Evidence map›Paper›PMID 37239978›Full record

ArticleInternational journal of molecular sciences2023

ACE-2, TMPRSS2, and Neuropilin-1 Receptor Expression on Human Brain Astrocytes and Pericytes and SARS-CoV-2 Infection Kinetics.

Johid Reza Malik, Arpan Acharya, Sean N Avedissian, Siddappa N Byrareddy, Courtney V Fletcher, Anthony T Podany, Shetty Ravi Dyavar

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
6.0field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 29 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Johid Reza MalikAntiviral Pharmacology Laboratory, Department of Pharmacy Practice and Science, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA.ORCID 0000-0001-5999-9187
Arpan AcharyaDepartment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Sean N AvedissianAntiviral Pharmacology Laboratory, Department of Pharmacy Practice and Science, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA.ORCID 0000-0002-0935-6455
Siddappa N ByrareddyDepartment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.ORCID 0000-0002-6889-4640
Courtney V FletcherAntiviral Pharmacology Laboratory, Department of Pharmacy Practice and Science, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA.ORCID 0000-0002-3703-7849
Anthony T PodanyAntiviral Pharmacology Laboratory, Department of Pharmacy Practice and Science, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Shetty Ravi DyavarAntiviral Pharmacology Laboratory, Department of Pharmacy Practice and Science, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA.ORCID 0000-0002-2141-7214
University of Nebraska Medical Center · USKarolinska Institutet · SE

Funding

Therapeutics Core (Page 286)P30MH062261 · NIMH · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI GENDELMAN, HOWARD E · 2000 to 2021
$37.7M
The Lymphoid Tissue Pharmacology of Antiretroviral DrugsR01AI124965 · NIAID · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI FLETCHER, COURTNEY V · 2016 to 2020
$3.7M
Investigations of antiretroviral therapy penetration in cerebrospinal fluidK23MH125734 · NIMH · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI AVEDISSIAN, SEAN · 2021 to 2025
$862k
NIAID NIH HHS R01 AI124965NIH HHS K23 MH125734NIH HHS R01-AI124965NIMH NIH HHS K23 MH125734NIMH NIH HHS NIMH P30 MH062261
6 · The paper itself

Abstract

Angiotensin Converting Enzyme 2 (ACE-2), Transmembrane Serine Protease 2 (TMPRSS-2) and Neuropilin-1 cellular receptors support the entry of SARS-CoV-2 into susceptible human target cells and are characterized at the molecular level. Some evidence on the expression of entry receptors at mRNA and protein levels in brain cells is available, but co-expression of these receptors and confirmatory evidence on brain cells is lacking. SARS-CoV-2 infects some brain cell types, but infection susceptibility, multiple entry receptor density, and infection kinetics are rarely reported in specific brain cell types. Highly sensitive Taqman ddPCR, flow-cytometry and immunocytochemistry assays were used to quantitate the expression of ACE-2, TMPRSS-2 and Neuropilin-1 at mRNA and protein levels on human brain-extracted pericytes and astrocytes, which are an integral part of the Blood-Brain-Barrier (BBB). Astrocytes showed moderate ACE-2 (15.9 ± 1.3%, Mean ± SD, n = 2) and TMPRSS-2 (17.6%) positive cells, and in contrast show high Neuropilin-1 (56.4 ± 39.8%, n = 4) protein expression. Whereas pericytes showed variable ACE-2 (23.1 ± 20.7%, n = 2), Neuropilin-1 (30.3 ± 7.5%, n = 4) protein expression and higher TMPRSS-2 mRNA (667.2 ± 232.3, n = 3) expression. Co-expression of multiple entry receptors on astrocytes and pericytes allows entry of SARS-CoV-2 and progression of infection. Astrocytes showed roughly four-fold more virus in culture supernatants than pericytes. SARS-CoV-2 cellular entry receptor expression and "in vitro" viral kinetics in astrocytes and pericytes may improve our understanding of viral infection "in vivo". In addition, this study may facilitate the development of novel strategies to counter the effects of SARS-CoV-2 and inhibit viral infection in brain tissues to prevent the spread and interference in neuronal functions.

Indexed as

COVID-19Angiotensin-Converting Enzyme 2AstrocytesBlood-Brain BarrierHumansKineticsNeuropilin-1PericytesSARS-CoV-2Serine EndopeptidasesAngiotensin-Converting Enzyme 2Neuropilin-1Serine EndopeptidasesTMPRSS2 protein, humanACE-2astrocytesbrain microvascular endothelial cells and blood-brain-barrierCOVID-19Neuropilin-1pericytesSARS-CoV-2TMPRSS-2

Identifiers

PMID37239978
PMCPMC10218482
OpenAlexW4376279203

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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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.