Cargando…
Diminazene Aceturate Reduces Angiotensin II Constriction and Interacts with the Spike Protein of Severe Acute Respiratory Syndrome Coronavirus 2
Diminazene aceturate (DIZE) is a putative angiotensin-converting enzyme 2 (ACE2) activator and angiotensin type 1 receptor antagonist (AT(1)R). Its simple chemical structure possesses a negatively charged triazene segment that is homologous to the tetrazole of angiotensin receptor blockers (ARB), wh...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9312513/ https://www.ncbi.nlm.nih.gov/pubmed/35885036 http://dx.doi.org/10.3390/biomedicines10071731 |
_version_ | 1784753860806443008 |
---|---|
author | Matsoukas, John M. Gadanec, Laura Kate Zulli, Anthony Apostolopoulos, Vasso Kelaidonis, Konstantinos Ligielli, Irene Moschovou, Kalliopi Georgiou, Nikitas Plotas, Panagiotis Chasapis, Christos T. Moore, Graham Ridgway, Harry Mavromoustakos, Thomas |
author_facet | Matsoukas, John M. Gadanec, Laura Kate Zulli, Anthony Apostolopoulos, Vasso Kelaidonis, Konstantinos Ligielli, Irene Moschovou, Kalliopi Georgiou, Nikitas Plotas, Panagiotis Chasapis, Christos T. Moore, Graham Ridgway, Harry Mavromoustakos, Thomas |
author_sort | Matsoukas, John M. |
collection | PubMed |
description | Diminazene aceturate (DIZE) is a putative angiotensin-converting enzyme 2 (ACE2) activator and angiotensin type 1 receptor antagonist (AT(1)R). Its simple chemical structure possesses a negatively charged triazene segment that is homologous to the tetrazole of angiotensin receptor blockers (ARB), which explains its AT(1)R antagonistic activity. Additionally, the activation of ACE2 by DIZE converts the toxic octapeptide angiotensin II (AngII) to the heptapeptides angiotensin 1–7 and alamandine, which promote vasodilation and maintains homeostatic balance. Due to DIZE’s protective cardiovascular and pulmonary effects and its ability to target ACE2 (the predominant receptor utilized by severe acute respiratory syndrome coronavirus 2 to enter host cells), it is a promising treatment for coronavirus 2019 (COVID-19). To determine DIZE’s ability to inhibit AngII constriction, in vitro isometric tension analysis was conducted on rabbit iliac arteries incubated with DIZE or candesartan and constricted with cumulative doses of AngII. In silico docking and ligand interaction studies were performed to investigate potential interactions between DIZE and other ARBs with AT(1)R and the spike protein/ACE2 complex. DIZE, similar to the other ARBs investigated, was able to abolish vasoconstriction in response to AngII and exhibited a binding affinity for the spike protein/ACE2 complex (PDB 6LZ6). These results support the potential of DIZE as a treatment for COVID-19. |
format | Online Article Text |
id | pubmed-9312513 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-93125132022-07-26 Diminazene Aceturate Reduces Angiotensin II Constriction and Interacts with the Spike Protein of Severe Acute Respiratory Syndrome Coronavirus 2 Matsoukas, John M. Gadanec, Laura Kate Zulli, Anthony Apostolopoulos, Vasso Kelaidonis, Konstantinos Ligielli, Irene Moschovou, Kalliopi Georgiou, Nikitas Plotas, Panagiotis Chasapis, Christos T. Moore, Graham Ridgway, Harry Mavromoustakos, Thomas Biomedicines Article Diminazene aceturate (DIZE) is a putative angiotensin-converting enzyme 2 (ACE2) activator and angiotensin type 1 receptor antagonist (AT(1)R). Its simple chemical structure possesses a negatively charged triazene segment that is homologous to the tetrazole of angiotensin receptor blockers (ARB), which explains its AT(1)R antagonistic activity. Additionally, the activation of ACE2 by DIZE converts the toxic octapeptide angiotensin II (AngII) to the heptapeptides angiotensin 1–7 and alamandine, which promote vasodilation and maintains homeostatic balance. Due to DIZE’s protective cardiovascular and pulmonary effects and its ability to target ACE2 (the predominant receptor utilized by severe acute respiratory syndrome coronavirus 2 to enter host cells), it is a promising treatment for coronavirus 2019 (COVID-19). To determine DIZE’s ability to inhibit AngII constriction, in vitro isometric tension analysis was conducted on rabbit iliac arteries incubated with DIZE or candesartan and constricted with cumulative doses of AngII. In silico docking and ligand interaction studies were performed to investigate potential interactions between DIZE and other ARBs with AT(1)R and the spike protein/ACE2 complex. DIZE, similar to the other ARBs investigated, was able to abolish vasoconstriction in response to AngII and exhibited a binding affinity for the spike protein/ACE2 complex (PDB 6LZ6). These results support the potential of DIZE as a treatment for COVID-19. MDPI 2022-07-18 /pmc/articles/PMC9312513/ /pubmed/35885036 http://dx.doi.org/10.3390/biomedicines10071731 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Matsoukas, John M. Gadanec, Laura Kate Zulli, Anthony Apostolopoulos, Vasso Kelaidonis, Konstantinos Ligielli, Irene Moschovou, Kalliopi Georgiou, Nikitas Plotas, Panagiotis Chasapis, Christos T. Moore, Graham Ridgway, Harry Mavromoustakos, Thomas Diminazene Aceturate Reduces Angiotensin II Constriction and Interacts with the Spike Protein of Severe Acute Respiratory Syndrome Coronavirus 2 |
title | Diminazene Aceturate Reduces Angiotensin II Constriction and Interacts with the Spike Protein of Severe Acute Respiratory Syndrome Coronavirus 2 |
title_full | Diminazene Aceturate Reduces Angiotensin II Constriction and Interacts with the Spike Protein of Severe Acute Respiratory Syndrome Coronavirus 2 |
title_fullStr | Diminazene Aceturate Reduces Angiotensin II Constriction and Interacts with the Spike Protein of Severe Acute Respiratory Syndrome Coronavirus 2 |
title_full_unstemmed | Diminazene Aceturate Reduces Angiotensin II Constriction and Interacts with the Spike Protein of Severe Acute Respiratory Syndrome Coronavirus 2 |
title_short | Diminazene Aceturate Reduces Angiotensin II Constriction and Interacts with the Spike Protein of Severe Acute Respiratory Syndrome Coronavirus 2 |
title_sort | diminazene aceturate reduces angiotensin ii constriction and interacts with the spike protein of severe acute respiratory syndrome coronavirus 2 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9312513/ https://www.ncbi.nlm.nih.gov/pubmed/35885036 http://dx.doi.org/10.3390/biomedicines10071731 |
work_keys_str_mv | AT matsoukasjohnm diminazeneaceturatereducesangiotensiniiconstrictionandinteractswiththespikeproteinofsevereacuterespiratorysyndromecoronavirus2 AT gadaneclaurakate diminazeneaceturatereducesangiotensiniiconstrictionandinteractswiththespikeproteinofsevereacuterespiratorysyndromecoronavirus2 AT zullianthony diminazeneaceturatereducesangiotensiniiconstrictionandinteractswiththespikeproteinofsevereacuterespiratorysyndromecoronavirus2 AT apostolopoulosvasso diminazeneaceturatereducesangiotensiniiconstrictionandinteractswiththespikeproteinofsevereacuterespiratorysyndromecoronavirus2 AT kelaidoniskonstantinos diminazeneaceturatereducesangiotensiniiconstrictionandinteractswiththespikeproteinofsevereacuterespiratorysyndromecoronavirus2 AT ligielliirene diminazeneaceturatereducesangiotensiniiconstrictionandinteractswiththespikeproteinofsevereacuterespiratorysyndromecoronavirus2 AT moschovoukalliopi diminazeneaceturatereducesangiotensiniiconstrictionandinteractswiththespikeproteinofsevereacuterespiratorysyndromecoronavirus2 AT georgiounikitas diminazeneaceturatereducesangiotensiniiconstrictionandinteractswiththespikeproteinofsevereacuterespiratorysyndromecoronavirus2 AT plotaspanagiotis diminazeneaceturatereducesangiotensiniiconstrictionandinteractswiththespikeproteinofsevereacuterespiratorysyndromecoronavirus2 AT chasapischristost diminazeneaceturatereducesangiotensiniiconstrictionandinteractswiththespikeproteinofsevereacuterespiratorysyndromecoronavirus2 AT mooregraham diminazeneaceturatereducesangiotensiniiconstrictionandinteractswiththespikeproteinofsevereacuterespiratorysyndromecoronavirus2 AT ridgwayharry diminazeneaceturatereducesangiotensiniiconstrictionandinteractswiththespikeproteinofsevereacuterespiratorysyndromecoronavirus2 AT mavromoustakosthomas diminazeneaceturatereducesangiotensiniiconstrictionandinteractswiththespikeproteinofsevereacuterespiratorysyndromecoronavirus2 |