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1 Institute of Virology and Immunology, University of Würzburg, Würzburg, Germany
2 Research Department, Cantonal Hospital St Gallen, CH-9007 St Gallen, Switzerland
3 Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, Bristol, UK
Correspondence
Volker Thiel
volker.thiel{at}kssg.ch
A previously unknown coronavirus (CoV) is the aetiological agent causing severe acute respiratory syndrome (SARS), for which an effective antiviral treatment is urgently needed. To enable the rapid and biosafe identification of coronavirus replicase inhibitors, we have generated a non-cytopathic, selectable replicon RNA (based on human CoV 229E) that can be stably maintained in eukaryotic cells. Most importantly, the replicon RNA mediates reporter gene expression as a marker for coronavirus replication. We have used a replicon RNA-containing cell line to test the inhibitory effect of several compounds that are currently being assessed for SARS treatment. Amongst those, interferon-
displayed the strongest inhibitory activity. Our results demonstrate that coronavirus replicon cell lines provide a versatile and safe assay for the identification of coronavirus replicase inhibitors. Once this technology is adapted to SARS-CoV replicon RNAs, it will allow high throughput screening for SARS-CoV replicase inhibitors without the need to grow infectious SARS-CoV.
T. H. and E. S. contributed equally to this work.
Published online ahead of print on 19 March 2004 as DOI 10.1099/vir.0.80044-0.
This article has been cited by other articles:
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R. Zust, T. B. Miller, S. J. Goebel, V. Thiel, and P. S. Masters Genetic Interactions between an Essential 3' cis-Acting RNA Pseudoknot, Replicase Gene Products, and the Extreme 3' End of the Mouse Coronavirus Genome J. Virol., February 1, 2008; 82(3): 1214 - 1228. [Abstract] [Full Text] [PDF]
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J. Ziebuhr, B. Schelle, N. Karl, E. Minskaia, S. Bayer, S. G. Siddell, A. E. Gorbalenya, and V. Thiel Human Coronavirus 229E Papain-Like Proteases Have Overlapping Specificities but Distinct Functions in Viral Replication J. Virol., April 15, 2007; 81(8): 3922 - 3932. [Abstract] [Full Text] [PDF]
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 E. van den Born, C. C. Posthuma, K. Knoops, and E. J. Snijder An infectious recombinant equine arteritis virus expressing green fluorescent protein from its replicase gene J. Gen. Virol., April 1, 2007; 88(4): 1196 - 1205. [Abstract] [Full Text] [PDF]
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H. Schutze, R. Ulferts, B. Schelle, S. Bayer, H. Granzow, B. Hoffmann, T. C. Mettenleiter, and J. Ziebuhr Characterization of White Bream Virus Reveals a Novel Genetic Cluster of Nidoviruses J. Virol., December 1, 2006; 80(23): 11598 - 11609. [Abstract] [Full Text] [PDF]
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R. L. Graham, A. C. Sims, S. M. Brockway, R. S. Baric, and M. R. Denison The nsp2 Replicase Proteins of Murine Hepatitis Virus and Severe Acute Respiratory Syndrome Coronavirus Are Dispensable for Viral Replication J. Virol., November 1, 2005; 79(21): 13399 - 13411. [Abstract] [Full Text] [PDF]
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A. Putics, W. Filipowicz, J. Hall, A. E. Gorbalenya, and J. Ziebuhr ADP-Ribose-1"-Monophosphatase: a Conserved Coronavirus Enzyme That Is Dispensable for Viral Replication in Tissue Culture J. Virol., October 15, 2005; 79(20): 12721 - 12731. [Abstract] [Full Text] [PDF]
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B. Schelle, N. Karl, B. Ludewig, S. G. Siddell, and V. Thiel Selective Replication of Coronavirus Genomes That Express Nucleocapsid Protein J. Virol., June 1, 2005; 79(11): 6620 - 6630. [Abstract] [Full Text] [PDF]
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L. Chen, C. Gui, X. Luo, Q. Yang, S. Gunther, E. Scandella, C. Drosten, D. Bai, X. He, B. Ludewig, et al. Cinanserin Is an Inhibitor of the 3C-Like Proteinase of Severe Acute Respiratory Syndrome Coronavirus and Strongly Reduces Virus Replication In Vitro J. Virol., June 1, 2005; 79(11): 7095 - 7103. [Abstract] [Full Text] [PDF]
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S. E. Coley, E. Lavi, S. G. Sawicki, L. Fu, B. Schelle, N. Karl, S. G. Siddell, and V. Thiel Recombinant Mouse Hepatitis Virus Strain A59 from Cloned, Full-Length cDNA Replicates to High Titers In Vitro and Is Fully Pathogenic In Vivo J. Virol., March 1, 2005; 79(5): 3097 - 3106. [Abstract] [Full Text] [PDF]
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