ArticleNature neuroscience2021
The S1 protein of SARS-CoV-2 crosses the blood-brain barrier in mice.
Article in Nature neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 261 papers, 1 of them a synthesis that pooled it.
What it found
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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
261 citing papers in PubMed, 1 synthesis or guideline pooled it, 436 citations in OpenAlex.
- A systematic review and meta-analysis, investigating dose and time of fluvoxamine treatment efficacy for COVID-19 clinical deterioration, death, and Long-COVID complications.Scientific reports · 2024Pooled it
- Voluntary wheel running behavior is reduced by SARS-CoV-2 S1 administration and mitigates hypothalamic neuroinflammatory processes.Brain, behavior, & immunity - health · 2026Article
- Let-7a-5p/SHIP-1 Axis Drives SARS-CoV-2 Spike-1-Induced Microglial Pyroptosis.International journal of molecular sciences · 2026Article
- Article
- The lung-brain axis in neurodegeneration: inflammatory, immune, and vascular mechanisms with therapeutic implications.Inflammopharmacology · 2026Review
- Expansion Revealing of Pathology Resolves Nanostructures Associated with Inflammatory Phenotypes in COVID-19 Decedent Human Brain Tissue.bioRxiv : the preprint server for biology · 2026Article
- Spike RBD drives sustained Parkinson's disease progression via microglia-neuron crosstalk-mediated RTP801 upregulation.Journal of advanced research · 2026Article
- SARS-CoV-2 Spike Protein S1 Subunit Induces Neuroinflammation Via Microglial Kv1.3 Channel.Biological psychiatry global open science · 2026Article
- SARS-CoV-2 Spike Protein Induces Time-Dependent and Brain-Region-Specific Alterations in Ferroptosis Markers: A Preliminary Study in K18-hACE2 Mice.International journal of molecular sciences · 2026Article
- Potential Impact of SARS-CoV-2 Spike Protein on HIV-1 Reservoir in People Living with HIV.Viruses · 2026Review
- 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
- Persistent neurological and behavioral alterations after SARS-CoV-2 infection in an optimized K18-hACE2 mouse model.Frontiers in microbiology · 2026Article
- Decoding long COVID-associated cardiovascular dysfunction: Mechanisms, models, and new approach methodologies.Journal of molecular and cellular cardiology · 2025Review
- Brain Volumetric Changes Post-COVID-19: A Systematic Review.Brain sciences · 2025Review
- Isolation and Characterization of a Novel Thermostable Bacteriophage Targeting Multi-Drug-ResistantViruses · 2025Article
- SARS-CoV-2 spike triggers TLR7-dependent endolysosome dysfunction and senescence in human astrocytes.Journal of neuroinflammation · 2025Article
- Caspases and brain-derived Neurotrophic Factor Levels and their Correlations with Psychiatric Symptoms in post-COVID-19.Neurotoxicity research · 2025Article
- Article
- Translating animal models of SARS-CoV-2 infection to vascular, neurological and gastrointestinal manifestations of COVID-19.Disease models & mechanisms · 2025Review
- Do Long COVID and COVID Vaccine Side Effects Share Pathophysiological Picture and Biochemical Pathways?International journal of molecular sciences · 2025Review
201 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
10 authors at 3 institutions in 1 country.
Funding
Abstract
It is unclear whether severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019, can enter the brain. Severe acute respiratory syndrome coronavirus 2 binds to cells via the S1 subunit of its spike protein. We show that intravenously injected radioiodinated S1 (I-S1) readily crossed the blood-brain barrier in male mice, was taken up by brain regions and entered the parenchymal brain space. I-S1 was also taken up by the lung, spleen, kidney and liver. Intranasally administered I-S1 also entered the brain, although at levels roughly ten times lower than after intravenous administration. APOE genotype and sex did not affect whole-brain I-S1 uptake but had variable effects on uptake by the olfactory bulb, liver, spleen and kidney. I-S1 uptake in the hippocampus and olfactory bulb was reduced by lipopolysaccharide-induced inflammation. Mechanistic studies indicated that I-S1 crosses the blood-brain barrier by adsorptive transcytosis and that murine angiotensin-converting enzyme 2 is involved in brain and lung uptake, but not in kidney, liver or spleen uptake.
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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.