ArticleJournal of virology2021
Direct Activation of Endothelial Cells by SARS-CoV-2 Nucleocapsid Protein Is Blocked by Simvastatin.
Article in Journal of virology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05576714 (Investigation of Prognostic Biomarkers, Host Factors and Viral Factors for COVID-19 Associated Encephalopathy/Encephalitis and Multi-systemic Inflammatory Syndrome in Children), which is not on this map. Cited by 61 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.
Investigation of Prognostic Biomarkers, Host Factors and Viral Factors for COVID-19 Associated Encephalopathy/Encephalitis and Multi-systemic Inflammatory Syndrome in Children
Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- Mucosal immune response in biology, disease prevention and treatment.Signal transduction and targeted therapy · 2025Pooled it
- Randomized phase II clinical trial of ruxolitinib plus simvastatin in COVID19 clinical outcome and cytokine evolution.Frontiers in immunology · 2023Trial
- Cellular and Molecular Mechanisms of SARS-CoV-2 Spike Protein-Induced Endothelial Dysfunction.Cells · 2026Review
- SARS-CoV-2 pseudoparticles preferentially infect ectoderm in human embryonic tissues.Frontiers in cell and developmental biology · 2026Article
- A non-spike nucleocapsid R204P mutation in SARS-CoV-2 Omicron XEC enhances inflammation and pathogenicity.Nature communications · 2025Article
- Decoding long COVID-associated cardiovascular dysfunction: Mechanisms, models, and new approach methodologies.Journal of molecular and cellular cardiology · 2025Review
- GlycoRNA-L and glycoRNA-S mediate human monocyte adhesion via binding to Siglec-5.Biochimica et biophysica acta. Molecular cell research · 2025Article
- Review
- SARS-CoV-2 specific adaptations in N protein inhibit NF-κB activation and alter pathogenesis.The Journal of cell biology · 2025Article
- Cardiovascular damage and comorbidities related to long COVID: pathomechanisms, prevention, and therapy.Frontiers in cardiovascular medicine · 2025Review
- Challenging the notion of endothelial infection by SARS-CoV-2: insights from the current scientific evidence.Frontiers in immunology · 2025Article
- Intrinsic factors behind long COVID: exploring the role of nucleocapsid protein in thrombosis.PeerJ · 2025Review
- Cyclophilin-CD147 interaction enables SARS-CoV-2 infection of human monocytes and their activation via Toll-like receptors 7 and 8.Frontiers in immunology · 2025Article
- Assessing the endothelium's role in COVID-19 severity using the HUVEC model.Frontiers in immunology · 2025Article
- TLR2 Activation as a Marker of Severe COVID-19 and a Potential Therapeutic Target.Current medicinal chemistry · 2025Review
- COVID-19 Exacerbates Neurovascular Uncoupling and Contributes to Endothelial Dysfunction in Patients with Mild Cognitive Impairment.Biomolecules · 2024Article
- Article
- Immunity and Coagulation in COVID-19.International journal of molecular sciences · 2024Review
- Long Neuro-COVID-19: Current Mechanistic Views and Therapeutic Perspectives.Biomolecules · 2024Review
- COVID-19-Associated Sepsis: Potential Role of Phytochemicals as Functional Foods and Nutraceuticals.International journal of molecular sciences · 2024Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
- Update of
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Emerging evidence suggests that endothelial activation plays a central role in the pathogenesis of acute respiratory distress syndrome (ARDS) and multiorgan failure in patients with coronavirus disease 2019 (COVID-19). However, the molecular mechanisms underlying endothelial activation in COVID-19 patients remain unclear. In this study, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins that potently activate human endothelial cells were screened to elucidate the molecular mechanisms involved in endothelial activation. It was found that nucleocapsid protein (NP) of SARS-CoV-2 significantly activated human endothelial cells through Toll-like receptor 2 (TLR2)/NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways. Moreover, by screening a natural microbial compound library containing 154 natural compounds, simvastatin was identified as a potent inhibitor of NP-induced endothelial activation. Remarkably, though the protein sequences of N proteins from coronaviruses are highly conserved, only NP from SARS-CoV-2 induced endothelial activation. The NPs from other coronaviruses such as SARS-CoV, Middle East respiratory syndrome coronavirus (MERS-CoV), HUB1-CoV, and influenza virus H1N1 did not activate endothelial cells. These findings are consistent with the results from clinical investigations showing broad endotheliitis and organ injury in severe COVID-19 patients. In conclusion, the study provides insights on SARS-CoV-2-induced vasculopathy and coagulopathy and suggests that simvastatin, an FDA-approved lipid-lowering drug, may help prevent the pathogenesis and improve the outcome of COVID-19 patients.
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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.