ArticleBiochimica et biophysica acta. Molecular basis of disease2021
SARS-CoV-2 spike promotes inflammation and apoptosis through autophagy by ROS-suppressed PI3K/AKT/mTOR signaling.
Article in Biochimica et biophysica acta. Molecular basis of disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
125 citing papers in PubMed, 1 synthesis or guideline pooled it, 203 citations in OpenAlex.
- Smoking and vaping alter genes related to mechanisms of SARS-CoV-2 susceptibility and severity: a systematic review and meta-analysis.The European respiratory journal · 2024Pooled it
- Trial
- Article
- Virus-Induced Intestinal Barrier Injury: Mechanisms and Therapeutic Perspectives.Veterinary sciences · 2026Review
- Cardiac-derived extracellular vesicles carrying miR-4433b-3p accelerate cognitive decline and brain aging by suppressing TP53INP2-mediated neuronal autophagy in mice.Communications biology · 2026Article
- Therapeutic effect of N-acetylcysteine in severe or critical coronavirus disease 2019 pneumonia: A retrospective cohort study.The Journal of international medical research · 2026Article
- Antiviral effects of Codonopsis pilosula extract and its bioactive components against porcine epidemic diarrhea virus in vitro via the AMPK/mTOR pathway.BMC veterinary research · 2026Article
- SARS-CoV-2 Spike Protein S2 Subunit: Recombinant Protein Expression Analysis, Purification, and Its Regulatory Effect on IGF-1R Expression.The protein journal · 2026Article
- Senecavirus a VP2 protein orchestrates PRDX1 degradation through dual autophagy pathways: macroautophagy and chaperone-mediated autophagy.Autophagy · 2026Article
- The cGAS-STING pathway at the crossroads of neuroimmunology: bridging innate immunity to aging and neurodegeneration.Biomarker research · 2026Review
- Cellular and Molecular Mechanisms of SARS-CoV-2 Spike Protein-Induced Endothelial Dysfunction.Cells · 2026Review
- Tetrandrine-driven autophagy suppresses SARS-CoV-2 replication by modulating cholesterol and IGF signaling pathways.Cell death discovery · 2026Article
- Roles of Reactive Oxygen Species in Relationships Between Viral Infections and Alzheimer's Disease and Related Dementia.Antioxidants (Basel, Switzerland) · 2026Review
- JinHuangJieDu (JHJD) formula attenuates SARS-CoV-2 infection by interrupting RBD-ACE2 binding and HIF-1α-dependent inflammation.Frontiers in medicine · 2026Article
- Comparative progress on the mechanisms of airway mucosal injury induced by different pathogens: SARS-CoV-2, influenza A virus, and Mycoplasma pneumoniae.Frontiers in cellular and infection microbiology · 2026Review
- Mammalian innate antiviral defenses: beyond interferon.Journal of virology · 2025Review
- The role of Na,K‑ATPase in lung diseases (Review).Molecular medicine reports · 2025Review
- Role of Ferroptosis on Lung Epithelial Cells in Disease Progression and Treatment: A Review.Medical science monitor : international medical journal of experimental and clinical research · 2025Review
- STAT5-c-Myc-axis regulates B cell metabolism in vaccinated individuals and COVID-19 recovered patients.Virologica Sinica · 2025Article
- Hydroxychloroquine improves manifestation of PE rats under oxidative stress by regulating the PI3K/AKT/mTOR signaling pathway to inhibit autophagy.Scientific reports · 2025Article
65 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection-induced inflammatory responses are largely responsible for the death of novel coronavirus disease 2019 (COVID-19) patients. However, the mechanism by which SARS-CoV-2 triggers inflammatory responses remains unclear. Here, we aimed to explore the regulatory role of SARS-CoV-2 spike protein in infected cells and attempted to elucidate the molecular mechanism of SARS-CoV-2-induced inflammation.
methodsSARS-CoV-2 spike pseudovirions (SCV-2-S) were generated using the spike-expressing virus packaging system. Western blot, mCherry-GFP-LC3 labeling, immunofluorescence, and RNA-seq were performed to examine the regulatory mechanism of SCV-2-S in autophagic response. The effects of SCV-2-S on apoptosis were evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), Western blot, and flow cytometry analysis. Enzyme-linked immunosorbent assay (ELISA) was carried out to examine the mechanism of SCV-2-S in inflammatory responses.
resultsAngiotensin-converting enzyme 2 (ACE2)-mediated SCV-2-S infection induced autophagy and apoptosis in human bronchial epithelial and microvascular endothelial cells. Mechanistically, SCV-2-S inhibited the PI3K/AKT/mTOR pathway by upregulating intracellular reactive oxygen species (ROS) levels, thus promoting the autophagic response. Ultimately, SCV-2-S-induced autophagy triggered inflammatory responses and apoptosis in infected cells. These findings not only improve our understanding of the mechanism underlying SARS-CoV-2 infection-induced pathogenic inflammation but also have important implications for developing anti-inflammatory therapies, such as ROS and autophagy inhibitors, for COVID-19 patients.
Indexed as
Identifiers
What OpenQuestion holds
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.