Antiviral potential of diminazene aceturate against SARS-CoV-2 proteases using computational and in vitro approaches

Antiviral potential of diminazene aceturate against SARS-CoV-2 proteases using computational and in vitro approaches

Diminazene aceturate (DIZE), an antiparasitic, is an ACE2 activator, and studies show that activators of this enzyme may be beneficial for COVID-19, disease caused by SARS-CoV-2. Thus, the objective was to evaluate the in silico and in vitro affinity of diminazene aceturate against molecular targets...

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Bibliographic Details
Published in:Chemico-biological interactions Vol. 367; p. 110161
Main Authors: Santos, Esley S., Silva, Priscila C., Sousa, Paulo S.A., Aquino, Cristhyane C., Pacheco, Gabriella, Teixeira, Luiz F.L.S., Araujo, Alyne R., Sousa, Francisca B.M., Barros, Romulo O., Ramos, Ricardo M., Rocha, Jefferson A., Nicolau, Lucas A.D., Medeiros, Jand V.R.
Format: Journal Article
Language:English
Published: Ireland Elsevier B.V 01-11-2022
Subjects:
Angiotensin-Converting Enzyme 2
Antiparasitic Agents
Antiviral Agents - chemistry
Antiviral Agents - pharmacology
COVID-19
COVID-19 Drug Treatment
Diminazene - analogs & derivatives
Diminazene aceturate
Humans
Molecular Docking Simulation
Peptide Hydrolases
Peptidyl-Dipeptidase A - chemistry
Protein S
Research Paper
SARS-CoV-2
Diminazene aceturate
COVID-19
SARS-CoV-2
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Summary:Diminazene aceturate (DIZE), an antiparasitic, is an ACE2 activator, and studies show that activators of this enzyme may be beneficial for COVID-19, disease caused by SARS-CoV-2. Thus, the objective was to evaluate the in silico and in vitro affinity of diminazene aceturate against molecular targets of SARS-CoV-2. 3D structures from DIZE and the proteases from SARS-CoV-2, obtained through the Protein Data Bank and Drug Database (Drubank), and processed in computer programs like AutodockTools, LigPlot, Pymol for molecular docking and visualization and GROMACS was used to perform molecular dynamics. The results demonstrate that DIZE could interact with all tested targets, and the best binding energies were obtained from the interaction of Protein S (closed conformation −7.87 kcal/mol) and Mpro (−6.23 kcal/mol), indicating that it can act both by preventing entry and viral replication. The results of molecular dynamics demonstrate that DIZE was able to promote a change in stability at the cleavage sites between S1 and S2, which could prevent binding to ACE2 and fusion with the membrane. In addition, in vitro tests confirm the in silico results showing that DIZE could inhibit the binding between the spike receptor-binding domain protein and ACE2, which could promote a reduction in the virus infection. However, tests in other experimental models with in vivo approaches are needed. [Display omitted] •Treatment of patients using ACE2 activators could bring two therapeutic benefits.•DIZE has the potential to promote the reduction of infection by SARS-CoV-2.•We hypothesize that it may have promising therapeutic effects against COVID-19.•Binding of DIZE to S-RBD protein residues reduces the interaction with ACE2.
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ISSN:0009-2797
1872-7786
DOI:10.1016/j.cbi.2022.110161