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.
Endothelin-1 stimulates the in vitro release of neurohypophyseal hormones, but not corticotropin-releasing hormone, via ETA receptors
Bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPases, inhibits the receptor-mediated endocytosis of asialoglycoproteins in isolated rat hepatocytes
The long and the short cycle. Alternative intracellular routes for trafficking of G-protein-coupled receptors
Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis
NCBI Reference Sequence (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins
Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2).
DAVID Bioinformatics Resources: expanded annotation database and novel algorithms to better extract biology from large gene lists
Modulation of TNF-alpha-converting enzyme by the spike protein of SARS-CoV and ACE2 induces TNF-alpha production and facilitates viral entry
Roles for microRNAs, miR-93 and miR-130b, and tumor protein 53-induced nuclear protein 1 tumor suppressor in cell growth dysregulation by human T-cell lymphotrophic virus 1
A genome-wide short hairpin RNA screening of jurkat T-cells for human proteins contributing to productive HIV-1 replication
Angiotensin II-stimulated secretion of arginine vasopressin is inhibited by atrial natriuretic peptide in humans
Influenza and SARS-coronavirus activating proteases TMPRSS2 and HAT are expressed at multiple sites in human respiratory and gastrointestinal tracts
Angiotensin II mediates angiotensin converting enzyme type 2 internalization and degradation through an angiotensin II type I receptor-dependent mechanism.
Attenuation of ligand-induced activation of angiotensin II type 1 receptor signaling by the type 2 receptor via protein kinase C
Effect of Chronic Kidney Disease on Changes in Vasopressin System Expression in the Kidney Cortex in Rats with Nephrectomy
PANTHER version 14: more genomes, a new PANTHER GO-slim and improvements in enrichment analysis tools
Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus
Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study
Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection.
SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes.
Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2.
Regulated Intramembrane Proteolysis of ACE2: A Potential Mechanism Contributing to COVID-19 Pathogenesis?
Potent prophylactic and therapeutic efficacy of recombinant human ACE2-Fc against SARS-CoV-2 infection in vivo.
Vasopressin infusion in COVID-19 critical illness is not associated with impaired viral clearance: a pilot study.
Distinct Regulation of U-ACE2 and P-ACE2 (Urinary and Plasma Angiotensin-Converting Enzyme 2) in a Japanese General Population.
The impact of spike N501Y mutation on neutralizing activity and RBD binding of SARS-CoV-2 convalescent serum.
Protocol for the Controlled evaLuation of Angiotensin Receptor blockers for COVID-19 respIraTorY disease (CLARITY): a randomised controlled trial.
Interaction of the renin inhibitor aliskiren with the SARS-CoV-2 main protease: a molecular docking study.
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