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

Man Lung Yeung*, Jade Lee Lee Teng, Lilong Jia, Chaoyu Zhang, Chengxi Huang, Jian Piao Cai, Runhong Zhou, Kwok Hung Chan, Hanjun Zhao, Lin Zhu, Kam Leung Siu, Sin Yee Fung, Susan Yung, Tak Mao Chan, Kelvin Kai Wang To, Jasper Fuk Woo Chan, Zongwei Cai, Susanna Kar Pui Lau, Zhiwei Chen, Dong Yan JinPatrick Chiu Yat Woo*, Kwok Yung Yuen*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

195 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2212-2228
Number of pages17
Issue number8
Publication statusPublished - 15 Apr 2021

Scopus Subject Areas

  • Biochemistry, Genetics and Molecular Biology(all)

User-Defined Keywords

  • ACE2
  • COVID-19
  • RNAi
  • sACE2
  • SARS-CoV-2
  • vasopressin
  • virus dependency factor


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