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

Matthias Thoms | Zendy; Robert Buschauer | Zendy; Michael Ameismeier | Zendy; Lennart Koepke | Zendy; Timo Denk | Zendy; Maximilian Hirschenberger | Zendy; Hanna Kratzat | Zendy; Manuel Hayn | Zendy; Timur MackensKiani | Zendy; Jingdong Cheng | Zendy; Jan Hendrik Straub | Zendy; Christina M. Stürzel | Zendy; Thomas Fröhlich | Zendy; Otto Berninghausen | Zendy; Thomas Becker | Zendy; Frank Kirchhoff | Zendy; Konstantin M. J. Sparrer | Zendy; Roland Beckmann | Zendy

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

Author(s) -

Matthias Thoms,

Robert Buschauer,

Michael Ameismeier,

Lennart Koepke,

Timo Denk,

Maximilian Hirschenberger,

Hanna Kratzat,

Manuel Hayn,

Timur MackensKiani,

Jingdong Cheng,

Jan Hendrik Straub,

Christina M. Stürzel,

Thomas Fröhlich,

Otto Berninghausen,

Thomas Becker,

Frank Kirchhoff,

Konstantin M. J. Sparrer,

Roland Beckmann

Publication year - 2020

Publication title -

science

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 12.556

H-Index - 1186

eISSN - 1095-9203

pISSN - 0036-8075

DOI - 10.1126/science.abc8665

Subject(s) - shutdown , covid-19 , evasion (ethics) , virology , immune escape , immune system , biology , immunology , medicine , engineering , nuclear engineering , disease , pathology , infectious disease (medical specialty) , outbreak

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current coronavirus disease 2019 (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 40 S ribosomal subunit, resulting in shutdown of messenger RNA (mRNA) translation both in vitro and in cells. Structural analysis by cryo-electron microscopy of in vitro-reconstituted Nsp1-40 S and various native Nsp1-40 S and -80 S complexes revealed that the Nsp1 C terminus binds to and obstructs the mRNA entry tunnel. Thereby, Nsp1 effectively blocks retinoic acid-inducible gene 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.

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