{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T19:36:09Z","timestamp":1789673769110,"version":"4.0.1"},"reference-count":56,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T00:00:00Z","timestamp":1633651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>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\u2019s 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\u2013brain 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.<\/jats:p>","DOI":"10.3390\/v13102021","type":"journal-article","created":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T01:59:47Z","timestamp":1633917587000},"page":"2021","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Spike Proteins of SARS-CoV-2 Induce Pathological Changes in Molecular Delivery and Metabolic Function in the Brain Endothelial Cells"],"prefix":"10.3390","volume":"13","author":[{"given":"Eun Seon","family":"Kim","sequence":"first","affiliation":[{"name":"Neuroimmunology Laboratory, Dementia Research Group, Korea Brain Research Institute, Sinseo, Daegu 41062, Korea"},{"name":"Department of Brain & Cognitive Sciences, DGIST, Daegu 42988, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Tae","family":"Jeon","sequence":"additional","affiliation":[{"name":"Neuroimmunology Laboratory, Dementia Research Group, Korea Brain Research Institute, Sinseo, Daegu 41062, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyu-Sung","family":"Kim","sequence":"additional","affiliation":[{"name":"Neuroimmunology Laboratory, Dementia Research Group, Korea Brain Research Institute, Sinseo, Daegu 41062, Korea"},{"name":"Department of Brain & Cognitive Sciences, DGIST, Daegu 42988, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suji","family":"Lee","sequence":"additional","affiliation":[{"name":"Neuroimmunology Laboratory, Dementia Research Group, Korea Brain Research Institute, Sinseo, Daegu 41062, Korea"},{"name":"Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King\u2019s College London, 16 De Crespigny Park, London SE5 8AF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suji","family":"Kim","sequence":"additional","affiliation":[{"name":"Neuroimmunology Laboratory, Dementia Research Group, Korea Brain Research Institute, Sinseo, Daegu 41062, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Do-Geun","family":"Kim","sequence":"additional","affiliation":[{"name":"Neuroimmunology Laboratory, Dementia Research Group, Korea Brain Research Institute, Sinseo, Daegu 41062, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.jad.2020.08.001","article-title":"Impact of COVID-19 pandemic on mental health in the general population: A systematic review","volume":"277","author":"Xiong","year":"2020","journal-title":"J. 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