Evidence map›Paper›PMID 37705046›Full record

ArticleStem cell research & therapy2023

SARS-CoV-2 viral genes Nsp6, Nsp8, and M compromise cellular ATP levels to impair survival and function of human pluripotent stem cell-derived cardiomyocytes.

Juli Liu, Shiyong Wu, Yucheng Zhang, Cheng Wang, Sheng Liu, Jun Wan, Lei Yang

Open access · goldAbstract read
In one paragraph

Article in Stem cell research & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

5 citing papers in PubMed, 12 citations in OpenAlex.

  1. Dynamic metabolic modelling of ATP allocation during viral infection.Journal of the Royal Society, Interface · 2026
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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 2 countries.

Juli Liu *Department of Pediatrics, Indiana University School of Medicine, Herman B Wells Center for Pediatric Research, Indianapolis, IN, 46202, USA. juliliu@outlook.com.
Shiyong Wu *Department of Pediatrics, Indiana University School of Medicine, Herman B Wells Center for Pediatric Research, Indianapolis, IN, 46202, USA.
Yucheng ZhangDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Cheng WangDepartment of Pediatrics, Indiana University School of Medicine, Herman B Wells Center for Pediatric Research, Indianapolis, IN, 46202, USA.
Sheng LiuDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Jun WanDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Lei YangDepartment of Pediatrics, Indiana University School of Medicine, Herman B Wells Center for Pediatric Research, Indianapolis, IN, 46202, USA. lyang7@iu.edu.ORCID http://orcid.org/0000-0002-1479-2374
Indiana University School of MedicineGuangdong Academy of Medical Sciences · CN

Funding

Quality Assurance and Quality Control Project Management: Improving Submissions and Study Conduct in the Human Subjects Research Prior Approval ProcessUL1TR002529 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI MOE, SHARON M, WIEHE, SARAH ELIZABETH · 2018 to 2022
$27.2M
NCATS NIH HHS UL1 TR002529
6 · The paper itself

Abstract

backgroundCardiovascular complications significantly augment the overall COVID-19 mortality, largely due to the susceptibility of human cardiomyocytes (CMs) to SARS-CoV-2 virus. SARS-CoV-2 virus encodes 27 genes, whose specific impacts on CM health are not fully understood. This study elucidates the deleterious effects of SARS-CoV-2 genes Nsp6, M, and Nsp8 on human CMs.

methodsCMs were derived from human pluripotent stem cells (hPSCs), including human embryonic stem cells and induced pluripotent stem cells, using 2D and 3D differentiation methods. We overexpressed Nsp6, M, or Nsp8 in hPSCs and then applied whole mRNA-seq and mass spectrometry for multi-omics analysis. Co-immunoprecipitation mass spectrometry was utilized to map the protein interaction networks of Nsp6, M, and Nsp8 within host hiPSC-CMs.

resultsNsp6, Nsp8, and M globally perturb the transcriptome and proteome of hPSC-CMs. SARS-CoV-2 infection and the overexpression of Nsp6, Nsp8, or M coherently upregulated genes associated with apoptosis and immune/inflammation pathways, whereas downregulated genes linked to heart contraction and functions. Global interactome analysis revealed interactions between Nsp6, Nsp8, and M with ATPase subunits. Overexpression of Nsp6, Nsp8, or M significantly reduced cellular ATP levels, markedly increased apoptosis, and compromised Ca

conclusionOverall, our findings uncover the extensive damaging effects of Nsp6, Nsp8, and M on hPSC-CMs, underlining the crucial role of ATP homeostasis in CM death and functional abnormalities induced by these SARS-CoV-2 genes, and reveal the potential therapeutic strategies to alleviate these detrimental effects with FDA-approved drugs.

Indexed as

COVID-19Pluripotent Stem CellsAdenosine TriphosphateGenes, ViralHumansMyocytes, CardiacSARS-CoV-2Adenosine TriphosphateApoptosisCardiac dysfunctionCardiomyocyteCOVID-19Human pluripotent stem cellsSARS-CoV-2

Identifiers

PMID37705046
PMCPMC10500938
OpenAlexW4386723410

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.