论文标题

SARS-COV-2的结构分析和人类互动组的预测

Structural analysis of SARS-CoV-2 and prediction of the human interactome

论文作者

Vandelli, Andrea, Monti, Michele, Milanetti, Edoardo, Ponti, Riccardo Delli, Tartaglia, Gian Gaetano

论文摘要

病毒基因组的特定元素调节宿主细胞内的相互作用。在这里,我们计算了> 2500个冠状病毒的二级结构含量,并计算出与严重急性呼吸综合征冠状病毒2(SARS-COV-2)的人类蛋白质相互作用。我们发现,3和5质量末端是病毒基因组中最结构化的元素,而5个质子端具有与人蛋白相关的最强倾向。包含核苷酸23000-24000的结构域在序列和结构水平上都是高度保守的,而该区域上游的变化很大。这两个序列代码为病毒蛋白峰的结构域与人类受体血管紧张素转换酶2(ACE2)相互作用,并且具有结合唾液酸的潜力。我们的预测表明,除其他高信任候选伴侣外,5个质子端中的前1000个核苷酸还可以与参与病毒RNA加工的蛋白质相互作用,例如双链RNA特异性编辑酶和ATP依赖性RNA-螺旋酶。这些相互作用以前据报道也与HIV有关,揭示了有关宿主病毒相互作用的重要信息。 SARS-COV-2基因组募集的转录和转录后元件列表提供了与人类细胞基因表达变化相关的生物学途径的线索。

Specific elements of viral genomes regulate interactions within host cells. Here, we calculated the secondary structure content of >2500 coronaviruses and computed >100000 human protein interactions with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We found that the 3 and 5 prime ends are the most structured elements in the viral genome and the 5 prime end has the strongest propensity to associate with human proteins. The domain encompassing nucleotides 23000-24000 is highly conserved both at the sequence and structural level, while the region upstream varies significantly. These two sequences code for a domain of the viral protein Spike S that interacts with the human receptor angiotensin-converting enzyme 2 (ACE2) and has the potential to bind sialic acids. Our predictions indicate that the first 1000 nucleotides in the 5 prime end can interact with proteins involved in viral RNA processing such as double-stranded RNA specific editases and ATP-dependent RNA-helicases, in addition to other high-confidence candidate partners. These interactions, previously reported to be also implicated in HIV, reveal important information on host-virus interactions. The list of transcriptional and post-transcriptional elements recruited by SARS-CoV-2 genome provides clues on the biological pathways associated with gene expression changes in human cells.

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