ArticleAmerican journal of physiology. Lung cellular and molecular physiology2021
The SARS-CoV-2 spike protein subunit S1 induces COVID-19-like acute lung injury in Κ18-hACE2 transgenic mice and barrier dysfunction in human endothelial cells.
Article in American journal of physiology. Lung cellular and molecular physiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.
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Who cites it
83 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.
- Global research progress of endothelial cells and ALI/ARDS: a bibliometric analysis.Frontiers in physiology · 2024Pooled it
- SARS-CoV-2 spike-armed vesicular stomatitis virus recapitulates severe COVID-19 acute respiratory distress syndrome in mice.iScience · 2026Article
- A Dual-Membrane Biomimetic Nanoplatform Enables Triple-Modal Therapy Against SARS-CoV-2 Through Viral Decoy, Inflammation Neutralizing, and Intracellular RNAi.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- T1R3 Anchors ACE2 at the Pulmonary Endothelial Cell Surface to Attenuate Vascular Injury Following SARS-CoV-2 Spike 1 Protein Exposure In Vitro.Journal of cellular and molecular medicine · 2026Article
- Spike 1 protein of SARS-CoV-2 induces endothelial inflammation and vascular dysfunction through interferon ISG15-dependent mechanisms.Cardiovascular research · 2026Article
- Lung Dysfunction and Systemic Inflammation: A Role for HO-1 and NLRP3 in a COVID-19 Murine Model.Research square · 2026Article
- Article
- Cellular and Molecular Mechanisms of SARS-CoV-2 Spike Protein-Induced Endothelial Dysfunction.Cells · 2026Review
- Recombinant SARS-Cov-2 spike protein S1 subunit upregulates P2 × 7-NLRP3 leading to macrophage pyroptosis promoting acute lung injury.Respiratory research · 2026Article
- Targeting PTP4A3 with KVX-053 mitigates alcohol-amplified SARS-CoV-2 spike protein-induced acute lung injury.Frontiers in pharmacology · 2026Article
- The PTP4A3 inhibitor KVX-053 reduces Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virulence, inflammation, and development of acute lung injury in K18-hACE2 mice.Respiratory research · 2025Article
- Sustained Vascular Inflammatory Effects of SARS-CoV-2 Spike Protein on Human Endothelial Cells.Inflammation · 2025Article
- SARS-CoV-2 spike treatment and transfection impairs airway epithelial repair.ERJ open research · 2025Article
- Review
- Endothelial growth media components alter SARS-CoV-2 spike-directed growth kinetics.Journal of virological methods · 2025Article
- Vascular Pathogenesis in Acute and Long COVID: Current Insights and Therapeutic Outlook.Seminars in thrombosis and hemostasis · 2025Review
- Acute lung injury induced by recombinant SARS-CoV-2 spike protein subunit S1 in mice.Respiratory research · 2025Article
- The endothelial-immunothrombotic storm in viral sepsis: lessons from COVID-19.Frontiers in immunology · 2025Review
- Article
- Multifaceted role of SARS-CoV-2 structural proteins in lung injury.Frontiers in immunology · 2024Review
23 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Acute lung injury (ALI) leading to acute respiratory distress syndrome is the major cause of COVID-19 lethality. Cell entry of SARS-CoV-2 occurs via the interaction between its surface spike protein (SP) and angiotensin-converting enzyme-2 (ACE2). It is unknown if the viral spike protein alone is capable of altering lung vascular permeability in the lungs or producing lung injury in vivo. To that end, we intratracheally instilled the S1 subunit of SARS-CoV-2 spike protein (S1SP) in K18-hACE2 transgenic mice that overexpress human ACE2 and examined signs of COVID-19-associated lung injury 72 h later. Controls included K18-hACE2 mice that received saline or the intact SP and wild-type (WT) mice that received S1SP. K18-hACE2 mice instilled with S1SP exhibited a decline in body weight, dramatically increased white blood cells and protein concentrations in bronchoalveolar lavage fluid (BALF), upregulation of multiple inflammatory cytokines in BALF and serum, histological evidence of lung injury, and activation of signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways in the lung. K18-hACE2 mice that received either saline or SP exhibited little or no evidence of lung injury. WT mice that received S1SP exhibited a milder form of COVID-19 symptoms, compared with the K18-hACE2 mice. Furthermore, S1SP, but not SP, decreased cultured human pulmonary microvascular transendothelial resistance (TER) and barrier function. This is the first demonstration of a COVID-19-like response by an essential virus-encoded protein by SARS-CoV-2 in vivo. This model of COVID-19-induced ALI may assist in the investigation of new therapeutic approaches for the management of COVID-19 and other coronaviruses.
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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.