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

Autor: Mariana Sacerdoti, Lissy Zoe Florens Gross, Stefan Zeuzem, Ricardo M. Biondi, Albrecht Piiper, Alejandro E. Leroux
Jazyk: angličtina
Rok vydání: 2020
Předmět:
ACE2
Angiotensin-Converting Enzyme Inhibitors
Protein dynamics
Plasma protein binding
medicine.disease_cause
01 natural sciences
Biochemistry
purl.org/becyt/ford/1 [https]
Catalytic Domain
Drug Discovery
General Pharmacology
Toxicology and Pharmaceutics
Allostery
Receptor
Coronavirus
Allosteric drug development
Chemistry
purl.org/becyt/ford/3.1 [https]
Medicina Química
Bioquímica y Biología Molecular
PROTEIN-PROTEIN INTERACTION
Cell biology
Medicina Básica
Drug development
Spike Glycoprotein
Coronavirus
Receptors
Virus
Molecular Medicine
purl.org/becyt/ford/3 [https]
Angiotensin-Converting Enzyme 2
ALLOSTERY
CIENCIAS NATURALES Y EXACTAS
hormones
hormone substitutes
and hormone antagonists
Protein Binding
CIENCIAS MÉDICAS Y DE LA SALUD
Protein domain
Allosteric regulation
Chemical biology
Peptidyl-Dipeptidase A
Protein–protein interaction
Ciencias Biológicas
Betacoronavirus
Allosteric Regulation
Protein Domains
medicine
Humans
purl.org/becyt/ford/1.6 [https]
DRUG DEVELOPMENT
Pharmacology
SARS-CoV-2
010405 organic chemistry
Organic Chemistry
COVID-19
Biofísica
0104 chemical sciences
010404 medicinal & biomolecular chemistry
Minireview
Zdroj: ChemMedChem
CONICET Digital (CONICET)
Consejo Nacional de Investigaciones Científicas y Técnicas
instacron:CONICET
Chemmedchem
ISSN: 1860-7187
1860-7179
DOI: 10.1002/cmdc.202000368
Popis: 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. Fil: Gross, Lissy Zoe Florens. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina Fil: Sacerdoti, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina Fil: Piiper, Albrecht. Goethe Universitat Frankfurt; Alemania Fil: Zeuzem, Stefan. Goethe Universitat Frankfurt; Alemania Fil: Leroux, Alejandro Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina Fil: Biondi, Ricardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
Databáze: OpenAIRE
Externí odkaz: