementText elementTextId="4283">
                <text>Public Library of Science (PLoS)</text>
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            <description>The spatial or temporal topic of the resource, the spatial applicability of the resource, or the jurisdiction under which the resource is relevant</description>
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                <text>Biology (General)</text>
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            <description>A language of the resource</description>
            <elementTextContainer>
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                <text>EN</text>
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              <name>Title</name>
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                  <text>Coronavirus</text>
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              <name>Description</name>
              <description>An account of the resource</description>
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                  <text>Dominio científico: Coronavirus</text>
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      <name>Text</name>
      <description>A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.</description>
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                <text>Anatomy of the epidemiological literature on the 2003 SARS outbreaks in Hong Kong and Toronto: a time-stratified review.</text>
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              <elementText elementTextId="4287">
                <text>Weijia Xing, Gilles Hejblum, Gabriel M. Leung, Alain-Jacques Valleron</text>
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                <text>BACKGROUND: Outbreaks of emerging infectious diseases, especially those of a global nature, require rapid epidemiological analysis and information dissemination. The final products of those activities usually comprise internal memoranda and briefs within public health authorities and original research published in peer-reviewed journals. Using the 2003 severe acute respiratory syndrome (SARS) epidemic as an example, we conducted a comprehensive time-stratified review of the published literature to describe the different types of epidemiological outputs. METHODS AND FINDINGS: We identified and analyzed all published articles on the epidemiology of the SARS outbreak in Hong Kong or Toronto. The analysis was stratified by study design, research domain, data collection, and analytical technique. We compared the SARS-case and matched-control non-SARS articles published according to the timeline of submission, acceptance, and publication. The impact factors of the publishing journals were examined according to the time of publication of SARS articles, and the numbers of citations received by SARS-case and matched-control articles submitted during and after the epidemic were compared. Descriptive, analytical, theoretical, and experimental epidemiology concerned, respectively, 54%, 30%, 11%, and 6% of the studies. Only 22% of the studies were submitted, 8% accepted, and 7% published during the epidemic. The submission-to-acceptance and acceptance-to-publication intervals of the SARS articles submitted during the epidemic period were significantly shorter than the corresponding intervals of matched-control non-SARS articles published in the same journal issues (p</text>
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                <text>2010</text>
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                <text>DOI: 10.1371/journal.pmed.1000272</text>
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                <text>PLoS Medicine</text>
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                <text>Public Library of Science (PLoS)</text>
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                <text>Medicine</text>
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                  <text>Dominio científico: Coronavirus</text>
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                <text>Biochemical and structural insights into the mechanisms of SARS coronavirus RNA ribose 2'-O-methylation by nsp16/nsp10 protein complex.</text>
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              <elementText elementTextId="4296">
                <text>Yu Chen, Ceyang Su, Min Ke, Xu Jin, Lirong Xu, Zhou Zhang, Andong Wu, Ying Sun, Zhouning Yang, Po Tien, Tero Ahola, Yi Liang, Xinqi Liu, Deyin Guo</text>
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                <text>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. A unique feature for SARS-CoV is that nsp16 requires non-structural protein nsp10 as a stimulatory factor to execute its MTase activity. Here we report the biochemical characterization of SARS-CoV 2'-O-MTase and the crystal structure of nsp16/nsp10 complex bound with methyl donor SAM. We found that SARS-CoV nsp16 MTase methylated m7GpppA-RNA but not m7GpppG-RNA, which is in contrast with nsp14 MTase that functions in a sequence-independent manner. We demonstrated that nsp10 is required for nsp16 to bind both m7GpppA-RNA substrate and SAM cofactor. Structural analysis revealed that nsp16 possesses the canonical scaffold of MTase and associates with nsp10 at 1∶1 ratio. The structure of the nsp16/nsp10 interaction interface shows that nsp10 may stabilize the SAM-binding pocket and extend the substrate RNA-binding groove of nsp16, consistent with the findings in biochemical assays. These results suggest that nsp16/nsp10 interface may represent a better drug target than the viral MTase active site for developing highly specific anti-coronavirus drugs.</text>
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            <name>Date</name>
            <description>A point or period of time associated with an event in the lifecycle of the resource</description>
            <elementTextContainer>
              <elementText elementTextId="4298">
                <text>2011</text>
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            <name>Identifier</name>
            <description>An unambiguous reference to the resource within a given context</description>
            <elementTextContainer>
              <elementText elementTextId="4299">
                <text>DOI: 10.1371/journal.ppat.1002294</text>
              </elementText>
            </elementTextContainer>
          </element>
          <element elementId="48">
            <name>Source</name>
            <description>A related resource from which the described resource is derived</description>
            <elementTextContainer>
              <elementText elementTextId="4300">
                <text>PLoS Pathogens</text>
              </elementText>
            </elementTextContainer>
          </element>
          <element elementId="45">
            <name>Publisher</name>
            <description>An entity responsible for making the resource available</description>
            <elementTextContainer>
              <elementText elementTextId="4301">
                <text>Public Library of Science (PLoS)</text>
              </elementText>
            </elementTextContainer>
          </element>
          <element elementId="38">
            <name>Coverage</name>
            <description>The spatial or temporal topic of the resource, the spatial applicability of the resource, or the jurisdiction under which the resource is relevant</description>
            <elementTextContainer>
              <elementText elementTextId="4302">
                <text>Biology (General), Immunologic diseases. Allergy</text>
              </elementText>
            </elementTextContainer>
          </element>
          <element elementId="44">
            <name>Language</name>
            <description>A language of the resource</description>
            <elementTextContainer>
              <elementText elementTextId="4303">
                <text>EN</text>
              </elementText>
            </elementTextContainer>
          </element>
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        <src>https://www.socictopen.socict.org/files/original/30525ad1d0b310f2c8d623858d961fb4.pdf</src>
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          <name>Dublin Core</name>
          <description>The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.</description>
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            <element elementId="50">
              <name>Title</name>
              <description>A name given to the resource</description>
              <elementTextContainer>
                <elementText elementTextId="1">
                  <text>Coronavirus</text>
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              </elementTextContainer>
            </element>
            <element elementId="41">
              <name>Description</name>
              <description>An account of the resource</description>
              <elementTextContainer>
                <elementText elementTextId="2">
                  <text>Dominio científico: Coronavirus</text>
                </elementText>
              </elementTextContainer>
            </element>
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    </collection>
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      <name>Text</name>
      <description>A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.</description>
    </itemType>
    <elementSetContainer>
      <elementSet elementSetId="1">
        <name>Dublin Core</name>
        <description>The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.</description>
        <elementContainer>
          <element elementId="50">
            <name>Title</name>
            <description>A name given to the resource</description>
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              <elementText elementTextId="4304">
                <text>Targeting membrane-bound viral RNA synthesis reveals potent inhibition of diverse coronaviruses including the middle East respiratory syndrome virus.</text>
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          <element elementId="39">
            <name>Creator</name>
            <description>An entity primarily responsible for making the resource</description>
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              <elementText elementTextId="4305">
                <text>Anna Lundin, Ronald Dijkman, Tomas Bergström, Nina Kann, Beata Adamiak, Charles Hannoun, Eveline Kindler, Hulda  R. Jonsdottir, Doreen Muth, Joeri Kint, Maria Forlenza, Marcel A. Müller, Christian Drosten, Volker Thiel, Edward Trybala</text>
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          <element elementId="41">
            <name>Description</name>
            <description>An account of the resource</description>
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              <elementText elementTextId="4306">
                <text>Coronaviruses raise serious concerns as emerging zoonotic viruses without specific antiviral drugs available. Here we screened a collection of 16671 diverse compounds for anti-human coronavirus 229E activity and identified an inhibitor, designated K22, that specifically targets membrane-bound coronaviral RNA synthesis. K22 exerts most potent antiviral activity after virus entry during an early step of the viral life cycle. Specifically, the formation of double membrane vesicles (DMVs), a hallmark of coronavirus replication, was greatly impaired upon K22 treatment accompanied by near-complete inhibition of viral RNA synthesis. K22-resistant viruses contained substitutions in non-structural protein 6 (nsp6), a membrane-spanning integral component of the viral replication complex implicated in DMV formation, corroborating that K22 targets membrane bound viral RNA synthesis. Besides K22 resistance, the nsp6 mutants induced a reduced number of DMVs, displayed decreased specific infectivity, while RNA synthesis was not affected. Importantly, K22 inhibits a broad range of coronaviruses, including Middle East respiratory syndrome coronavirus (MERS-CoV), and efficient inhibition was achieved in primary human epithelia cultures representing the entry port of human coronavirus infection. Collectively, this study proposes an evolutionary conserved step in the life cycle of positive-stranded RNA viruses, the recruitment of cellular membranes for viral replication, as vulnerable and, most importantly, druggable target for antiviral intervention. We expect this mode of action to serve as a paradigm for the development of potent antiviral drugs to combat many animal and human virus infections.</text>
              </elementText>
            </elementTextContainer>
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          <element elementId="40">
            <name>Date</name>
            <description>A point or period of time associated with an event in the lifecycle of the resource</description>
            <elementTextContainer>
              <elementText elementTextId="4307">
                <text>2014</text>
              </elementText>
            </elementTextContainer>
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          <element elementId="43">
            <name>Identifier</name>
            <description>An unambiguous reference to the resource within a given context</description>
            <elementTextContainer>
              <elementText elementTextId="4308">
                <text>DOI: 10.1371/journal.ppat.1004166</text>
              </elementText>
            </elementTextContainer>
          </element>
          <element elementId="48">
            <name>Source</name>
            <description>A related resource from which the described resource is derived</description>
            <elementTextContainer>
              <elementText elementTextId="4309">
                <text>PLoS Pathogens</text>
              </elementText>
            </elementTextContainer>
          </element>
          <element elementId="45">
            <name>Publisher</name>
            <description>An entity responsible for making the resource available</description>
            <elementTextContainer>
              <elementText elementTextId="4310">
                <text>Public Library of Science (PLoS)</text>
              </elementText>
            </elementTextContainer>
          </element>
          <element elementId="38">
            <name>Coverage</name>
            <description>The spatial or temporal topic of the resource, the spatial applicability of the resource, or the jurisdiction under which the resource is relevant</description>
            <elementTextContainer>
              <elementText elementTextId="4311">
                <text>Biology (General), Immunologic diseases. Allergy</text>
              </elementText>
            </elementTextContainer>
          </element>
          <element elementId="44">
            <name>Language</name>
            <description>A language of the resource</description>
            <elementTextContainer>
              <elementText elementTextId="4312">
                <text>EN</text>
              </elementText>
            </elementTextContainer>
          </element>
        </elementContainer>
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  </item>
</itemContainer>
