ArticleMolecular biology of the cell2022
SARS-CoV-2 down-regulates ACE2 through lysosomal degradation.
Article in Molecular biology of the cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Therapeutic effects of vitamin D supplementation on COVID-19 aggravation: a systematic review and meta-analysis of randomized controlled trials.Frontiers in pharmacology · 2024Pooled it
- PM2.5 toxin benzo[a]pyrene induces life-limiting inflammation and oxidative stress in the airway by up-regulation of TRPC6 and inactivation of β2AR/CFTR signaling.bioRxiv : the preprint server for biology · 2026Article
- The Renin Angiotensin System: Insights into the Role of ACE2 in Glomerular Injury Including SARS-CoV-2 Infection.International journal of molecular sciences · 2026Review
- RAAS antagonists dampen the SARS-CoV-2 infection in ex-vivo cultured human precision-cut lung slices.Respiratory research · 2026Article
- Roles of Reactive Oxygen Species in Relationships Between Viral Infections and Alzheimer's Disease and Related Dementia.Antioxidants (Basel, Switzerland) · 2026Review
- Expression of angiotensin-converting enzyme 2, transmembrane serine protease 2, and sirtuin 1 proteins in lungs of different age groups.Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia · 2026Article
- Thymidine phosphorylase promotes SARS-CoV-2 spike protein-driven lung tumor development.Frontiers in immunology · 2026Article
- Autophagy in emerging and highly concerned severe zoonotic infectious diseases.Frontiers in immunology · 2026Review
- Expression ofBiomedical reports · 2025Article
- ACE2: Friend or Foe in Post-COVID-19 Neurodegeneration?International journal of molecular sciences · 2025Review
- Gut infection and dysbiosis are hallmarks of severe SARS-CoV-2 variants.Npj viruses · 2025Article
- Revisiting the monocrotaline-treated rat as a model of inflammatory lung disease: COVID-19 and future pandemic threats?Animal models and experimental medicine · 2025Review
- Angiotensin-Converting Enzyme-2 (ACE2) Downregulation During Coronavirus Infection.Molecular biotechnology · 2025Review
- SARS-Cov-2 Replication in a Blood-Brain Barrier Model Established with Human Brain Microvascular Endothelial Cells Induces Permeability and Disables ACE2-Dependent Regulation of Bradykinin B1 Receptor.International journal of molecular sciences · 2025Article
- Article
- ACE2 and TMPRSS2 gene expression is reduced acutely in SARS-CoV-2 patients but returns to normal with recovery.Scientific reports · 2025Article
- Modulation of RAAS receptors and miRNAs in COVID-19: implications for disease severity, immune response, and potential therapeutic targets.BMC infectious diseases · 2025Observational
- Inhibition of kinin B1 receptor alleviates SARS-CoV-2-induced long-lasting cardiovascular complications.American journal of physiology. Heart and circulatory physiology · 2025Article
- The prognostic role of cardiac and inflammatory biomarkers in extubation failure in patients with COVID-19 acute respiratory distress syndrome.Annals of intensive care · 2025Article
- Microbiome dysbiosis in SARS-CoV-2 infection: implication for pathophysiology and management strategies of COVID-19.Frontiers in cellular and infection microbiology · 2025Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes its Spike (S) glycoprotein to bind to the angiotensin-converting enzyme 2 (ACE2) receptor for cellular entry. ACE2 is a critical negative regulator of the renin-angiotensin system and plays a protective role in preventing tissue injury. Expression of ACE2 has been shown to decrease upon infection by SARS-CoV. However, whether SARS-CoV-2 down-regulates ACE2 and the underlying mechanism and biological impact of this down-regulation have not been well defined. Here we show that the SARS-CoV-2 infection down-regulates ACE2 in vivo in an animal model, and in cultured cells in vitro, by inducing clathrin- and AP2-dependent endocytosis, leading to its degradation in the lysosome. SARS-CoV-2 S-treated cells and ACE2 knockdown cells exhibit similar alterations in downstream gene expression, with a pattern indicative of activated cytokine signaling that is associated with respiratory distress and inflammatory diseases often observed in COVID-19 patients. Finally, we have identified a soluble ACE2 fragment with a stronger binding to SARS-CoV-2 S that can efficiently block ACE2 down-regulation and viral infection. Thus, our study suggests that ACE2 down-regulation represents an important mechanism underlying SARS-CoV-2-associated pathology, and blocking this process could be a promising therapeutic strategy.
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