Characterization of accessory genes in coronavirus genomes
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RESEARCH
Open Access
Characterization of accessory genes in coronavirus genomes Christian Jean Michel1, Claudine Mayer1,2,3, Olivier Poch1 and Julie Dawn Thompson1*
Abstract Background: The Covid19 infection is caused by the SARS-CoV-2 virus, a novel member of the coronavirus (CoV) family. CoV genomes code for a ORF1a / ORF1ab polyprotein and four structural proteins widely studied as major drug targets. The genomes also contain a variable number of open reading frames (ORFs) coding for accessory proteins that are not essential for virus replication, but appear to have a role in pathogenesis. The accessory proteins have been less well characterized and are difficult to predict by classical bioinformatics methods. Methods: We propose a computational tool GOFIX to characterize potential ORFs in virus genomes. In particular, ORF coding potential is estimated by searching for enrichment in motifs of the X circular code, that is known to be over-represented in the reading frames of viral genes. Results: We applied GOFIX to study the SARS-CoV-2 and related genomes including SARS-CoV and SARS-like viruses from bat, civet and pangolin hosts, focusing on the accessory proteins. Our analysis provides evidence supporting the presence of overlapping ORFs 7b, 9b and 9c in all the genomes and thus helps to resolve some differences in current genome annotations. In contrast, we predict that ORF3b is not functional in all genomes. Novel putative ORFs were also predicted, including a truncated form of the ORF10 previously identified in SARSCoV-2 and a little known ORF overlapping the Spike protein in Civet-CoV and SARS-CoV. Conclusions: Our findings contribute to characterizing sequence properties of accessory genes of SARS coronaviruses, and especially the newly acquired genes making use of overlapping reading frames. Keywords: COVID-19, SARS-CoV-2, SARS-CoV, Coronavirus, Accessory genes, ORF prediction, Circular code motifs
Background Coronaviruses (CoVs) cause respiratory and intestinal infections in animals and humans [1]. They were not considered to be highly pathogenic to humans until the last two decades, which have seen three outbreaks of highly transmissible and pathogenic coronaviruses, including SARS-CoV (severe acute respiratory syndrome coronavirus), MERS-CoV (Middle East respiratory syndrome coronavirus), and SARS-CoV-2 (which causes the disease COVID-19). Other human coronaviruses (such as HCoV-NL63, HCoV-229E, HCoV-OC43 or HKU1) * Correspondence: [email protected] 1 Laboratoire ICube, Department of Computer Science, CNRS, University of Strasbourg, F-67412 Strasbourg, France Full list of author information is available at the end of the article
generally induce only mild upper respiratory diseases in immunocompetent hosts, although some may cause severe infections in infants, young children and elderly individuals [1]. Extensive studies of human coronaviruses have led to a better understanding of coronavirus biology. Coronaviruses belong to the family Coronaviridae in the order nidovirales. Whereas MERS-CoV is
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