Evidence map›Paper›PMID 36847528›Full record

ArticleJournal of virology2023

All Domains of SARS-CoV-2 nsp1 Determine Translational Shutoff and Cytotoxicity of the Protein.

Ilya Frolov, Tatiana Agback, Oksana Palchevska, Francisco Dominguez, Alexander Lomzov, Peter Agback, Elena I Frolova

Open access · hybridAbstract read
In one paragraph

Article in Journal of virology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
3.5field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 18 citations in OpenAlex.

  1. Enhanced efficacy of a next-generation EEEV self-replicating RNA platform for combination cancer immunotherapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  2. SARS-CoV-2 and MERS-CoV disrupt host protein synthesis via nsp1 with differential effects on the integrated stress response.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
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  13. Host factors of SARS-CoV-2 in infection, pathogenesis, and long-term effects.Frontiers in cellular and infection microbiology · 2024
    Review
  14. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 3 countries.

Ilya FrolovDepartment of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.ORCID 0000-0002-8548-2517
Tatiana AgbackDepartment of Molecular Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Oksana PalchevskaDepartment of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.ORCID 0000-0001-5841-1628
Francisco DominguezDepartment of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Alexander LomzovDepartment of Molecular Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Peter AgbackDepartment of Molecular Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Elena I FrolovaDepartment of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.ORCID 0000-0001-6523-9336
University of Alabama at Birmingham · USSwedish University of Agricultural Sciences · SE

Funding

Mechanistic role of ns2 protein in evasion of innate immune response by alphavirusesR01AI133159 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI FROLOVA, ELENA I · 2017 to 2021
$3.0M
Alphavirus nsP3 protein: roles of intrinsically disordered region in virus replication and pathogenesisR01AI118867 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI FROLOVA, ELENA I · 2015 to 2019
$1.8M
Mechanistic understanding of SH3 domain-containing protein function in alphavirus replicationR21AI146969 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI FROLOV, ILYA V. · 2019 to 2020
$401k
NIAID NIH HHS R01 AI118867NIAID NIH HHS R01 AI133159NIAID NIH HHS R21 AI146969
6 · The paper itself

Abstract

Replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strongly affects cellular metabolism and results in rapid development of the cytopathic effect (CPE). The hallmarks of virus-induced modifications are inhibition of translation of cellular mRNAs and redirection of the cellular translational machinery to the synthesis of virus-specific proteins. The multifunctional nonstructural protein 1 (nsp1) of SARS-CoV-2 is a major virulence factor and a key contributor to the development of translational shutoff. In this study, we applied a wide range of virological and structural approaches to further analyze nsp1 functions. The expression of this protein alone was found to be sufficient to cause CPE. However, we selected several nsp1 mutants exhibiting noncytopathic phenotypes. The attenuating mutations were detected in three clusters, located in the C-terminal helices, in one of the loops of the structured domain and in the junction of the disordered and structured fragment of nsp1. NMR-based analysis of the wild type nsp1 and its mutants did not confirm the existence of a stable β5-strand that was proposed by the X-ray structure. In solution, this protein appears to be present in a dynamic conformation, which is required for its functions in CPE development and viral replication. The NMR data also suggest a dynamic interaction between the N-terminal and C-terminal domains. The identified nsp1 mutations make this protein noncytotoxic and incapable of inducing translational shutoff, but they do not result in deleterious effects on viral cytopathogenicity.

Indexed as

COVID-19SARS-CoV-2HumansViral Nonstructural ProteinsVirus ReplicationViral Nonstructural Proteinsattenuating mutationscoronaviruscytotoxicitynsp1nuclear magnetic resonanceprotein structure-functionSARS-CoV-2translation inhibition

Identifiers

PMID36847528
PMCPMC10062135
OpenAlexW4322493843

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.