@article {Xiao2021, title = {A trimeric human angiotensin-converting enzyme 2 as an anti-SARS-CoV-2 agent}, journal = {Nature Structural \& Molecular Biology}, year = {2021}, month = {Jan}, 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{\textendash}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 \textasciitilde60{\th}inspace}pM for the spike protein of SARS-CoV-2 (compared with 77{\th}inspace}nM for monomeric ACE2 and 12{\textendash}22{\th}inspace}nM for dimeric ACE2 constructs), and its peptidase activity and the ability to block activation of angiotensin II receptor type 1 in the renin{\textendash}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.}, issn = {1545-9985}, doi = {10.1038/s41594-020-00549-3}, url = {https://doi.org/10.1038/s41594-020-00549-3}, author = {Xiao, Tianshu and Lu, Jianming and Zhang, Jun and Johnson, Rebecca I. and McKay, Lindsay G. A. and Storm, Nadia and Lavine, Christy L. and Peng, Hanqin and Cai, Yongfei and Rits-Volloch, Sophia and Lu, Shen and Quinlan, Brian D. and Farzan, Michael and Seaman, Michael S. and Griffiths, Anthony and Chen, Bing} }