Highly mutable influenza is successfully countered based on individual susceptibility and similar precision-like medicine approach should be effective against SARS-COV-2. Among predictive markers to bring precision medicine to COVID-19, circulating ACE2 has potential features being upregulated in both severe COVID-19 and predisposing comorbidities. Spike SARS-CoVs were shown to induce ADAM17-mediated shedding of enzymatic active ACE2, thus accounting for its increased activity that has also been suggested to induce positive feedback loops leading to COVID-19-like manifestations. For this reason, pre-existing ACE2 activity and inhibition of ACE2/ADAM17 zinc-metalloproteases through zinc chelating agents have been proposed to predict COVID-19 outcome before infection and to protect from COVID-19, respectively. Since most diagnostic laboratories are not equipped for enzymatic activity determination, other potential predictive markers of disease progression exploitable by diagnostic laboratories were explored. Concentrations of circulating albumin, zinc, ACE2 protein and its activity were investigated in healthy, diabetic (COVID-19-susceptible) and SARS-CoV-2-negative COVID-19 individuals. ACE2 both protein levels and activity significantly increased in COVID-19 and diabetic patients. Abnormal high levels of ACE2 characterised a subgroup (16-19%) of diabetics, while COVID-19 patients were characterised by significantly higher zinc/albumin ratios, pointing to a relative increase of albumin-unbound zinc species, such as free zinc ones. Data on circulating ACE2 levels are in line with the hypothesis that they can drive susceptibility to COVID-19 and elevated zinc/albumin ratios support the therapeutic use of zinc chelating inhibitors of ACE2/ADAM17 zinc-metalloproteases in a targeted therapy for COVID-19.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10202900 | PMC |
| http://dx.doi.org/10.1016/j.jbior.2023.100973 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Intranasally administrated fusion-inhibitory lipopeptides block SARS-CoV-2 infection in mice and enable long-term protective immunity.
Commun Biol
January 2025
CIRI, Centre International de Recherche en Infectiologie, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Lyon, France.
We have assessed antiviral activity and induction of protective immunity of fusion-inhibitory lipopeptides derived from the C-terminal heptad-repeat domain of SARS-CoV-2 spike glycoprotein in transgenic mice expressing human ACE2 (K18-hACE2). The lipopeptides block SARS-CoV-2 infection in cell lines and lung-derived organotypic cultures. Intranasal administration in mice allows the maintenance of homeostatic transcriptomic immune profile in lungs, prevents body-weight loss, decreases viral load and shedding, and protects mice from death caused by SARS-CoV-2 variants.
View Article and Find Full Text PDFMonocytic reactive oxygen species-induced T cell apoptosis impairs cellular immune response to SARS-CoV-2 mRNA vaccine.
J Allergy Clin Immunol
January 2025
Institute of Human Genetics, UMR9002, CNRS and Montpellier University; Montpellier, France; Montpellier University; Montpellier, France; Immunology Department, University Hospital; Nîmes, France. Electronic address:
Background: We have recently shown that, during acute severe COVID-19, SARS-CoV-2 spike protein (S) induces a cascade of events resulting in T cell apoptosis. Indeed, by neutralizing the protease activity of its receptor, ACE2, S induces an increase in circulating Angiotensin II (AngII), resulting in monocytic release of reactive oxygen species (ROS) and programmed T cell death.
Objective: Here, we tested whether SARS-CoV-2 mRNA vaccines, known to cause the circulation of the vaccine antigen, S-protein receptor binding domain (RBD), might trigger the same cascade.
Characterization and Fluctuations of an Ivermectin Binding Site at the Lipid Raft Interface of the N-Terminal Domain (NTD) of the Spike Protein of SARS-CoV-2 Variants.
Viruses
November 2024
Department of Biology, Faculty of Medicine, Aix-Marseille University, INSERM UA16, 13015 Marseille, France.
Most studies on the docking of ivermectin on the spike protein of SARS-CoV-2 concern the receptor binding domain (RBD) and, more precisely, the RBD interface recognized by the ACE2 receptor. The N-terminal domain (NTD), which controls the initial attachment of the virus to lipid raft gangliosides, has not received the attention it deserves. In this study, we combined molecular modeling and physicochemical approaches to analyze the mode of interaction of ivermectin with the interface of the NTD-facing lipid rafts of the host cell membrane.
View Article and Find Full Text PDFGeneration of a SARS-CoV-2-susceptible mouse model using adenovirus vector expressing human angiotensin-converting enzyme 2 driven by an elongation factor 1α promoter with leftward orientation.
Front Immunol
December 2024
Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Introduction: To analyze the molecular pathogenesis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a small animal model such as mice is needed: human angiotensin converting enzyme 2 (hACE2), the receptor of SARS-CoV-2, needs to be expressed in the respiratory tract of mice.
Methods: We conferred SARS-CoV-2 susceptibility in mice by using an adenoviral vector expressing hACE2 driven by an elongation factor 1α (EF1α) promoter with a leftward orientation.
Results: In this model, severe pneumonia like human COVID-19 was observed in SARS-CoV-2-infected mice, which was confirmed by dramatic infiltration of inflammatory cells in the lung with efficient viral replication.
Fasting recovers age-related hypertension in the rats: reset of renal renin-angiotensin system components and klotho.
BMC Nephrol
December 2024
Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Article Synopsis
- The study examined how intermittent fasting impacts age-related high blood pressure and the renal renin-angiotensin system in rats.
- Older rats showed higher blood pressure and hormone levels associated with hypertension compared to younger rats, as well as lower levels of α-klotho and kidney receptor proteins.
- Intermittent fasting, especially every other day fasting, effectively lowered blood pressure and improved certain RAS components in older rats, indicating its potential benefits for managing age-related hypertension.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!