Structure-Based Pharmacophore Design and Virtual Screening for Novel Angiotensin Converting Enzyme 2 Inhibitors

2006 ◽  
Vol 46 (2) ◽  
pp. 708-716 ◽  
Author(s):  
Monika Rella ◽  
Christopher A. Rushworth ◽  
Jodie L. Guy ◽  
Anthony J. Turner ◽  
Thierry Langer ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2

scholarly journals Virtual screening as therapeutic strategy of COVID-19 targeting angiotensin-converting enzyme 2

2021 ◽  
Vol 2 (1) ◽  
pp. 16-27
Author(s):  
Zahra Sharifinia ◽  
◽  
Samira Asadi ◽  
Mahyar Irani ◽  
Abdollah Allahverdi ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Angiotensin Converting Enzyme ◽  
Host Cells ◽  
Spike Protein ◽  
Potential Drug ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Approved Drugs ◽  
Fda Approved Drugs

Objective: The receptor-binding domain (RBD) of the S1 domain of the SARS-CoV- 2 Spike protein performs a key role in the interaction with Angiotensin-converting enzyme 2 (ACE2), leading to both subsequent S2 domain-mediated membrane fusion and incorporation of viral RNA in host cells. Methods: In this study, we investigated the inhibitor’s targeted compounds through existing human ACE2 drugs to use as a future viral invasion. 54 FDA approved drugs were selected to assess their binding affinity to the ACE2 receptor. The structurebased methods via computational ones have been used for virtual screening of the best drugs from the drug database. Key Findings: The ligands “Cinacalcet” and “Levomefolic acid” highaffinity scores can be a potential drug preventing Spike protein of SARS-CoV-2 and human ACE2 interaction. Levomefolic acid from vitamin B family was proved to be a potential drug as a spike protein inhibitor in previous clinical and computational studies. Besides that, in this study, the capability of Levomefolic acid to avoid ACE2 and Spike protein of SARS-CoV-2 interaction is indicated. Therefore, it is worth to consider this drug for more in vitro investigations as ACE2 and Spike protein inhibition candidate. Conclusion: The two Cinacalcet and Levomefolic acid are the two ligands that have highest energy binding for human ACE2 blocking among 54 FDA approved drugs.

scholarly journals Virtual Screening in Search for a Chemical Probe for Angiotensin-Converting Enzyme 2 (ACE2)

Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7584
Author(s):  
Iryna O. Kravets ◽  
Dmytro V. Dudenko ◽  
Alexander E. Pashenko ◽  
Tatiana A. Borisova ◽  
Ganna M. Tolstanova ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Angiotensin Converting Enzyme ◽  
Cost Effective ◽  
Converting Enzyme ◽  
Chemical Probes ◽  
Angiotensin Converting Enzyme 2 ◽  
Cpu Time ◽  
New Models ◽  
The Cost

We elaborate new models for ACE and ACE2 receptors with an excellent prediction power compared to previous models. We propose promising workflows for working with huge compound collections, thereby enabling us to discover optimized protocols for virtual screening management. The efficacy of elaborated roadmaps is demonstrated through the cost-effective molecular docking of 1.4 billion compounds. Savings of up to 10-fold in CPU time are demonstrated. These developments allowed us to evaluate ACE2/ACE selectivity in silico, which is a crucial checkpoint for developing chemical probes for ACE2.

scholarly journals Discovery of a potent angiotensin converting enzyme 2 inhibitor from Chinese Medicinal and Edible Plant via Docking-based Virtual Screening

2020 ◽  
Author(s):  
Cheng-Ting Zi ◽  
Ning Zhang ◽  
Liu Yang ◽  
Li-Xia Wang ◽  
Yi-Long Wu ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Angiotensin Converting Enzyme ◽  
Acid Methyl Ester ◽  
Antiviral Drugs ◽  
Converting Enzyme ◽  
Edible Plant ◽  
Angiotensin Converting Enzyme 2 ◽  
Lead Compounds ◽  
Promising Target

Abstract COVID-19 has outbreaked in Wuhan city, Hubei province of China since December 30th 2019, and spread nationwide and widely spilled over to other countries around the world that has been declared a public health emergency. However, there is no specific drug for the treatment of the disease. Therefore, identifying effective antiviral drugs to combat the disease is urgently needed. Angiotensin converting enzyme 2 (ACE2) has become the promising target to discovery new antiviral drugs to treat COVID-19, we have attempted to discover novel ACE2 inhibitors through ligand-based virtual screening. Finally, eight compounds were selected and tested ACE2 kinase inhibitory assay using fluorescence assays method. The results showed that four compounds (monoammonium glycyrrhizinate, glycyrrhizic acid methyl ester, ginsenoside Rg6 and ginsenoside F1) from 101 kinds of Chinese medicinal and edible plants which could inhibit ACE2 activity in vitro. Further efforts on chemical modification of these lead compounds are undergoing can lead to discover better agents against COVID-19.

Thermodynamics of the interaction between the spike protein of severe acute respiratory syndrome- coronavirus-2 and the receptor of human angiotensin converting enzyme 2. Effects of possible ligands

2020 ◽  
Author(s):  
Cristina Garcia-Iriepa ◽  
Cecilia Hognon ◽  
Antonio Francés-Monerris ◽  
Isabel Iriepa ◽  
Tom Miclot ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Molecular Mechanisms ◽  
Molecular Design ◽  
Binding Free Energy ◽  
Transmembrane Protein ◽  
Spike Protein ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Rational Molecular Design ◽  
Rational Evaluation

<div><p>Since the end of 2019, the coronavirus SARS-CoV-2 has caused more than 180,000 deaths all over the world, still lacking a medical treatment despite the concerns of the whole scientific community. Human Angiotensin-Converting Enzyme 2 (ACE2) was recently recognized as the transmembrane protein serving as SARS-CoV-2 entry point into cells, thus constituting the first biomolecular event leading to COVID-19 disease. Here, by means of a state-of-the-art computational approach, we propose a rational evaluation of the molecular mechanisms behind the formation of the complex and of the effects of possible ligands. Moreover, binding free energy between ACE2 and the active Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein is evaluated quantitatively, assessing the molecular mechanisms at the basis of the recognition and the ligand-induced decreased affinity. These results boost the knowledge on the molecular grounds of the SARS-CoV-2 infection and allow to suggest rationales useful for the subsequent rational molecular design to treat severe COVID-19 cases.</p></div>

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