Susceptibility of human neural stem cells to SARS-CoV-2: Entry mechanisms and glycocalyx influence
- 1Department of Molecular, Cell, and Systems Biology, University of California, Riverside, California, United States of America.
- 2Department of Neuroscience, University of California, Riverside, California, United States of America.
Abstract
Previous work demonstrated that ectodermal cells exhibit greater susceptibility to SARS-CoV-2 than endodermal and mesodermal cells, raising concerns about potential vulnerability of the developing nervous system. We hypothesized that neural stem cells (NSCs) derived from human ectoderm are susceptible to SARS-CoV-2. Using pseudotyped viral particles representing both wild-type and Omicron spike variants, we confirmed efficient transduction in NSCs, with Omicron variants preferentially utilizing endocytosis-mediated entry. Inhibition of endocytosis with filipin and OcTMAB significantly reduced viral entry across all spike variants. Low glycosylation levels on NSCs facilitated viral entry, and enzymatic removal of glycosylation increased their susceptibility. Ectodermal infection by SARS-CoV-2 raises serious concern for potential teratogenic effects on the nervous system, possibly causing latent or subclinical anomalies not immediately evident at birth. Therefore, future clinical studies and long-term surveillance of infants and children exposed in utero are necessary to investigate and identify potential neurodevelopmental deficits.
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BibTeX
@article{song2026susceptibility,
title = {{Susceptibility of human neural stem cells to SARS-CoV-2: Entry mechanisms and glycocalyx influence}},
author = {Ann Song and Cori Zuvia and Prue Talbot},
journal = {PLOS One},
year = {2026},
month = oct,
doi = {10.1371/journal.pone.0360734},
url = {https://doi.org/10.1371/journal.pone.0360734},
note = {CC BY},
}
RIS
TY - JOUR
TI - Susceptibility of human neural stem cells to SARS-CoV-2: Entry mechanisms and glycocalyx influence
AU - Ann Song
AU - Cori Zuvia
AU - Prue Talbot
PY - 2026
DA - 2026/10/21
JO - PLOS One
DO - 10.1371/journal.pone.0360734
UR - https://doi.org/10.1371/journal.pone.0360734
AB - Previous work demonstrated that ectodermal cells exhibit greater susceptibility to SARS-CoV-2 than endodermal and mesodermal cells, raising concerns about potential vulnerability of the developing nervous system. We hypothesized that neural stem cells (NSCs) derived from human ectoderm are susceptible to SARS-CoV-2. Using pseudotyped viral particles representing both wild-type and Omicron spike variants, we confirmed efficient transduction in NSCs, with Omicron variants preferentially utilizing endocytosis-mediated entry. Inhibition of endocytosis with filipin and OcTMAB significantly reduced viral entry across all spike variants. Low glycosylation levels on NSCs facilitated viral entry, and enzymatic removal of glycosylation increased their susceptibility. Ectodermal infection by SARS-CoV-2 raises serious concern for potential teratogenic effects on the nervous system, possibly causing latent or subclinical anomalies not immediately evident at birth. Therefore, future clinical studies and long-term surveillance of infants and children exposed in utero are necessary to investigate and identify potential neurodevelopmental deficits.
SN - 1932-6203
ER -