Nonstructural protein 1 of SARS-CoV-2 is a potent pathogenicity factor redirecting host protein synthesis machinery toward viral RNA

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses its nonstructural protein 1 (Nsp1) to redirect host translation machinery to the viral RNA by binding to the ribosome and suppressing cellular, but not viral, protein synthesis through yet unknown mechanisms. We show here that among all viral proteins, Nsp1 has the largest impact on host viability in the cells of human lung origin. Results presented here including mRNA-seq and cryo-EM data elucidate the mechanism of host translation inhibition by SARS-CoV-2, provide insight into viral protein synthesis, and furnish a comprehensive understanding of the impacts from one of the most potent pathogenicity factors of SARS-CoV-2.严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）通过其非结构蛋白1（Nsp1）结合核糖体，将宿主翻译机器重定向至病毒RNA，并通过尚未阐明的机制抑制宿主细胞而非病毒的蛋白质合成。本研究证实，在所有病毒蛋白中，Nsp1对人源肺细胞的宿主细胞活力影响最大。本研究展示的结果包括信使RNA测序（mRNA-seq）与冷冻电镜（cryo-EM）数据，这些数据阐明了SARS-CoV-2介导的宿主翻译抑制机制，为病毒蛋白质合成研究提供了新见解，并全面阐释了SARS-CoV-2最强效致病因子之一所产生的影响。