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 (AT1R). Its simple chemical structure possesses a negatively charged triazene segment that is homologous to the tetrazole of angiotensin receptor blockers (ARB), whic...

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Published in:Biomedicines 2022-07, Vol.10 (7), p.1731
Main Authors: 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
Format: Article
Language:English
Subjects:
ACE2
Angiotensin
Angiotensin II
angiotensin type 1 receptor
Angiotensin-converting enzyme 2
Animals
Arteries
Blood pressure
coronavirus 2019
Coronaviruses
COVID-19
diminazene aceturate
Disease transmission
Enzymes
FDA approval
Hypertension
Infections
Isometric
Nitric oxide
Peptidyl-dipeptidase A
Proteins
sartans
Severe acute respiratory syndrome coronavirus 2
Spike protein
Vasoconstriction
Vasodilation
Viral infections
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Summary:Diminazene aceturate (DIZE) is a putative angiotensin-converting enzyme 2 (ACE2) activator and angiotensin type 1 receptor antagonist (AT1R). Its simple chemical structure possesses a negatively charged triazene segment that is homologous to the tetrazole of angiotensin receptor blockers (ARB), which explains its AT1R 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 AT1R 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.
ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines10071731