SARS-CoV-2 Spike Protein S1 Subunit Induces Neuroinflammation Via Microglial Kv1.3 Channel
et al., Biological Psychiatry Global Open Science, doi:10.1016/j.bpsgos.2026.100716, May 2026
Mouse study showing that the SARS-CoV-2 spike protein S1 subunit induces neuroinflammation via microglial Kv1.3 channel activation, and that chlorpromazine (CPZ) mitigates these effects.
Lee et al., 31 May 2026, peer-reviewed, 4 authors.
Abstract: ## Archival Report
SARS-CoV-2 Spike Protein S1 Subunit Induces Neuroinflammation Via Microglial Kv1.3 Channel
Hee-Yoon Lee, Young Lee, Su-Hyun Jo, and Se-Young Choi
ABSTRACT
BACKGROUND: Neuroinflammation is a hallmark of various neurological and psychiatric disorders, including postCOVID-19 conditions caused by SARS-CoV-2 infection. The S1 subunit of the SARS-CoV-2 spike protein (S1 protein) can trigger neuroinflammation by activating microglia. However, the precise mechanism of S1 proteininduced microglial activation remains unclear. Our investigation revealed that the Kv1.3 channel plays a role in S1 protein-mediated neuroinflammation.
METHODS: We performed whole-cell patch clamp recording of microglia in CX3CR1 GFP/ 1 mice, Iba1 immunohistochemistry analysis, and behavioral analysis.
RESULTS: We found that the S1 protein increased Kv1.3 channel activity and microglial activation in the lateral septum, leading to behavioral changes. Chlorpromazine (CPZ), an antipsychotic linked to lower COVID-19 rates in clinical observations, blocked S1 protein-mediated increase in Kv1.3 channel current and microglia size. Mice injected with the S1 protein showed anxiety-like behavior, which CPZ alleviated.
CONCLUSIONS: This study elucidates the molecular mechanism of S1 protein-mediated neuroinflammation and CPZ as a potential treatment for post-COVID symptoms.
[https://doi.org/10.1016/j.bpsgos.2026.100716](https://doi.org/10.1016/j.bpsgos.2026.100716)
COVID-19, caused by SARS-CoV-2, primarily affects the respiratory tract but can also lead to severe neurological and psychiatric symptoms by reaching the central nervous system (CNS) (1). Post-COVID syndrome or long COVID have been reported to include fatigue, depression, and anxiety (2,3). In fact, COVID-19 infections are significant risk factors for a chronic neuroinflammation-related disease, which is linked to many neurological and psychiatric diseases (4-7). Neuroinflammation is thought to be associated with Alzheimer's disease (8), schizophrenia (9,10), and depression (11). Conversely, patients with Alzheimer's disease show significant microglial dysregulation and are more sensitive to a severe systemic SARS-CoV-2 infection (12).
Microglia, the CNS's resident immune cells, release proinflammatory cytokines and mediate neuroinflammation when activated by injury or pathogens (13,14). This activation is observed in patients with COVID-19 (15) when the spike protein S1 subunit of the SARS-CoV-2 virus (S1 protein) is found in plasma during SARS-CoV-2 infection (16). The S1 subunit of the spike protein is known to bind to angiotensinconverting enzyme 2 and to facilitate viral entry into the host cell (17,18). However, mounting evidence indicates that the S1 protein could induce neuroinflammation through microglial activation (19-21). Injection of S1 protein in mice results in increased Iba1 expression, proinflammatory cytokines (22,23), and reactive oxygen species in microglia (24,25). Additionally, the S1 protein binds to fibrin, forming proinflammatory blood clots that promote systemic thromboinflammation and microglial activation (26). The S1 protein also activates monocytes to release cytokines (27). However, it is still unclear through what mechanism the S1 protein induces microglia activation. Recently, it has been revealed that various ion..
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"DOI": "10.1007/s12035-021-02696-0",
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"author": "Frank",
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"DOI": "10.3389/fimmu.2021.656700",
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"DOI": "10.3389/fphar.2020.577678",
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"DOI": "10.1055/a-1717-2381",
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"DOI": "10.1126/science.3854",
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"doi-asserted-by": "crossref",
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"DOI": "10.1038/nrn.2016.57",
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"DOI": "10.1016/j.euroneuro.2004.04.002",
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"DOI": "10.1007/s12035-021-02542-3",
"article-title": "Phenothiazine inhibits neuroinflammation and inflammasome activation independent of hypothermia after ischemic stroke",
"author": "Guo",
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"first-page": "573",
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"year": "2020"
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"DOI": "10.1016/S0006-8993(98)00227-3",
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"first-page": "3053",
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"DOI": "10.1038/s41467-022-29440-z",
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"DOI": "10.1016/j.brainresrev.2004.04.009",
"article-title": "Regulation of affect by the lateral septum: Implications for neuropsychiatry",
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