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

Man Lung Yeung | Zendy; Jade L. L. Teng | Zendy; Lilong Jia | Zendy; Chaoyu Zhang | Zendy; Chengxi Huang | Zendy; JianPiao Cai | Zendy; Runhong Zhou | Zendy; KwokHung Chan | Zendy; Hanjun Zhao | Zendy; Lin Zhu | Zendy; KamLeung Siu | Zendy; SinYee Fung | Zendy; Susan Yung | Zendy; Tak Mao Chan | Zendy; Kelvin KaiWang To | Zendy; Jasper FukWoo Chan | Zendy; Zongwei Cai | Zendy; Susanna Kar Pui Lau | Zendy; Zhiwei Chen | Zendy; DongYan Jin | Zendy; Patrick C. Y. Woo | Zendy; KwokYung Yuen | Zendy

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

Author(s) -

Man Lung Yeung,

Jade L. L. Teng,

Lilong Jia,

Chaoyu Zhang,

Chengxi Huang,

JianPiao Cai,

Runhong Zhou,

KwokHung Chan,

Hanjun Zhao,

Lin Zhu,

KamLeung Siu,

SinYee Fung,

Susan Yung,

Tak Mao Chan,

Kelvin KaiWang To,

Jasper FukWoo Chan,

Zongwei Cai,

Susanna Kar Pui Lau,

Zhiwei Chen,

DongYan Jin,

Patrick C. Y. Woo,

KwokYung Yuen

Publication year - 2021

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2021.02.053

Subject(s) - biology , renin–angiotensin system , peptidyl dipeptidase a , virology , cell , angiotensin converting enzyme 2 , covid-19 , microbiology and biotechnology , biochemistry , endocrinology , medicine , disease , blood pressure , infectious disease (medical specialty) , outbreak

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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