Clinically observed deletions in SARS-CoV-2 Nsp1 affect its stability and ability to inhibit translation

Pravin Kumar, Erin Schexnaydre, Karim Rafie, Tatsuaki Kurata, Ilya Terenin, Vasili Hauryliuk, Lars-Anders Carlson

Research output: Contribution to journalArticlepeer-review

Abstract

Nonstructural protein 1 (Nsp1) of SARS-CoV-2 inhibits host cell translation through an interaction between its C-terminal domain and the 40S ribosome. The N-terminal domain (NTD) of Nsp1 is a target of recurring deletions, some of which are associated with altered COVID-19 disease progression. Here, we characterize the efficiency of translational inhibition by clinically observed Nsp1 deletion variants. We show that a frequent deletion of residues 79-89 severely reduces the ability of Nsp1 to inhibit translation while not abrogating Nsp1 binding to the 40S. Notably, while the SARS-CoV-2 5' untranslated region enhances translation of mRNA, it does not protect from Nsp1-mediated inhibition. Finally, thermal stability measurements and structure predictions reveal a correlation between stability of the NTD and the efficiency of translation inhibition.

Original languageEnglish
Pages (from-to)1203-1213
JournalFEBS Letters
Volume596
Issue number9
Early online date2022 Apr 17
DOIs
Publication statusPublished - 2022

Bibliographical note

This article is protected by copyright. All rights reserved.

Subject classification (UKÄ)

  • Infectious Medicine

Free keywords

  • Nsp1
  • SARS-CoV-2
  • COVID-19
  • pathogenicity
  • ribosome
  • translation
  • virus

Fingerprint

Dive into the research topics of 'Clinically observed deletions in SARS-CoV-2 Nsp1 affect its stability and ability to inhibit translation'. Together they form a unique fingerprint.

Cite this