Coronavirus 3CLpro proteinase cleavage sites Possible relevance to SARS virus pathology.docVIP

BMC Bioinformatics BioMedCentral Methodology article Open Access Coronavirus 3CLpro proteinase cleavage sites: Possible relevance to SARS virus pathology Lars Kiemer, Ole Lund, S?ren Brunak and Nikolaj Blom* Address: Center for Biological Sequence Analysis BioCentrum-DTU, Building 208 Technical University of Denmark DK-2800 Lyngby, Denmark Email: Lars Kiemer - lars@cbs.dtu.dk; Ole Lund - lund@cbs.dtu.dk; S?ren Brunak - brunak@cbs.dtu.dk; Nikolaj Blom* - nikob@cbs.dtu.dk * Corresponding author Published: 06 June 2004 Received: 23 January 2004 Accepted: 06 June 2004 BMC Bioinformatics 2004, 5:72 This article is available from: /1471-2105/5/72 ? 2004 Kiemer et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the articles original URL. Abstract Background: Despite the passing of more than a year since the first outbreak of Severe Acute Respiratory Syndrome (SARS), efficient counter-measures are still few and many believe that reappearance of SARS, or a similar disease caused by a coronavirus, is not unlikely. For other virus families like the picornaviruses it is known that pathology is related to proteolytic cleavage of host proteins by viral proteinases. Furthermore, several studies indicate that virus proliferation can be arrested using specific proteinase inhibitors supporting the belief that proteinases are indeed important during infection. Prompted by this, we set out to analyse and predict cleavage by the coronavirus main proteinase using computational methods. Results: We retrieved sequence data on seven fully sequenced coronaviruses and identified the main 3CL proteinase cleavage sites in polyproteins using alignments. A neural network was trained to recognise the cleavage sites in the genomes obtaining a sensitivity of 87.0% and a specifici