Soluble ACE2-mediated cell entry of SARS-CoV-2 via interaction with proteins related to the renin-angiotensin system.

Cell
Man Lung YeungKwok-Yung Yuen

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause acute respiratory disease and multiorgan failure. Finding human host factors that are essential for SARS-CoV-2 infection could facilitate the formulation of treatment strategies. Using a human kidney cell line-HK-2-that is highly susceptible to SARS-CoV-2, we performed a genome-wide RNAi screen and identified virus dependency factors (VDFs), which play regulatory roles in biological pathways linked to clinical manifestations of SARS-CoV-2 infection. We found a role for a secretory form of SARS-CoV-2 receptor, soluble angiotensin converting enzyme 2 (sACE2), in SARS-CoV-2 infection. Further investigation revealed that SARS-CoV-2 exploits receptor-mediated endocytosis through interaction between its spike with sACE2 or sACE2-vasopressin via AT1 or AVPR1B, respectively. Our identification of VDFs and the regulatory effect of sACE2 on SARS-CoV-2 infection shed insight into pathogenesis and cell entry mechanisms of SARS-CoV-2 as well as potential treatment strategies for COVID-19.

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Citations

Mar 25, 2021·Nature Reviews. Nephrology·Susan Allison
May 1, 2021·International Journal of Molecular Sciences·Agnieszka PawlosEwelina Woźniak
May 12, 2021·Proteins·Wenyang Jing, Erik Procko
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Sep 3, 2021·Nature Microbiology·Jim BaggenDirk Daelemans
Sep 14, 2021·Journal of Biomolecular Structure & Dynamics·Gérard Vergoten, Christian Bailly

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Datasets Mentioned

BETA
GSE159272

Methods Mentioned

BETA
pull-down
co-immunoprecipitation
confocal microscopy
biopsies
FCS
PCR
electrophoresis

Software Mentioned

PANTHER ( Protein Analysis Through Evolutionary Relationships )
R
GraphPad Prism
xGen
FISHER
Bowtie2
iHop
HTSeq
DESeq2
DAVID GO Cellular Component

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