德国慕尼黑大学Roland Beckmann、乌尔姆大学Konstantin M. J. Sparrer等研究人员合作，揭示了SARS-CoV-2 Nsp1蛋白对翻译关闭和免疫逃避的结构基础。相关论文于2020年7月17日在线发表于《科学》。

Title: Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2

Author: Matthias Thoms, Robert Buschauer, Michael Ameismeier, Lennart Koepke, Timo Denk, Maximilian Hirschenberger, Hanna Kratzat, Manuel Hayn, Timur Mackens-Kiani, Jingdong Cheng, Jan H. Straub, Christina M. Stürzel, Thomas Frhlich, Otto Berninghausen, Thomas Becker, Frank Kirchhoff, Konstantin M. J. Sparrer, Roland Beckmann

Issue&Volume: 2020/07/17

Abstract: Abstract SARS-CoV-2 is the causative agent of the current COVID-19 pandemic. A major virulence factor of SARS-CoVs is the nonstructural protein 1 (Nsp1) which suppresses host gene expression by ribosome association. Here, we show that Nsp1 from SARS-CoV-2 binds to the 40S ribosomal subunit, resulting in shutdown of mRNA translation both in vitro and in cells. Structural analysis by cryo-electron microscopy (cryo-EM) of in vitro reconstituted Nsp1-40S and various native Nsp1-40S and -80S complexes revealed that the Nsp1 C terminus binds to and obstructs the mRNA entry tunnel. Thereby, Nsp1 effectively blocks RIG-I-dependent innate immune responses that would otherwise facilitate clearance of the infection. Thus, the structural characterization of the inhibitory mechanism of Nsp1 may aid structure-based drug design against SARS-CoV-2.

DOI: 10.1126/science.abc8665

Source: https://science.sciencemag.org/content/early/2020/07/16/science.abc8665