tetano
Editor, Senior Moderator
Nat Struct Mol Biol
. 2021 Jan 11.
doi: 10.1038/s41594-020-00549-3. Online ahead of print.
A trimeric human angiotensin-converting enzyme 2 as an anti-SARS-CoV-2 agent
Tianshu Xiao[SUP] 1 2 [/SUP], Jianming Lu[SUP] 3 [/SUP], Jun Zhang[SUP] 1 2 [/SUP], Rebecca I Johnson[SUP] 4 [/SUP], Lindsay G A McKay[SUP] 4 [/SUP], Nadia Storm[SUP] 4 [/SUP], Christy L Lavine[SUP] 5 [/SUP], Hanqin Peng[SUP] 1 [/SUP], Yongfei Cai[SUP] 1 2 [/SUP], Sophia Rits-Volloch[SUP] 1 [/SUP], Shen Lu[SUP] 3 [/SUP], Brian D Quinlan[SUP] 6 [/SUP], Michael Farzan[SUP] 6 [/SUP], Michael S Seaman[SUP] 5 [/SUP], Anthony Griffiths[SUP] 4 [/SUP], Bing Chen[SUP] 7 8 [/SUP]
Affiliations
Abstract
Effective intervention strategies are urgently needed to control the COVID-19 pandemic. Human angiotensin-converting enzyme 2 (ACE2) is a membrane-bound carboxypeptidase that forms a dimer and serves as the cellular receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ACE2 is also a key negative regulator of the renin-angiotensin system that modulates vascular functions. We report here the properties of a trimeric ACE2 ectodomain variant, engineered using a structure-based approach. The trimeric ACE2 variant has a binding affinity of ~60 pM for the spike protein of SARS‑CoV‑2 (compared with 77 nM for monomeric ACE2 and 12-22 nM for dimeric ACE2 constructs), and its peptidase activity and the ability to block activation of angiotensin II receptor type 1 in the renin-angiotensin system are preserved. Moreover, the engineered ACE2 potently inhibits SARS‑CoV‑2 infection in cell culture. These results suggest that engineered, trimeric ACE2 may be a promising anti-SARS-CoV-2 agent for treating COVID-19.
. 2021 Jan 11.
doi: 10.1038/s41594-020-00549-3. Online ahead of print.
A trimeric human angiotensin-converting enzyme 2 as an anti-SARS-CoV-2 agent
Tianshu Xiao[SUP] 1 2 [/SUP], Jianming Lu[SUP] 3 [/SUP], Jun Zhang[SUP] 1 2 [/SUP], Rebecca I Johnson[SUP] 4 [/SUP], Lindsay G A McKay[SUP] 4 [/SUP], Nadia Storm[SUP] 4 [/SUP], Christy L Lavine[SUP] 5 [/SUP], Hanqin Peng[SUP] 1 [/SUP], Yongfei Cai[SUP] 1 2 [/SUP], Sophia Rits-Volloch[SUP] 1 [/SUP], Shen Lu[SUP] 3 [/SUP], Brian D Quinlan[SUP] 6 [/SUP], Michael Farzan[SUP] 6 [/SUP], Michael S Seaman[SUP] 5 [/SUP], Anthony Griffiths[SUP] 4 [/SUP], Bing Chen[SUP] 7 8 [/SUP]
Affiliations
- PMID: 33432247
- DOI: 10.1038/s41594-020-00549-3
Abstract
Effective intervention strategies are urgently needed to control the COVID-19 pandemic. Human angiotensin-converting enzyme 2 (ACE2) is a membrane-bound carboxypeptidase that forms a dimer and serves as the cellular receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ACE2 is also a key negative regulator of the renin-angiotensin system that modulates vascular functions. We report here the properties of a trimeric ACE2 ectodomain variant, engineered using a structure-based approach. The trimeric ACE2 variant has a binding affinity of ~60 pM for the spike protein of SARS‑CoV‑2 (compared with 77 nM for monomeric ACE2 and 12-22 nM for dimeric ACE2 constructs), and its peptidase activity and the ability to block activation of angiotensin II receptor type 1 in the renin-angiotensin system are preserved. Moreover, the engineered ACE2 potently inhibits SARS‑CoV‑2 infection in cell culture. These results suggest that engineered, trimeric ACE2 may be a promising anti-SARS-CoV-2 agent for treating COVID-19.