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Mechanisms and enzymes involved in SARS coronavirus genome expression.

Identifieur interne : 003223 ( PubMed/Curation ); précédent : 003222; suivant : 003224

Mechanisms and enzymes involved in SARS coronavirus genome expression.

Auteurs : Volker Thiel [Allemagne] ; Konstantin A. Ivanov [Allemagne] ; Ákos Putics [Allemagne] ; Tobias Hertzig [Allemagne] ; Barbara Schelle [Allemagne] ; Sonja Bayer [Allemagne] ; Benedikt Wei Brich [Allemagne] ; Eric J. Snijder [Pays-Bas] ; Holger Rabenau [Allemagne] ; Hans Wilhelm Doerr [Allemagne] ; Alexander E. Gorbalenya [Pays-Bas] ; John Ziebuhr [Allemagne]

Source :

RBID : pubmed:12917450

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English descriptors

Abstract

A novel coronavirus is the causative agent of the current epidemic of severe acute respiratory syndrome (SARS). Coronaviruses are exceptionally large RNA viruses and employ complex regulatory mechanisms to express their genomes. Here, we determined the sequence of SARS coronavirus (SARS-CoV), isolate Frankfurt 1, and characterized key RNA elements and protein functions involved in viral genome expression. Important regulatory mechanisms, such as the (discontinuous) synthesis of eight subgenomic mRNAs, ribosomal frameshifting and post-translational proteolytic processing, were addressed. Activities of three SARS coronavirus enzymes, the helicase and two cysteine proteinases, which are known to be critically involved in replication, transcription and/or post-translational polyprotein processing, were characterized. The availability of recombinant forms of key replicative enzymes of SARS coronavirus should pave the way for high-throughput screening approaches to identify candidate inhibitors in compound libraries.

DOI: 10.1099/vir.0.19424-0
PubMed: 12917450

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Le document en format XML

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<div type="abstract" xml:lang="en">A novel coronavirus is the causative agent of the current epidemic of severe acute respiratory syndrome (SARS). Coronaviruses are exceptionally large RNA viruses and employ complex regulatory mechanisms to express their genomes. Here, we determined the sequence of SARS coronavirus (SARS-CoV), isolate Frankfurt 1, and characterized key RNA elements and protein functions involved in viral genome expression. Important regulatory mechanisms, such as the (discontinuous) synthesis of eight subgenomic mRNAs, ribosomal frameshifting and post-translational proteolytic processing, were addressed. Activities of three SARS coronavirus enzymes, the helicase and two cysteine proteinases, which are known to be critically involved in replication, transcription and/or post-translational polyprotein processing, were characterized. The availability of recombinant forms of key replicative enzymes of SARS coronavirus should pave the way for high-throughput screening approaches to identify candidate inhibitors in compound libraries.</div>
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<AffiliationInfo>
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<Author ValidYN="Y">
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<Initials>B</Initials>
<AffiliationInfo>
<Affiliation>Institute of Virology and Immunology, University of Würzburg, Versbacher Str. 7, 97078 Würzburg, Germany.</Affiliation>
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<ForeName>Holger</ForeName>
<Initials>H</Initials>
<AffiliationInfo>
<Affiliation>Institute for Medical Virology, Johann Wolfgang Goethe University, Frankfurt (Main), Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Doerr</LastName>
<ForeName>Hans Wilhelm</ForeName>
<Initials>HW</Initials>
<AffiliationInfo>
<Affiliation>Institute for Medical Virology, Johann Wolfgang Goethe University, Frankfurt (Main), Germany.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Gorbalenya</LastName>
<ForeName>Alexander E</ForeName>
<Initials>AE</Initials>
<AffiliationInfo>
<Affiliation>Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.</Affiliation>
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</Author>
<Author ValidYN="Y">
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<Initials>J</Initials>
<AffiliationInfo>
<Affiliation>Institute of Virology and Immunology, University of Würzburg, Versbacher Str. 7, 97078 Würzburg, Germany.</Affiliation>
</AffiliationInfo>
</Author>
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<Country>England</Country>
<MedlineTA>J Gen Virol</MedlineTA>
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<ISSNLinking>0022-1317</ISSNLinking>
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</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
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<Chemical>
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<Chemical>
<RegistryNumber>EC 3.4.22.2</RegistryNumber>
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<Chemical>
<RegistryNumber>EC 3.6.4.13</RegistryNumber>
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<MeshHeading>
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<MeshHeading>
<DescriptorName UI="D003546" MajorTopicYN="N">Cysteine Endopeptidases</DescriptorName>
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<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D018965" MajorTopicYN="N">Frameshifting, Ribosomal</DescriptorName>
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<MeshHeading>
<DescriptorName UI="D015967" MajorTopicYN="Y">Gene Expression Regulation, Viral</DescriptorName>
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<MeshHeading>
<DescriptorName UI="D016679" MajorTopicYN="Y">Genome, Viral</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D008969" MajorTopicYN="N">Molecular Sequence Data</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D009690" MajorTopicYN="N">Nucleic Acid Conformation</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D010206" MajorTopicYN="N">Papain</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D014176" MajorTopicYN="N">Protein Biosynthesis</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D020365" MajorTopicYN="N">RNA Helicases</DescriptorName>
<QualifierName UI="Q000096" MajorTopicYN="N">biosynthesis</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D012333" MajorTopicYN="N">RNA, Messenger</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D045473" MajorTopicYN="N">SARS Virus</DescriptorName>
<QualifierName UI="Q000201" MajorTopicYN="N">enzymology</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName>
<QualifierName UI="Q000302" MajorTopicYN="N">isolation & purification</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D016415" MajorTopicYN="N">Sequence Alignment</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D014764" MajorTopicYN="N">Viral Proteins</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
</MeshHeadingList>
</MedlineCitation>
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<Year>2003</Year>
<Month>8</Month>
<Day>15</Day>
<Hour>5</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline">
<Year>2003</Year>
<Month>10</Month>
<Day>17</Day>
<Hour>5</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez">
<Year>2003</Year>
<Month>8</Month>
<Day>15</Day>
<Hour>5</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
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<ArticleId IdType="pubmed">12917450</ArticleId>
<ArticleId IdType="doi">10.1099/vir.0.19424-0</ArticleId>
</ArticleIdList>
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