ArticleViruses2021
Spike Proteins of SARS-CoV-2 Induce Pathological Changes in Molecular Delivery and Metabolic Function in the Brain Endothelial Cells.
Article in Viruses, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 68 citations in OpenAlex.
- Effects of Exogenous SARS-CoV-2 S1 Protein and mRNA Vaccines on Mixed Neuronal-Glial Cell Cultures.Medicina (Kaunas, Lithuania) · 2026Article
- From HIV to SARS-CoV-2 associated neurological disorder ("HAND" to "SAND"): Viral infection as a "time-bomb" for the aging brain.Neuroscience applied · 2026Review
- Review
- The influence of SARS-CoV-2 spike protein exposure on retinal development in the human retinal organoids.Cell & bioscience · 2025Article
- iPSC-derived human cortical organoids display profound alterations of cellular homeostasis following SARS-CoV-2 infection and Spike protein exposure.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Human Leukocyte Antigen (HLA) at the Root of Persistent Antigens and Long COVID.Journal of immunological sciences · 2025Article
- Angiotensin-converting enzyme 2 modulation of pyroptosis pathway in traumatic brain injury: A potential therapeutic target.Clinical and translational medicine · 2025Article
- Pre-pandemic artificial MERS analog of polyfunctional SARS-CoV-2 S1/S2 furin cleavage site domain is unique among spike proteins of genus Betacoronavirus.BMC genomic data · 2024Article
- The penetration of therapeutics across the blood-brain barrier: Classic case studies and clinical implications.Cell reports. Medicine · 2024Review
- Differential Cytokine Responses of APOE3 and APOE4 Blood-brain Barrier Cell Types to SARS-CoV-2 Spike Proteins.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Article
- Possible Role of Cannabis in the Management of Neuroinflammation in Patients with Post-COVID Condition.International journal of molecular sciences · 2024Review
- Infectious Diseases.Advances in neurobiology · 2024Review
- Mitochondria in COVID-19: from cellular and molecular perspective.Frontiers in physiology · 2024Review
- The mRNA-LNP vaccines - the good, the bad and the ugly?Frontiers in immunology · 2024Review
- Review
- 'Spikeopathy': COVID-19 Spike Protein Is Pathogenic, from Both Virus and Vaccine mRNA.Biomedicines · 2023Review
- SARS-CoV-2 spike protein induces lung endothelial cell dysfunction and thrombo-inflammation depending on the C3a/C3a receptor signalling.Scientific reports · 2023Article
- Vaccination-Associated Myocarditis and Myocardial Injury.Circulation research · 2023Review
- COVID-19 as a trigger of Guillain-Barré syndrome: A review of the molecular mechanism.Immunity, inflammation and disease · 2023Review
- The role of the blood-brain barrier during neurological disease and infection.Biochemical Society transactions · 2023Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease (COVID-19), is currently infecting millions of people worldwide and is causing drastic changes in people's lives. Recent studies have shown that neurological symptoms are a major issue for people infected with SARS-CoV-2. However, the mechanism through which the pathological effects emerge is still unclear. Brain endothelial cells (ECs), one of the components of the blood-brain barrier, are a major hurdle for the entry of pathogenic or infectious agents into the brain. They strongly express angiotensin converting enzyme 2 (ACE2) for its normal physiological function, which is also well-known to be an opportunistic receptor for SARS-CoV-2 spike protein, facilitating their entry into host cells. First, we identified rapid internalization of the receptor-binding domain (RBD) S1 domain (S1) and active trimer (Trimer) of SARS-CoV-2 spike protein through ACE2 in brain ECs. Moreover, internalized S1 increased Rab5, an early endosomal marker while Trimer decreased Rab5 in the brain ECs. Similarly, the permeability of transferrin and dextran was increased in S1 treatment but decreased in Trimer, respectively. Furthermore, S1 and Trimer both induced mitochondrial damage including functional deficits in mitochondrial respiration. Overall, this study shows that SARS-CoV-2 itself has toxic effects on the brain ECs including defective molecular delivery and metabolic function, suggesting a potential pathological mechanism to induce neurological signs in the brain.
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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.