In Silico Exploration of Potential Natural Inhibitors against SARS-Cov-2 nsp10

In continuation of our previous effort, different in silico selection methods were applied to 310 naturally isolated metabolites that exhibited antiviral potentialities before. The applied selection methods aimed to pick the most relevant inhibitor of SARS-CoV-2 nsp10. At first, a structural similarity study against the co-crystallized ligand, S-Adenosyl Methionine (SAM), of SARS-CoV-2 nonstructural protein (nsp10) (PDB ID: 6W4H) was carried out. The similarity analysis culled 30 candidates. Secondly, a fingerprint study against SAM preferred compounds 44, 48, 85, 102, 105, 182, 220, 221, 282, 284, 285, 301, and 302. The docking studies picked 48, 182, 220, 221, and 284. While the ADMET analysis expected the likeness of the five candidates to be drugs, the toxicity study preferred compounds 48 and 182. Finally, a density-functional theory (DFT) study suggested vidarabine (182) to be the most relevant SARS-Cov-2 nsp10 inhibitor.

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In silico Discovery of Resveratrol Analogues as Potential Agents in Treatment of Metabolic Disorders

Current Pharmaceutical Design ◽

10.2174/1381612825666191029095252 ◽

2019 ◽

Vol 25 (35) ◽

pp. 3776-3783

Author(s):

Nebojša Pavlović ◽

Maja Đanić ◽

Bojan Stanimirov ◽

Svetlana Goločorbin-Kon ◽

Karmen Stankov ◽

...

Keyword(s):

In Silico ◽

Metabolic Disorders ◽

Partial Agonist ◽

Aqueous Solubility ◽

Structural Similarity ◽

Data Bank ◽

Docking Studies ◽

Binding Energies ◽

Molegro Virtual Docker ◽

Ppar Γ

Background: Resveratrol was demonstrated to act as partial agonist of PPAR-γ receptor, which opens up the possibility for its use in the treatment of metabolic disorders. Considering the poor bioavailability of resveratrol, particularly due to its low aqueous solubility, we aimed to identify analogues of resveratrol with improved pharmacokinetic properties and higher binding affinities towards PPAR-γ. Methods: 3D structures of resveratrol and its analogues were retrieved from ZINC database, while PPAR-γ structure was obtained from Protein Data Bank. Docking studies were performed using Molegro Virtual Docker software. Molecular descriptors relevant to pharmacokinetics were calculated from ligand structures using VolSurf+ software. Results: Using structural similarity search method, 56 analogues of resveratrol were identified and subjected to docking analyses. Binding energies were ranged from -136.69 to -90.89 kcal/mol, with 16 analogues having higher affinities towards PPAR-γ in comparison to resveratrol. From the calculated values of SOLY descriptor, 23 studied compounds were shown to be more soluble in water than resveratrol. However, only two tetrahydroxy stilbene derivatives, piceatannol and oxyresveratrol, had both better solubility and affinity towards PPAR-γ. These compounds also had more favorable ADME profile, since they were shown to be more metabolically stable and wider distributed in body than resveratrol. Conclusion: Piceatannol and oxyresveratrol should be considered as potential lead compounds for further drug development. Although experimental validation of obtained in silico results is required, this work can be considered as a step toward the discovery of new natural and safe drugs in treatment of metabolic disorders.

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Molecular docking and density functional theory studies on creatine, guanidinoacetic acid, and their phosphorylated analogues binding to muscle creatine kinase

Journal of Chemical Research ◽

10.1177/1747519820978583 ◽

2020 ◽

pp. 174751982097858

Author(s):

M Vraneš ◽

S Ostojić ◽

Č Podlipnik ◽

A Tot

Keyword(s):

Density Functional Theory ◽

Creatine Kinase ◽

Molecular Docking ◽

Density Functional ◽

Creatine Phosphate ◽

Docking Studies ◽

Muscle Creatine Kinase ◽

Functional Theory ◽

Guanidinoacetic Acid ◽

Muscle Creatine

Comparative molecular docking studies on creatine and guanidinoacetic acid, as well as their phosphorylated analogues, creatine phosphate, and phosphorylated guanidinoacetic acid, are investigated. Docking and density functional theory studies are carried out for muscle creatine kinase. The changes in the geometries of the ligands before and after binding to the enzyme are investigated to explain the better binding of guanidinoacetic acid and phosphorylated guanidinoacetic acid compared to creatine and creatine phosphate.

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Synthesis and DPPH scavenging assay of reserpine analogues, computational studies and in silico docking studies in AChE and BChE responsible for Alzheimer's disease

Brazilian Journal of Pharmaceutical Sciences ◽

10.1590/s1984-82502015000100006 ◽

2015 ◽

Vol 51 (1) ◽

pp. 53-61 ◽

Cited By ~ 2

Author(s):

Muhammad Yar ◽

Muhammad Arshad ◽

Ariba Farooq ◽

Mazhar Amjad Gilani ◽

Khurshid Ayub ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Free Radicals ◽

In Silico ◽

Density Functional ◽

Neurodegenerative Disorder ◽

Antioxidant Properties ◽

Docking Studies ◽

In Silico Docking ◽

Ic50 Values

Alzheimer's disease (AD) is a fast growing neurodegenerative disorder of the central nervous system and anti-oxidants can be used to help suppress the oxidative stress caused by the free radicals that are responsible for AD. A series of selected synthetic indole derivatives were biologically evaluated to identify potent new antioxidants. Most of the evaluated compounds showed significant to modest antioxidant properties (IC50 value 399.07 140.0±50 µM). Density Functional Theory (DFT) studies were carried out on the compounds and their corresponding free radicals. Differences in the energy of the parent compounds and their corresponding free radicals provided a good justification for the trend found in their IC50 values. In silico, docking of compounds into the proteins acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), which are well known for contributing in AD disease, was also performed to predict anti-AD potential.

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Synthesis, structural, spectroscopic and docking studies on (E)-1-Ferrocenyl-3-phenylpropen-1-one by the density functional theory

Molecular Simulation ◽

10.1080/08927022.2021.2016743 ◽

2021 ◽

pp. 1-16

Author(s):

M. Amalanathan ◽

M. Sony Michael Mary ◽

M. Latha Beatrice ◽

S. Mary Delphine ◽

H. Marshan Robert ◽

...

Keyword(s):

Density Functional Theory ◽

Density Functional ◽

Docking Studies ◽

Functional Theory ◽

The Density Functional Theory

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Synthesis, crystal structure, photophysical properties, density functional theory calculations and molecular docking studies on Cd(II) complex of 4,4′-dimethyl-2,2′-dipyridyl

Journal of Molecular Structure ◽

10.1016/j.molstruc.2019.127288 ◽

2020 ◽

Vol 1202 ◽

pp. 127288 ◽

Cited By ~ 2

Author(s):

Ömer Tamer ◽

Davut Avcı ◽

Necmi Dege ◽

Yusuf Atalay

Keyword(s):

Crystal Structure ◽

Density Functional Theory ◽

Molecular Docking ◽

Density Functional ◽

Photophysical Properties ◽

Density Functional Theory Calculations ◽

Docking Studies ◽

Functional Theory ◽

Molecular Docking Studies

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In Silico Modeling of Spirolides and Gymnodimines: Determination of S Configuration at Butenolide Ring Carbon C-4

Toxins ◽

10.3390/toxins12110685 ◽

2020 ◽

Vol 12 (11) ◽

pp. 685

Author(s):

Christian Zurhelle ◽

Tilmann Harder ◽

Urban Tillmann ◽

Jan Tebben

Keyword(s):

In Silico ◽

Density Functional ◽

Nuclear Overhauser Effect ◽

Resonance Spectroscopy ◽

Functional Theory ◽

Relative Configuration ◽

Overhauser Effect ◽

In Silico Modeling ◽

Nuclear Overhauser

Only few naturally occurring cyclic imines have been fully structurally elucidated or synthesized to date. The configuration at the C-4 carbon plays a pivotal role in the neurotoxicity of many of these metabolites, for example, gymnodomines (GYMs) and spirolides (SPXs). However, the stereochemistry at this position is not accessible by nuclear Overhauser effect—nuclear magnetic resonance spectroscopy (NOE-NMR) due to unconstrained rotation of the single carbon bond between C-4 and C-5. Consequently, the relative configuration of GYMs and SPXs at C-4 and its role in protein binding remains elusive. Here, we determined the stereochemical configuration at carbon C-4 in the butenolide ring of spirolide- and gymnodimine-phycotoxins by comparison of measured 13C NMR shifts with values obtained in silico using force field, semiempirical and density functional theory methods. This comparison demonstrated that modeled data support S configuration at C-4 for all studied SPXs and GYMs, suggesting a biosynthetically conserved relative configuration at carbon C-4 among these toxins.

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