Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic 1 . To understand the pathogenicity and antigenic potential of SARS-CoV-2 and to develop therapeutic tools, it is essential to profile the full repertoire of its expressed proteins. The current map of SARS-CoV-2 coding capacity is based on computational predictions and relies on homology with other coronaviruses. As the protein complement varies among coronaviruses, especially in regard to the variety of accessory proteins, it is crucial to characterize the specific range of SARS-CoV-2 proteins in an unbiased and open-ended manner. Here, using a suite of ribosome-profiling techniques 2 – 4 , we present a high-resolution map of coding regions in the SARS-CoV-2 genome, which enables us to accurately quantify the expression of canonical viral open reading frames (ORFs) and to identify 23 unannotated viral ORFs. These ORFs include upstream ORFs that are likely to have a regulatory role, several in-frame internal ORFs within existing ORFs, resulting in N-terminally truncated products, as well as internal out-of-frame ORFs, which generate novel polypeptides. We further show that viral mRNAs are not translated more efficiently than host mRNAs; instead, virus translation dominates host translation because of the high levels of viral transcripts. Our work provides a resource that will form the basis of future functional studies. A high-resolution map of coding regions in the SARS-CoV-2 genome enables the identification of 23 unannotated open reading frames and quantification of the expression of canonical viral open reading frames.

中文翻译：

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SARS-CoV-2的编码能力

严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 是导致 2019 年冠状病毒病 (COVID-19) 大流行 1 的原因。为了了解 SARS-CoV-2 的致病性和抗原潜力并开发治疗工具，必须对其表达的蛋白质的完整库进行分析。当前的 SARS-CoV-2 编码能力图基于计算预测，并依赖于与其他冠状病毒的同源性。由于不同冠状病毒的蛋白质补体各不相同，特别是在辅助蛋白的种类方面，因此以公正和开放的方式表征 SARS-CoV-2 蛋白质的特定范围至关重要。在这里，我们使用一套核糖体分析技术 2 - 4，展示了 SARS-CoV-2 基因组中编码区的高分辨率图谱，这使我们能够准确量化规范病毒开放阅读框 (ORF) 的表达并识别 23 个未注释的病毒 ORF。这些 ORF 包括可能具有调节作用的上游 ORF、现有 ORF 中的几个框内内部 ORF，导致 N 端截短的产物，以及内部框外 ORF，它们产生新的多肽。我们进一步表明，病毒 mRNA 的翻译效率并不比宿主 mRNA 高。相反，由于高水平的病毒转录本，病毒翻译在宿主翻译中占主导地位。我们的工作提供了一种资源，将构成未来功能研究的基础。