scholarly journals Inhibitory efficiency of potential drugs against SARS-CoV-2 by blocking human angiotensin converting enzyme-2: Virtual screening and molecular dynamics study

2021 ◽  
Vol 152 ◽  
pp. 104762
Author(s):  
Abdul Ashik Khan ◽  
Nabajyoti Baildya ◽  
Tanmoy Dutta ◽  
Narendra Nath Ghosh
Keyword(s):  
Molecular Dynamics ◽  
Virtual Screening ◽  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Inhibitory Efficiency

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 Computational analysis on the ACE2-derived peptides for neutralizing the ACE2 binding to the spike protein of SARS-CoV-2

2020 ◽  
Author(s):  
Cecylia S. Lupala ◽  
Vikash Kumar ◽  
Xuanxuan Li ◽  
Xiao-dong Su ◽  
Haiguang Liu
Keyword(s):  
Molecular Dynamics ◽  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Computational Analysis ◽  
Spike Protein ◽  
Short Peptides ◽  
Receptor Binding Domain ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Dynamics Simulations

ABSTRACTThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19, is spreading globally and has infected more than 3 million people. It has been discovered that SARS-CoV-2 initiates the entry into cells by binding to human angiotensin-converting enzyme 2 (hACE2) through the receptor binding domain (RBD) of its spike glycoprotein. Hence, drugs that can interfere the SARS-CoV-2-RBD binding to hACE2 potentially can inhibit SARS-CoV-2 from entering human cells. Here, based on the N-terminal helix α1 of human ACE2, we designed nine short peptides that have potential to inhibit SARS-CoV-2 binding. Molecular dynamics simulations of peptides in the their free and SARS-CoV-2 RBD-bound forms allow us to identify fragments that are stable in water and have strong binding affinity to the SARS-CoV-2 spike proteins. The important interactions between peptides and RBD are highlighted to provide guidance for the design of peptidomimetics against the SARS-CoV-2.

scholarly journals Molecular Dynamics Simulation Study of the Interaction between Human Angiotensin Converting Enzyme 2 and Spike Protein Receptor Binding Domain of the SARS-CoV-2 B.1.617 Variant

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1244
Author(s):  
Priya Antony ◽  
Ranjit Vijayan
Keyword(s):  
Molecular Dynamics ◽  
Angiotensin Converting Enzyme ◽  
Molecular Dynamics Simulations ◽  
Receptor Binding ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Converting Enzyme ◽  
S Protein ◽  
Angiotensin Converting Enzyme 2 ◽  
Dynamics Simulations

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has had a significant impact on people’s daily lives. The rapidly spreading B.1.617 lineage harbors two key mutations—L452R and E484Q—in the receptor binding domain (RBD) of its spike (S) protein. To understand the impact and structural dynamics of the variations in the interface of S protein and its host factor, the human angiotensin-converting enzyme 2 (hACE2), triplicate 500 ns molecular dynamics simulations were performed using single (E484Q or L452R) and double (E484Q + L452R) mutant structures and compared to wild type simulations. Our results indicate that the E484Q mutation disrupts the conserved salt bridge formed between Lys31 of hACE2 and Glu484 of S protein. Additionally, E484Q, which could favor the up conformation of the RBD, may help in enhanced hACE2 binding and immune escape. L452R introduces a charged patch near the binding surface that permits increased electrostatic attraction between the proteins. An improved network of intramolecular interactions observed is likely to increase the stability of the S protein and conformational changes may prevent the binding of neutralizing antibodies. The results obtained from the molecular dynamics simulations suggest that structural and dynamic changes introduced by these variations enhance the affinity of the viral S protein to hACE2 and could form the basis for further studies.

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 ACE2 fragment as a decoy for novel SARS-Cov-2 virus

2020 ◽  
Author(s):  
Fabiana Renzi ◽  
Dario Ghersi
Keyword(s):  
Molecular Dynamics ◽  
Angiotensin Converting Enzyme ◽  
Molecular Dynamics Simulations ◽  
Cellular Membrane ◽  
Converting Enzyme ◽  
S Protein ◽  
Angiotensin Converting Enzyme 2 ◽  
Viral Binding ◽  
Binding Surface ◽  
Dynamics Simulations

Novel SARS-Cov-2 enters human cells via interaction between the surface spike (S) glycoprotein and the cellular membrane receptor angiotensin-converting enzyme 2 (ACE2). Using a combination of comparative structural analyses of the binding surface of the S protein to ACE2, docking experiments, and molecular dynamics simulations we computationally identified a minimal, stable fragment of ACE2. This fragment binds to the S protein, is soluble, and appears not to bind to the physiological ligand angiotensinII. These results suggest a possible use of the ACE2 fragment as a decoy that could interfere with viral binding by competition.

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