Mechanisms and enzymes involved in SARS coronavirus genome expression.
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.
Thiel
Volker
V
Institute of Virology and Immunology, University of Würzburg, Versbacher Str. 7, 97078 Würzburg, Germany.
Ivanov
Konstantin A
KA
Institute of Virology and Immunology, University of Würzburg, Versbacher Str. 7, 97078 Würzburg, Germany.
Putics
Ákos
Á
Institute of Virology and Immunology, University of Würzburg, Versbacher Str. 7, 97078 Würzburg, Germany.
Hertzig
Tobias
T
Institute of Virology and Immunology, University of Würzburg, Versbacher Str. 7, 97078 Würzburg, Germany.
Schelle
Barbara
B
Institute of Virology and Immunology, University of Würzburg, Versbacher Str. 7, 97078 Würzburg, Germany.
Bayer
Sonja
S
Institute of Virology and Immunology, University of Würzburg, Versbacher Str. 7, 97078 Würzburg, Germany.
Weißbrich
Benedikt
B
Institute of Virology and Immunology, University of Würzburg, Versbacher Str. 7, 97078 Würzburg, Germany.
Snijder
Eric J
EJ
Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
Rabenau
Holger
H
Institute for Medical Virology, Johann Wolfgang Goethe University, Frankfurt (Main), Germany.
Doerr
Hans Wilhelm
HW
Institute for Medical Virology, Johann Wolfgang Goethe University, Frankfurt (Main), Germany.
Gorbalenya
Alexander E
AE
Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
Ziebuhr
John
J
Institute of Virology and Immunology, University of Würzburg, Versbacher Str. 7, 97078 Würzburg, Germany.
D000595:Amino Acid Sequence; D020134:Catalytic Domain; D000086782:Coronavirus 3C Proteases; D000086882:Coronavirus Papain-Like Proteases; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism; D018965:Frameshifting, Ribosomal; D015967:Gene Expression Regulation, Viral; D016679:Genome, Viral; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010206:Papain / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis; D020365:RNA Helicases / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D045473:Severe acute respiratory syndrome-related coronavirus / Q000201:enzymology / Q000235:genetics* / Q000302:isolation & purification; D016415:Sequence Alignment; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism
D012333:RNA, Messenger; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D000086882:Coronavirus Papain-Like Proteases; D010206:Papain; C000706268:papain-like protease, SARS coronavirus; D000086782:Coronavirus 3C Proteases; D020365:RNA Helicases