Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2.

Cell
Vanessa MonteilJosef M Penninger

Abstract

We have previously provided the first genetic evidence that angiotensin converting enzyme 2 (ACE2) is the critical receptor for severe acute respiratory syndrome coronavirus (SARS-CoV), and ACE2 protects the lung from injury, providing a molecular explanation for the severe lung failure and death due to SARS-CoV infections. ACE2 has now also been identified as a key receptor for SARS-CoV-2 infections, and it has been proposed that inhibiting this interaction might be used in treating patients with COVID-19. However, it is not known whether human recombinant soluble ACE2 (hrsACE2) blocks growth of SARS-CoV-2. Here, we show that clinical grade hrsACE2 reduced SARS-CoV-2 recovery from Vero cells by a factor of 1,000-5,000. An equivalent mouse rsACE2 had no effect. We also show that SARS-CoV-2 can directly infect engineered human blood vessel organoids and human kidney organoids, which can be inhibited by hrsACE2. These data demonstrate that hrsACE2 can significantly block early stages of SARS-CoV-2 infections.

Associated Clinical Trials

References

Jan 1, 1989·Annual Review of Medicine·L G Dobbs
Jun 21, 2002·Nature·Michael A CrackowerJosef M Penninger
Apr 12, 2003·The New England Journal of Medicine·Christian DrostenHans Wilhelm Doerr
Oct 22, 2004·Proceedings of the National Academy of Sciences of the United States of America·Scott A JeffersKathryn V Holmes
Jul 8, 2005·Nature·Yumiko ImaiJosef M Penninger
Jul 27, 2005·The Journal of Experimental Medicine·Jiang GuAnthony S-Y Leong
Mar 4, 2006·Circulation Research·Ursula Danilczyk, Josef M Penninger
Nov 28, 2008·Proceedings of the National Academy of Sciences of the United States of America·Michelle M BeckerMark R Denison
Nov 29, 2011·International Journal of Hypertension·Nicola E Clarke, Anthony J Turner
Aug 30, 2012·Nature Methods·Caroline A SchneiderKevin W Eliceiri
Aug 31, 2016·Nature Microbiology·Man-Lung YeungKwok-Yung Yuen
Sep 8, 2017·Critical Care : the Official Journal of the Critical Care Forum·Akram KhanAili L Lazaar
May 24, 2018·Bioinformatics·James HadfieldRichard A Neher
Jul 8, 2018·Journal of the American Society of Nephrology : JASN·Haojia WuBenjamin D Humphreys
Jan 18, 2019·Nature·Reiner A WimmerJosef M Penninger
Jun 11, 2019·Cell·Tim StuartRahul Satija
Jan 10, 2017·Global Challenges·Stefan Elbe, Gemma Buckland-Merrett
Jan 25, 2020·The New England Journal of Medicine·Na ZhuUNKNOWN China Novel Coronavirus Investigating and Research Team
Feb 23, 2020·Science·Daniel WrappJason S McLellan
Feb 29, 2020·The New England Journal of Medicine·Wei-Jie GuanUNKNOWN China Medical Treatment Expert Group for Covid-19
Mar 4, 2020·Nature Microbiology·UNKNOWN Coronaviridae Study Group of the International Committee on Taxonomy of Viruses
Mar 4, 2020·JAMA : the Journal of the American Medical Association·Barnaby Edward YoungUNKNOWN Singapore 2019 Novel Coronavirus Outbreak Research Team
Mar 23, 2020·Biochemical and Biophysical Research Communications·Furong QiZheng Zhang
Apr 15, 2020·Nature Medicine·Kristian G AndersenRobert F Garry
Dec 12, 2020·Cell·Alexandra C WallsDavid Veesler

❮ Previous
Next ❯

Citations

May 5, 2020·Microbial Biotechnology·Harald Brüssow
May 14, 2020·American Journal of Physiology. Endocrinology and Metabolism·Afif Nakhleh, Naim Shehadeh
May 21, 2020·JAMA : the Journal of the American Medical Association·Ankit B Patel, Ashish Verma
Apr 26, 2020·British Journal of Pharmacology·Krishna Sriram, Paul A Insel
May 10, 2020·Science·R Kiplin GuyRebecca E Dutch
Apr 14, 2020·Journal of Medical Virology·Hao ChengGui-Qiang Wang
May 6, 2020·British Journal of Pharmacology·Hong ZhouXiao-Ming Meng
Jun 11, 2020·Journal of Diabetes Science and Technology·David C Klonoff
Jun 17, 2020·Transfusion·Louis M Katz
Jun 5, 2020·British Journal of Pharmacology·Chiara ColarussoRosalinda Sorrentino
Jul 9, 2020·Alimentary Pharmacology & Therapeutics·Anand V KulkarniDuvvuru Nageshwar Reddy
May 29, 2020·Current Cardiology Reviews·Antonio Crisafulli, Pasquale Pagliaro
Jul 10, 2020·Journal of Biomolecular Structure & Dynamics·Fatma ElrashdyVladimir N Uversky
Jul 15, 2020·Human Vaccines & Immunotherapeutics·Abdolkarim Sheikhi, Mohammad Hojjat-Farsangi
Jul 16, 2020·Journal of Evaluation in Clinical Practice·Jeffrey K AronsonJon Williamson
Jun 12, 2020·International Journal of Cancer. Journal International Du Cancer·Tom Winkler, Uri Ben-David
Jun 15, 2020·Allergy·Carmen RiggioniCezmi A Akdis
Jun 26, 2020·Journal of the European Academy of Dermatology and Venereology : JEADV·P GisondiL Naldi
Jul 24, 2020·Journal of Drug Targeting·Saghir AkhtarAbdella M Habib
Jun 27, 2020·Circulation Research·James D McFadyenKarlheinz Peter
Jul 23, 2020·British Journal of Pharmacology·Claudia PennaPasquale Pagliaro
May 30, 2020·Aging·Amber L MuellerDavid A Sinclair
Aug 22, 2020·Stem Cells Translational Medicine·Abbas ShafieeJason Brown
Jul 15, 2020·Journal of Cardiac Surgery·Ali GhodsizadMatthias Loebe
Jul 30, 2020·Physiological Reviews·A SicaV Torri
Jul 14, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Nigel MackmanNigel S Key
Aug 29, 2020·Stem Cells Translational Medicine·Anthony AtalaJoshua Hunsberger
Aug 29, 2020·Clinical Obesity·See KwokAkheel A Syed
Aug 18, 2020·Clinical and Translational Science·Narjes Saheb Sharif-AskariRabih Halwani
Jul 15, 2020·American Journal of Respiratory and Critical Care Medicine·Yu ZhaoWei Zuo
Aug 28, 2020·Open Biology·Vanessa WaznyChristine Cheung
Sep 3, 2020·Journal of Nephrology·Niloofar Khoshdel-RadMassoud Vosough
Sep 3, 2020·Nanomedicine·Georgia Wilson JonesBengt Fadeel
Sep 5, 2020·Vision·Brad P BarnettDaniel Chao

❮ Previous
Next ❯

Datasets Mentioned

BETA
MT093571
GSM4447249

Methods Mentioned

BETA
Electron microscopy
light microscopy
light
confocal microscopy
RNA-Seq
gel filtration
FACS
scRNA-seq

Software Mentioned

ImageJ
GraphPad Prism
NextStrain
Cell Ranger
GraphPad
Seurat R package
Seurat
FACSDiva

Related Concepts

Related Feeds

Cell eTOC

Cell is a scientific journal publishing research across a broad range of disciplines within the life sciences field. Discover the latest research from Cell here.

Related Papers

Signal Transduction and Targeted Therapy
Tarek Mohamed Abd El-AzizJames D Stockand
Nature Reviews. Nephrology
Susan J Allison
Journal of Hypertension
Fabio AngeliPaolo Verdecchia
BioRxiv : the Preprint Server for Biology
Jessie Low-GanVaughn Smider
BioRxiv : the Preprint Server for Biology
J. L. GanVaughn V. Smider
© 2021 Meta ULC. All rights reserved