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

Nature Structural & Molecular Biology
Tianshu XiaoBing Chen

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.

References

Jul 8, 2005·Nature·Yumiko ImaiJosef M Penninger
Jan 14, 2010·Biotechnology Journal·Simona JevsevarVladka Gaberc Porekar
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Nov 26, 2010·Current Opinion in Nephrology and Hypertension·Chris TikellisWendy C Burns
Dec 15, 2010·Drug Discovery Today·Chiranjib Dasgupta, Lubo Zhang
Nov 29, 2011·International Journal of Hypertension·Nicola E Clarke, Anthony J Turner
Sep 25, 2012·Journal of Structural Biology·Sjors H W Scheres
Sep 17, 2013·ELife·Andrew MorinPiotr Sliz
Aug 19, 2015·Journal of Structural Biology·Alexis Rohou, Nikolaus Grigorieff
Mar 11, 2017·Nature Communications·Urvashi SharmaDavid J S Hulmes
Sep 8, 2017·Critical Care : the Official Journal of the Critical Care Forum·Akram KhanAili L Lazaar
Jun 7, 2018·Acta Crystallographica. Section D, Structural Biology·Tristan Ian Croll
Jun 16, 2018·The European Respiratory Journal·Anna R HemnesJames West
Jun 27, 2019·Communications Biology·Thorsten WagnerStefan Raunser
Jan 8, 2020·JAMA : the Journal of the American Medical Association·Lisa SandersGordon D Schiff
Jan 12, 2020·Communications Biology·Thorsten WagnerStefan Raunser
Feb 13, 2020·Cellular & Molecular Immunology·Shuai XiaLu Lu
Feb 23, 2020·Science·Daniel WrappJason S McLellan
Mar 11, 2020·Cell·Alexandra C WallsDavid Veesler
Mar 29, 2020·JAMA : the Journal of the American Medical Association·Chenguang ShenLei Liu
Apr 1, 2020·Nature·Jian ShangFang Li
Apr 8, 2020·Proceedings of the National Academy of Sciences of the United States of America·Kai DuanXiaoming Yang
Apr 8, 2020·The Journal of Clinical Investigation·Evan M BlochAaron Ar Tobian
May 13, 2020·Current Pharmacology Reports·Renyi WuAh-Ng Kong
Jun 4, 2020·The New England Journal of Medicine·David R BoulwareKathy H Hullsiek
Jun 24, 2020·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Samuel B PolakJudith van Paassen
Jul 23, 2020·Science·Yongfei CaiBing Chen

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Citations

Feb 25, 2021·Nature Biotechnology·Ruili HuangWei Zheng
Apr 17, 2021·Frontiers in Cellular and Infection Microbiology·Ashok KumarNiraj Kumar
May 9, 2021·Cardiovascular Diabetology·Nunzia D'OnofrioRaffaele Marfella
May 12, 2021·Proteins·Wenyang Jing, Erik Procko
Jul 29, 2021·Clinical Microbiology Reviews·Kaiming TaoRobert W Shafer
Aug 14, 2021·Nature Structural & Molecular Biology·Tzu-Jing YangShang-Te Danny Hsu
Aug 29, 2021·Viruses·Sébastien Calvignac-SpencerMartin Hölzer
Aug 31, 2021·Frontiers in Molecular Biosciences·Fabrizio CleriRalf Blossey

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Methods Mentioned

BETA
gel filtration
bio-layer
surface plasmon resonance
PCR
transfection
biosensors
Assay

Clinical Trials Mentioned

NCT04335136
NCT00886353

Software Mentioned

ISOLDE
GraphPad Prism
SerialEM
SBGrid
RELION
Phenix
Octet Data Analysis HT
MotionCor2
RELION3
CTFFIND4

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