National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
AI147884
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
AI147884 01A1S1
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
AI141002
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
AI127193
米国
引用
ジャーナル: bioRxiv / 年: 2020 タイトル: A trimeric human angiotensin-converting enzyme 2 as an anti-SARS-CoV-2 agent in vitro. 著者: Tianshu Xiao / Jianming Lu / Jun Zhang / Rebecca I Johnson / Lindsay G A McKay / Nadia Storm / Christy L Lavine / Hanqin Peng / Yongfei Cai / Sophia Rits-Volloch / Shen Lu / Brian D Quinlan / ...著者: Tianshu Xiao / Jianming Lu / Jun Zhang / Rebecca I Johnson / Lindsay G A McKay / Nadia Storm / Christy L Lavine / Hanqin Peng / Yongfei Cai / Sophia Rits-Volloch / Shen Lu / Brian D Quinlan / Michael Farzan / Michael S Seaman / Anthony Griffiths / Bing Chen 要旨: Effective intervention strategies are urgently needed to control the COVID-19 pandemic. Human angiotensin-converting enzyme 2 (ACE2) is a carboxypeptidase that forms a dimer and serves as the ...Effective intervention strategies are urgently needed to control the COVID-19 pandemic. Human angiotensin-converting enzyme 2 (ACE2) is a carboxypeptidase that forms a dimer and serves as the cellular receptor for SARS-CoV-2. It is also a key negative regulator of the renin-angiotensin system (RAS), conserved in mammals, which modulates vascular functions. We report here the properties of a trimeric ACE2 variant, created by a structure-based approach, with binding affinity of ~60 pM for the spike (S) protein of SARS-CoV-2, while preserving the wildtype peptidase activity as well as the ability to block activation of angiotensin II receptor type 1 in the RAS. Moreover, the engineered ACE2 potently inhibits infection of SARS-CoV-2 in cell culture. These results suggest that engineered, trimeric ACE2 may be a promising anti-SARS-CoV-2 agent for treating COVID-19.