Evidence map›Paper›PMID 37511350›Full record

ArticleInternational journal of molecular sciences2023

Insights into the SARS-CoV-2 ORF6 Mechanism of Action.

Elena Krachmarova, Peicho Petkov, Elena Lilkova, Nevena Ilieva, Miroslav Rangelov, Nadezhda Todorova, Kristina Malinova, Rossitsa Hristova, Genoveva Nacheva, Anastas Gospodinov and 1 more

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

6 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Interferon-International journal of molecular sciences · 2024
    Article
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

11 authors at 2 institutions in 1 country.

Elena KrachmarovaInstitute of Molecular Biology "Acad. Roumen Tsanev", Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.ORCID 0000-0002-9501-0724
Peicho PetkovFaculty of Physics, Sofia University "St. Kliment Ohridski", 1164 Sofia, Bulgaria.ORCID 0000-0002-0420-9480
Elena LilkovaInstitute of Information and Communication Technologies, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.ORCID 0000-0003-2008-710X
Nevena IlievaInstitute of Information and Communication Technologies, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.ORCID 0000-0002-2372-2319
Miroslav RangelovInstitute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.ORCID 0000-0002-7953-7593
Nadezhda TodorovaInstitute of Biodiversity and Ecosystem Research, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.ORCID 0000-0002-7195-195X
Kristina MalinovaInstitute of Molecular Biology "Acad. Roumen Tsanev", Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
Rossitsa HristovaInstitute of Molecular Biology "Acad. Roumen Tsanev", Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.ORCID 0000-0001-8362-5396
Genoveva NachevaInstitute of Molecular Biology "Acad. Roumen Tsanev", Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.ORCID 0000-0001-5663-8589
Anastas GospodinovInstitute of Molecular Biology "Acad. Roumen Tsanev", Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.ORCID 0000-0001-6216-9563
Leandar LitovFaculty of Physics, Sofia University "St. Kliment Ohridski", 1164 Sofia, Bulgaria.ORCID 0000-0002-8511-6883
Bulgarian Academy of Sciences · BGSofia University "St. Kliment Ohridski" · BG

Funding

Bulgarian Science Fund KP-06-DK1/5/2021 SARSIMM
6 · The paper itself

Abstract

ORF6 is responsible for suppressing the immune response of cells infected by the SARS-CoV-2 virus. It is also the most toxic protein of SARS-CoV-2, and its actions are associated with the viral pathogenicity. Here, we study in silico and in vitro the structure of the protein, its interaction with RAE1 and the mechanism of action behind its high toxicity. We show both computationally and experimentally that SARS-CoV-2 ORF6, embedded in the cytoplasmic membranes, binds to RAE1 and sequesters it in the cytoplasm, thus depleting its availability in the nucleus and impairing nucleocytoplasmic mRNA transport. This negatively affects the cellular genome stability by compromising the cell cycle progression into the S-phase and by promoting the accumulation of RNA-DNA hybrids. Understanding the multiple ways in which ORF6 affects DNA replication may also have important implications for elucidating the pathogenicity of SARS-CoV-2 and developing therapeutic strategies to mitigate its deleterious effects on host cells.

Indexed as

COVID-19SARS-CoV-2Active Transport, Cell NucleusCytoplasmHumans3D molecular structure modellingcell cyclecyclin EDNA replication stressmolecular dynamics simulationsR-loopsSARS-CoV-2 ORF6–RAE1 binding

Identifiers

PMID37511350
PMCPMC10380535
OpenAlexW4384826917

What Socratic holds

Textmetadata
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 Socratic graph.