ACE2, the Receptor that Enables the Infection by SARS-CoV-2: Biochemistry, Structure, Allostery and Evaluation of the Potential Development of ACE2 Modulators

ChemMedChem
Lissy Z F GrossRicardo M Biondi

Abstract

Angiotensin Converting Enzyme 2 (ACE2) is the human receptor that interacts with the Spike protein of coronaviruses, including the one that produced the 2020 coronavirus pandemic (COVID-19). Thus, ACE2 is a potential target for drugs that disrupt the interaction of human cells with SARS-CoV-2 to abolish infection. There is also interest on drugs that inhibit or activate ACE2, i.e. for cardiovascular disorders or colitis. Compounds binding at alternative sites could allosterically affect the interaction with Spike protein. We here review biochemical, chemical biology and structural information on ACE2, including the recent cryoEM structures of full length ACE2. We conclude that ACE2 is very dynamic and that allosteric drugs may be developed to target ACE2. At the time of the 2020 pandemic, we suggest that available ACE2 inhibitors or activators in advanced development should be tested for their ability to allosterically displace the interaction between ACE2 and the Spike protein.

References

Oct 3, 2002·Journal of the American Chemical Society·Natalie A DalesMichael A Patane
Feb 28, 2003·The Journal of Biological Chemistry·Lili HuangRobert C Ladner
Dec 4, 2003·Biochemical and Biophysical Research Communications·Xiaodong XiaoDimiter S Dimitrov
Dec 13, 2003·The Journal of Biological Chemistry·Swee Kee WongMichael Farzan
Feb 3, 2004·The Journal of Biological Chemistry·Paul TowlerMichael W Pantoliano
Feb 26, 2004·Proceedings of the National Academy of Sciences of the United States of America·Jianhua SuiWayne A Marasco
May 29, 2004·Trends in Pharmacological Sciences·Anthony J TurnerNigel M Hooper
Oct 20, 2004·Hypertension·Matthew J HuentelmanDavid A Ostrov
Oct 22, 2004·Proceedings of the National Academy of Sciences of the United States of America·Scott A JeffersKathryn V Holmes
Nov 19, 2004·Cellular and Molecular Life Sciences : CMLS·F J WarnerA J Turner
Mar 26, 2005·The EMBO Journal·Wenhui LiMichael Farzan
May 18, 2005·Proceedings of the National Academy of Sciences of the United States of America·Heike HofmannStefan Pöhlmann
Mar 4, 2006·Circulation Research·Ursula Danilczyk, Josef M Penninger
Apr 28, 2007·The Journal of Pathology·I HammingH van Goor
Mar 8, 2008·Journal of Medicinal Chemistry·Andreas MoresVincent Dive
May 5, 2009·American Journal of Physiology. Lung Cellular and Molecular Physiology·Hong Peng JiaPaul B McCray
Jun 12, 2009·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·John J ByrnesDominic Picarella
Feb 6, 2010·Circulation Journal : Official Journal of the Japanese Circulation Society·Yumiko ImaiJosef M Penninger
Aug 24, 2011·Journal of Biomolecular Screening·Lidia V Kulemina, David A Ostrov
Jan 10, 2012·Annual Review of Biophysics·Jean-Pierre Changeux
Mar 5, 2013·Annual Review of Biophysics·Ruth NussinovBuyong Ma
Aug 22, 2013·Microbes and Infection·Thomas Perlot, Josef M Penninger
Dec 3, 2014·Journal of Hepatology·Tania Mara WelzelStefan Zeuzem
Sep 8, 2017·Critical Care : the Official Journal of the Critical Care Forum·Akram KhanAili L Lazaar
Jan 20, 2018·Physiological Reviews·Robson Augusto Souza SantosMaria Jose Campagnole-Santos
Mar 24, 2018·American Journal of Respiratory and Critical Care Medicine·Jiao ZhangJohn Y-J Shyy
May 3, 2018·Trends in Pharmacological Sciences·Erwin Sigel, Margot Ernst

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Citations

Jan 14, 2021·Cell Chemical Biology·Ruth NussinovVadim Gaponenko
Nov 17, 2020·Frontiers in Molecular Biosciences·Federica SaponaroRiccardo Zucchi
Feb 24, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Irma SaulleMara Biasin
Mar 27, 2021·Environmental Microbiology·Ruibang LuoAntoine Danchin
May 18, 2021·The Journal of Physical Chemistry Letters·Apurba BhattaraiYinglong Miao

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