A trimeric human angiotensin-converting enzyme 2 as an anti-SARS-CoV-2 agent.

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.
Mesh Terms:
Angiotensin-Converting Enzyme 2, Antiviral Agents, COVID-19, Cryoelectron Microscopy, Humans, Models, Molecular, Protein Engineering, Protein Multimerization, Recombinant Proteins, SARS-CoV-2
Nat Struct Mol Biol
Date: Dec. 01, 2020
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