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. 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. 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 SARS-CoV-2 and a little known ORF overlapping the Spike protein in Civet-CoV and SARS-CoV. 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.

中文翻译：

---

冠状病毒基因组中辅助基因的表征。


Covid19 感染是由 SARS-CoV-2 病毒引起的，它是冠状病毒 (CoV) 家族的新成员。冠状病毒基因组编码 ORF1a / ORF1ab 多蛋白和四种结构蛋白，作为主要药物靶点被广泛研究。基因组还包含数量可变的开放阅读框（ORF），编码辅助蛋白，这些蛋白对于病毒复制不是必需的，但似乎在发病机制中发挥作用。辅助蛋白的特征还不太清楚，并且很难通过经典的生物信息学方法进行预测。我们提出了一种计算工具 GOFIX 来表征病毒基因组中潜在的 ORF。特别是，ORF编码潜力是通过寻找X环形密码基序的富集来估计的，已知该基序在病毒基因的阅读框中过度呈现。我们应用 GOFIX 研究 SARS-CoV-2 和相关基因组，包括来自蝙蝠、果子狸和穿山甲宿主的 SARS-CoV 和 SARS 样病毒，重点关注辅助蛋白。我们的分析提供了支持所有基因组中存在重叠 ORF 7b、9b 和 9c 的证据，从而有助于解决当前基因组注释中的一些差异。相比之下，我们预测 ORF3b 并非在所有基因组中都有功能。还预测了新的假定 ORF，包括先前在 SARS-CoV-2 中发现的 ORF10 的截短形式，以及鲜为人知的与果子狸-CoV 和 SARS-CoV 中的 Spike 蛋白重叠的 ORF。我们的研究结果有助于表征 SARS 冠状病毒辅助基因的序列特性，特别是利用重叠阅读框的新获得基因。