Evidence map›Paper›PMID 34858397›Full record

ArticleFrontiers in immunology2021

Metformin Suppresses Monocyte Immunometabolic Activation by SARS-CoV-2 Spike Protein Subunit 1.

Theodore J Cory, Russell S Emmons, Johnathan R Yarbro, Kierstin L Davis, Brandt D Pence

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 3 pooled it
1.8field-weighted citation impact, top 12% 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

27 citing papers in PubMed, 3 syntheses or guidelines pooled it, 32 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Article
  5. Review
  6. Article
  7. Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Review
  15. Article
  16. Review
  17. Review
  18. Review
  19. Review
  20. Abnormal glucose metabolism in virus associated sepsis.Frontiers in cellular and infection microbiology · 2023
    Review
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

5 authors at 2 institutions in 1 country.

Theodore J CoryDepartment of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, United States.
Russell S EmmonsCollege of Health Sciences, University of Memphis, Memphis, TN, United States.
Johnathan R YarbroCollege of Health Sciences, University of Memphis, Memphis, TN, United States.
Kierstin L DavisCollege of Health Sciences, University of Memphis, Memphis, TN, United States.
Brandt D PenceCollege of Health Sciences, University of Memphis, Memphis, TN, United States.
University of Memphis · USUniversity of Tennessee Health Science Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

A hallmark of COVID-19 is a hyperinflammatory state associated with severity. Monocytes undergo metabolic reprogramming and produce inflammatory cytokines when stimulated with SARS-CoV-2. We hypothesized that binding by the viral spike protein mediates this effect, and that drugs which regulate immunometabolism could inhibit the inflammatory response. Monocytes stimulated with recombinant SARS-CoV-2 spike protein subunit 1 showed a dose-dependent increase in glycolytic metabolism associated with production of pro-inflammatory cytokines. This response was dependent on hypoxia-inducible factor-1α, as chetomin inhibited glycolysis and cytokine production. Inhibition of glycolytic metabolism by 2-deoxyglucose (2-DG) or glucose deprivation also inhibited the glycolytic response, and 2-DG strongly suppressed cytokine production. Glucose-deprived monocytes rescued cytokine production by upregulating oxidative phosphorylation, an effect which was not present in 2-DG-treated monocytes due to the known effect of 2-DG on suppressing mitochondrial metabolism. Finally, pre-treatment of monocytes with metformin strongly suppressed spike protein-mediated cytokine production and metabolic reprogramming. Likewise, metformin pre-treatment blocked cytokine induction by SARS-CoV-2 strain WA1/2020 in direct infection experiments. In summary, the SARS-CoV-2 spike protein induces a pro-inflammatory immunometabolic response in monocytes that can be suppressed by metformin, and metformin likewise suppresses inflammatory responses to live SARS-CoV-2. This has potential implications for the treatment of hyperinflammation during COVID-19.

Indexed as

Cells, CulturedCOVID-19HumansMetforminMonocytesSARS-CoV-2Spike Glycoprotein, CoronavirusMetforminSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2COVID-19immunometabolisminflammationmonocyteSARS-CoV-2

Identifiers

PMID34858397
PMCPMC8631967
OpenAlexW3211675872

What OpenQuestion 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 OpenQuestion graph.