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.
【초록키워드】 SARS-CoV-2, ACE2, coronavirus, COVID-19 pandemic, Human, variant, Infection, Intervention, severe acute respiratory syndrome Coronavirus, anti-SARS-CoV-2, angiotensin-converting enzyme 2, binding affinity, Spike protein, renin-angiotensin system, Cell culture, receptor, respiratory, Human angiotensin-converting enzyme 2, Angiotensin II, angiotensin, acute respiratory syndrome, Activation, Renin, Vascular, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, human Angiotensin-converting enzyme, dimer, functions, ectodomain, treating COVID-19, cellular receptor, membrane-bound, approach, trimeric, inhibit, form, the spike protein, modulate, dimeric, monomeric, preserved, 【제목키워드】 anti-SARS-CoV-2, trimeric,