Molecular Basis of SARS-CoV-2 Nsp1-Induced Immune Translational Shutdown as Revealed by All-Atom Simulations.
J Phys Chem Lett
; 12(48): 11745-11750, 2021 Dec 09.
Article
in English
| MEDLINE | ID: covidwho-1545576
ABSTRACT
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 C-terminal 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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Viral Nonstructural Proteins
/
Ribosome Subunits, Small, Eukaryotic
/
Molecular Dynamics Simulation
/
SARS-CoV-2
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal:
J Phys Chem Lett
Year:
2021
Document Type:
Article
Affiliation country:
Acs.jpclett.1c03441
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