Discovery of a novel SARS-CoV-2 cell entry mechanism mediated by circulating soluble ACE2 (sACE2): potential therapeutic target and risk marker for COVID-19

Dr Teng, Lee Lee   (Principal Investigator (PI))

Dr Yeung Man Lung   (Co-Investigator)

Professor WOO Patrick Chiu Yat   (Co-Investigator)

Dr Chan Elaine   (Co-Investigator)

24

2022-01-08

1113540

Discovery of a novel SARS-CoV-2 cell entry mechanism mediated by circulating soluble ACE2 (sACE2): potential therapeutic target and risk marker for COVID-19

cell entry, celllular ACE2 (cACE2), risk marker, SARS-CoV-2, soluble ACE2 (sACE2), therapeutics

Others - Medicine, Dentistry and Health

20190742

Health and Medical Research Fund - Full Grant

2020

On-going

Objectives: To elucidate the role of sACE2 in SARS-CoV-2 susceptibility and explore its potential applications, we aim to (1) dissect the role of sACE2 in SARS-CoV-2 infection; (2) investigate the effect of ACE2 shedding on SARS-CoV-2; (3) elucidate the relationship among viral load, cACE2 and sACE2 expressions in SARS-CoV-2-infected patients and (4) measure the sACE2 and cACE2 expressions using in-vitro and ex-vivo culture models. Hypothesis: Tissue tropism of SARS-CoV-2 cannot be fully explained by expression patterns of the receptor ACE2. Two forms of ACE2, cellular ACE2 (cACE2) and soluble ACE2 (sACE2), have been identified. While most studies focus on the function of cACE2, the role of sACE2 is unknown. Our recent findings uncovered a novel SARS-CoV-2 cell entry mechanism mediated by sACE2. We hypothesize that sACE2 plays an important role in SARS-CoV-2 infection, and that sACE2 level is positively correlated with the viral load in SARS-CoV-2-infected patients. We also hypothesize that population with higher sACE2 expression is at higher risk of contracting COVID-19. Design/subjects: Susceptibilities of different human cells to SARS-CoV-2 will be tested. Viral load/sACE2/cACE2 expressions will be measured. The shedding effect of ACE2 using various inhibitors on SARS-CoV-2 replication will be assessed. Instruments/interventions/main outcome measures: NA Data analysis/expected results: We will provide evidence that sACE2 is crucial for SARS-CoV-2 infection. Targeting the shedding of ACE2 will contribute to therapeutic drug development for COVID-19. Measurement of sACE2 expression in patients will offer insight towards which population are at increased risk of contracting COVID-19, suggesting higher priority for SARS-CoV-2 vaccine.