ArticleCommunications biology2022
The spike of SARS-CoV-2 promotes metabolic rewiring in hepatocytes.
Article in Communications biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Metformin for Treatment of Acute COVID-19: Systematic Review of Clinical Trial Data Against SARS-CoV-2.Diabetes care · 2023Pooled it
- PPARγ mediated enhanced lipid biogenesis fuelseLife · 2025Article
- Mitochondrial Reactive Oxygen Species: A Unifying Mechanism in Long COVID and Spike Protein-Associated Injury: A Narrative Review.Biomolecules · 2025Review
- Integrated multi‑omics analysis of liver metabolic dysregulation in ACE2 knockout mice.International journal of molecular medicine · 2025Article
- Post-COVID Metabolic Fallout: A Growing Threat of New-Onset and Exacerbated Diabetes.Biomedicines · 2025Review
- Post-COVID-19 Pandemic Sequelae in Liver Diseases.Life (Basel, Switzerland) · 2025Review
- Gut microbiota in gastrointestinal diseases: Insights and therapeutic strategies.World journal of gastroenterology · 2024Article
- Hepatic angiotensin-converting enzyme 2 expression in metabolic dysfunction-associated steatotic liver disease and in patients with fatal COVID-19.World journal of gastroenterology · 2024Article
- Human-induced pluripotent stem cell-derived hepatocyte platform in modeling of SARS-CoV-2 infection.JGH open : an open access journal of gastroenterology and hepatology · 2024Article
- COVID-19-Induced Diabetes Mellitus: Comprehensive Cellular and Molecular Mechanistic Insights.Pathophysiology : the official journal of the International Society for Pathophysiology · 2024Review
- Asialoglycoprotein receptor 1 promotes SARS-CoV-2 infection of human normal hepatocytes.Signal transduction and targeted therapy · 2024Article
- Molecular mechanisms underlying SARS-CoV-2 hepatotropism and liver damage.World journal of hepatology · 2024Article
- Unraveling metabolic signatures in SARS-CoV-2 variant infections using multiomics analysis.Frontiers in immunology · 2024Article
- SARS-CoV-2 receptor ACE2 is upregulated by fatty acids in human MASH.JHEP reports : innovation in hepatology · 2024Article
- COVID-19 associated liver injury: An updated review on the mechanisms and management of risk groups.Liver research (Beijing, China) · 2023Review
- Article
- Unveiling the potential pleiotropic effects of metformin in treating COVID-19: a comprehensive review.Frontiers in molecular biosciences · 2023Review
- Application of the humanized mouse model in research into SARS-CoV-2 infection (Review).Medicine internationalReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
26 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a multi-organ damage that includes hepatic dysfunction, which has been observed in over 50% of COVID-19 patients. Liver injury in COVID-19 could be attributed to the cytopathic effects, exacerbated immune responses or treatment-associated drug toxicity. Herein we demonstrate that hepatocytes are susceptible to infection in different models: primary hepatocytes derived from humanized angiotensin-converting enzyme-2 mice (hACE2) and primary human hepatocytes. Pseudotyped viral particles expressing the full-length spike of SARS-CoV-2 and recombinant receptor binding domain (RBD) bind to ACE2 expressed by hepatocytes, promoting metabolic reprogramming towards glycolysis but also impaired mitochondrial activity. Human and hACE2 primary hepatocytes, where steatosis and inflammation were induced by methionine and choline deprivation, are more vulnerable to infection. Inhibition of the renin-angiotensin system increases the susceptibility of primary hepatocytes to infection with pseudotyped viral particles. Metformin, a common therapeutic option for hyperglycemia in type 2 diabetes patients known to partially attenuate fatty liver, reduces the infection of human and hACE2 hepatocytes. In summary, we provide evidence that hepatocytes are amenable to infection with SARS-CoV-2 pseudovirus, and we propose that metformin could be a therapeutic option to attenuate infection by SARS-CoV-2 in patients with fatty liver.
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Registered trials
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.