About: The S1 protein of SARS-CoV-2 crosses the blood-brain barrier: Kinetics, distribution, mechanisms, and influence of ApoE genotype, sex, and inflammation

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About: The S1 protein of SARS-CoV-2 crosses the blood-brain barrier: Kinetics, distribution, mechanisms, and influence of ApoE genotype, sex, and inflammation Goto Sponge NotDistinct Permalink

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	The S1 protein of SARS-CoV-2 crosses the blood-brain barrier: Kinetics, distribution, mechanisms, and influence of ApoE genotype, sex, and inflammation
Creator	Banks1, William Baumann1, Kristen Erickson1, Michelle Hansen1, Kim Holden3, Sarah Logsdon1, Aric Raber3, Jacob Reed1, May Rhea1, Elizabeth Williams1, Lindsey
Source	BioRxiv
abstract	Evidence strongly suggests that SARS-CoV-2, the cause of COVID-19, can enter the brain. SARS-CoV-2 enters cells via the S1 subunit of its spike protein, and S1 can be used as a proxy for the uptake patterns and mechanisms used by the whole virus; unlike studies based on productive infection, viral proteins can be used to precisely determine pharmacokinetics and biodistribution. Here, we found that radioiodinated S1 (I-S1) readily crossed the murine blood-brain barrier (BBB). I-S1 from two commercial sources crossed the BBB with unidirectional influx constants of 0.287 ± 0.024 μL/g-min and 0.294 ± 0.032 μL/g-min and was also taken up by lung, spleen, kidney, and liver. I-S1 was uniformly taken up by all regions of the brain and inflammation induced by lipopolysaccharide reduced uptake in the hippocampus and olfactory bulb. I-S1 crossed the BBB completely to enter the parenchymal brain space, with smaller amounts retained by brain endothelial cells and the luminal surface. Studies on the mechanisms of transport indicated that I-S1 crosses the BBB by the mechanism of adsorptive transcytosis and that the murine ACE2 receptor is involved in brain and lung uptake, but not that by kidney, liver, or spleen. I-S1 entered brain after intranasal administration at about 1/10th the amount found after intravenous administration and about 0.66% of the intranasal dose entered blood. ApoE isoform or sex did not affect whole brain uptake, but had variable effects on olfactory bulb, liver, spleen, and kidney uptakes. In summary, I-S1 readily crosses the murine BBB, entering all brain regions and the peripheral tissues studied, likely by the mechanism of adsorptive transcytosis. Graphical Abstract
has issue date	2020-07-15(xsd:dateTime)
bibo:doi	10.1101/2020.07.15.205229
has license	biorxiv
sha1sum (hex)	2054614db252264f5cba93e05ca3282726aae560
schema:url	https://doi.org/10.1101/2020.07.15.205229
resource representing a document's title	The S1 protein of SARS-CoV-2 crosses the blood-brain barrier: Kinetics, distribution, mechanisms, and influence of ApoE genotype, sex, and inflammation
schema:publication	bioRxiv
resource representing a document's body	covid:2054614db252264f5cba93e05ca3282726aae560#body_text
is schema:about of	named entity 'COVID-19' named entity 'crosses' named entity 'endothelial cells' named entity 'ApoE' named entity 'protein' named entity 'COMPLETELY' named entity 'AFFECT' named entity 'ADL' named entity 'UNIDIRECTIONAL' named entity 'constants' named entity 'liver' named entity 'spleen' named entity 'crossed' named entity 'effects' named entity 'mechanism' named entity 'transcytosis' named entity 'completely' named entity 'determine' named entity 'crossed' named entity 'dose' named entity 'inflammation' named entity 'iBEC' named entity 'intravenous administration' named entity 'anesthetized' named entity 'endothelial cells' named entity 'SARS-CoV-2' named entity 'lung' named entity 'kidney' named entity 'precipitate' named entity 'lactated Ringer's solution' named entity 'LPS' named entity 'ApoE4' named entity 'serum' named entity 'ACE2' named entity 'spleen' named entity 'liver' named entity 'kidney' named entity 'lung' named entity 'entered' named entity 'SARS-CoV-2' named entity 'spleen' named entity 'kidney' named entity 'hippocampus' named entity 'liver' named entity 'BBB' named entity 'transcytosis' named entity 'olfactory bulb' named entity 'liver' named entity 'protein' named entity 'Serum' named entity 'multiple comparison' named entity 'cell line' named entity 'Radioactivity' named entity 'cerebellum' named entity 'transcytosis' named entity 'radioactivity' named entity 'HIV-1' named entity 'adsorptive' named entity 'One-way ANOVA' named entity 'serum levels' named entity 'albumin' named entity 'cytokine storm' named entity 'kidney' named entity 'olfactory bulb' named entity 'radioactivity' named entity 'Inflammation' named entity 'multiple comparisons' named entity 'statistical significance' named entity 'luminal' named entity 'parenchyma' named entity 'liver' named entity 'LPS' named entity '4.2' named entity 'radioactivity' named entity 'luminal'

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