The molecular mechanisms that drive the infection by the SARS-CoV-2 coronavirus, the causative agent of the COVID-19 (Coronavirus disease-2019) pandemic, are under intense current scrutiny, to understand how the virus operates and to uncover ways in which the disease can be prevented or alleviated. Recent cell-based analyses of SARS-CoV-2 protein - protein interactions have mapped the human proteins targeted by the virus. The DNA polymerase α - primase complex or primosome, responsible for initiating DNA synthesis in genomic duplication, was identified as a target of nsp1 (non structural protein 1), a major virulence factor in the SARS-CoV-2 infection. Here, we report the biochemical characterisation of the interaction between nsp1 and the primosome and the cryoEM structure of the primosome - nsp1 complex. Our data provide a structural basis for the reported interaction between the primosome and nsp1. They suggest that Pol α - primase plays a part in the immune response to the viral infection, and that its targeting by SARS-CoV-2 aims to interfere with such function.

中文翻译：

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SARS-CoV-2毒力因子nsp1与Pol α-Primase相互作用的结构基础

SARS-CoV-2 冠状病毒感染的分子机制是 COVID-19（冠状病毒病-2019）大流行的病原体，目前正受到严格​​审查，以了解该病毒的运作方式并揭示其传播途径。这种疾病是可以预防或减轻的。最近对 SARS-CoV-2 蛋白质-蛋白质相互作用的基于细胞的分析已经绘制了病毒靶向的人类蛋白质的图谱。DNA 聚合酶 α-引物酶复合物或原体，负责在基因组复制中启动 DNA 合成，被确定为 nsp1（非结构蛋白 1）的靶标，它是 SARS-CoV-2 感染的主要毒力因子。在这里，我们报告了 nsp1 和 primosome 之间相互作用的生化表征以及 primosome-nsp1 复合物的冷冻电镜结构。我们的数据为所报道的primosome 和nsp1 之间的相互作用提供了结构基础。他们认为 Pol α - primase 在对病毒感染的免疫反应中起作用，而 SARS-CoV-2 的目标是干扰这种功能。