Molecular Basis of SARS-CoV-2 Nsp1-Induced Immune Translational Shutdown as Revealed by All-Atom Simulations

被引：6

作者：

Borisek, Jure ^{[1
]}

Spinello, Angelo ^{[2
]}

Magistrato, Alessandra ^{[2
]}

机构：

[1] Natl Inst Chem, Ljubljana 1001, Slovenia

[2] SISSA, CNR IOM Democritos Natl Simulat Ctr, I-34136 Trieste, Italy

来源：

JOURNAL OF PHYSICAL CHEMISTRY LETTERS | 2021年 / 12卷 / 48期

关键词：

Coronavirus;

D O I：

10.1021/acs.jpclett.1c03441

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070304 ; 081704 ;

摘要：

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic represents the most severe global health crisis in modern human history. One of the major SARS-CoV-2 virulence factors is nonstructural protein 1 (Nsp1), which, outcompeting with the binding of host mRNA to the human ribosome, triggers a translation shutdown of the host immune system. Here, microsecond-long all-atom simulations of the Cterminal portion of the SARS-CoV-2/SARS-CoV Nsp1 in complex with the 40S ribosome disclose that SARS-CoV-2 Nsp1 has evolved from its SARS-CoV ortholog to more effectively hijack the ribosome by undergoing a critical switch of Q/E158 and E/Q159 residues that perfects Nsp1's interactions with the ribosome. Our outcomes offer a basis for understanding the sophisticated mechanisms underlying SARS-CoV-2 diversion and exploitation of human cell components to its deadly purposes.

引用

页码：11745 / 11750

页数：6

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