We identified 11 conserved stretches in over 6.3 million SARS-CoV-2 genomes including all the major variants of concerns. Each conserved stretch is ≥100 nucleotides in length with ≥99.9% conservation at each nucleotide position. Interestingly, six of the eight conserved stretches in ORF1ab overlapped significantly with well-folded experimentally verified RNA secondary structures. Furthermore, two of the conserved stretches were mapped to regions within the S2-subunit that undergo dynamic structural rearrangements during viral fusion. In addition, the conserved stretches were significantly depleted for zinc-finger antiviral protein (ZAP) binding sites, which facilitated the recognition and degradation of viral RNA. These highly conserved stretches in the SARS-CoV-2 genome were poorly conserved at the nucleotide level among closely related β-coronaviruses, thus representing ideal targets for highly specific and discriminatory diagnostic assays. Our findings highlight the role of structural constraints at both RNA and protein levels that contribute to the sequence conservation of specific genomic regions in SARS-CoV-2.

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绘制超过 600 万个 SARS-CoV-2 基因组中长段高度保守序列的图谱

我们在超过 630 万个 SARS-CoV-2 基因组中确定了 11 个保守片段，包括所有值得关注的主要变体。每个保守片段的长度≥100个核苷酸，每个核苷酸位置的保守性≥99.9%。有趣的是，ORF1ab 中 8 个保守片段中的 6 个与实验验证的折叠良好的 RNA 二级结构显着重叠。此外，两个保守的片段被映射到 S2 亚基内的区域，这些区域在病毒融合过程中经历动态结构重排。此外，保守片段的锌指抗病毒蛋白（ZAP）结合位点显着减少，这有利于病毒RNA的识别和降解。SARS-CoV-2 基因组中的这些高度保守的片段在密切相关的 β 冠状病毒中在核苷酸水平上保守性很差，因此代表了高度特异性和歧视性诊断分析的理想靶标。我们的研究结果强调了 RNA 和蛋白质水平上的结构限制的作用，这些限制有助于 SARS-CoV-2 中特定基因组区域的序列保守。