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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

Overview of attention for article published in Stem Cell Research & Therapy, September 2023
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (93rd percentile)
  • High Attention Score compared to outputs of the same age and source (97th percentile)

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2 news outlets
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24 X users

Citations

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4 Dimensions

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7 Mendeley
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Title
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
Published in
Stem Cell Research & Therapy, September 2023
DOI 10.1186/s13287-023-03485-3
Pubmed ID
Authors

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

Abstract

Cardiovascular 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. CMs 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. Nsp6, 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 Ca2+ handling in hPSC-CMs. Importantly, administration of FDA-approved drugs, ivermectin and meclizine, could restore ATP levels, thereby mitigating apoptosis and dysfunction in hPSC-CMs overexpressing Nsp6, Nsp8, or M. Overall, 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.

X Demographics

X Demographics

The data shown below were collected from the profiles of 24 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 7 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 7 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 1 14%
Student > Master 1 14%
Unknown 5 71%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 2 29%
Unknown 5 71%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 31. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 12 April 2024.
All research outputs
#1,301,051
of 25,852,155 outputs
Outputs from Stem Cell Research & Therapy
#61
of 2,812 outputs
Outputs of similar age
#22,430
of 356,312 outputs
Outputs of similar age from Stem Cell Research & Therapy
#2
of 79 outputs
Altmetric has tracked 25,852,155 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 94th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,812 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.3. This one has done particularly well, scoring higher than 97% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 356,312 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 93% of its contemporaries.
We're also able to compare this research output to 79 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 97% of its contemporaries.