scholarly journals Allergen fragrance molecules: a potential relief for COVID-19

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Aslı Deniz Aydın ◽  
Faruk Altınel ◽  
Hüseyin Erdoğmuş ◽  
Çağdaş Devrim Son
Keyword(s):  
Binding Affinity ◽  
Docking Studies ◽  
Binding Energies ◽  
Binding Affinities ◽  
Flexible Docking ◽  
Potential Relief ◽  
Docking Simulations ◽  
Molegro Virtual Docker ◽  
Drug Molecules ◽  
Docking Protocol

Abstract Background The latest coronavirus SARS-CoV-2, discovered in China and rapidly spread Worldwide. COVID-19 affected millions of people and killed hundreds of thousands worldwide. There are many ongoing studies investigating drug(s) suitable for preventing and/or treating this pandemic; however, there are no specific drugs or vaccines available to treat or prevent SARS-CoV-2 as of today. Methods Fifty-eight fragrance materials, which are classified as allergen fragrance molecules, were selected and used in this study. Docking simulations were carried out using four functional proteins; the Covid19 Main Protase (MPro), Receptor binding domain (RBD) of spike protein, Nucleocapsid, and host Bromodomain protein (BRD2), as target macromolecules. Three different software, AutoDock, AutoDock Vina (Vina), and Molegro Virtual Docker (MVD), running a total of four different docking protocol with optimized energy functions were used. Results were compared with the five molecules reported in the literature as potential drugs against COVID-19. Virtual screening was carried out using Vina, molecules satisfying our cut-off (− 6.5 kcal/mol) binding affinity was confirmed by MVD. Selected molecules were analyzed using the flexible docking protocol of Vina and AutoDock default settings. Results Ten out of 58 allergen fragrance molecules were selected for further docking studies. MPro and BRD2 are potential targets for the tested allergen fragrance molecules, while RBD and Nucleocapsid showed weak binding energies. According to AutoDock results, three molecules, Benzyl Cinnamate, Dihydroambrettolide, and Galaxolide, had good binding affinities to BRD2. While Dihydroambrettolide and Galaxolide showed the potential to bind to MPro, Sclareol and Vertofix had the best calculated binding affinities to this target. When the flexible docking results analyzed, all the molecules tested had better calculated binding affinities as expected. Benzyl Benzoate and Benzyl Salicylate showed good binding affinities to BRD2. In the case of MPro, Sclareol had the lowest binding affinity among all the tested allergen fragrance molecules. Conclusion Allergen fragrance molecules are readily available, cost-efficient, and shown to be safe for human use. Results showed that several of these molecules had comparable binding affinities as the potential drug molecules reported in the literature to target proteins. Thus, these allergen molecules at correct doses could have significant health benefits.

scholarly journals Allergen Fragrance Molecules: A Potential Relief for COVID-19

2020 ◽  
Author(s):  
Aslı Deniz Aydın ◽  
Faruk Altınel ◽  
Hüseyin Erdoğmuş ◽  
Cagdas Devrim Son
Keyword(s):  
Binding Affinity ◽  
Docking Studies ◽  
Binding Energies ◽  
Binding Affinities ◽  
Flexible Docking ◽  
Potential Relief ◽  
Docking Simulations ◽  
Molegro Virtual Docker ◽  
Drug Molecules ◽  
Docking Protocol

Abstract Background: The latest coronavirus SARS-CoV-2, discovered in China and rapidly spread Worldwide. COVID-19 affected millions of people and killed hundreds of thousands worldwide. There are many ongoing studies investigating drug(s) suitable for preventing and/or treating this pandemic; however, there are no specific drugs or vaccines available to treat or prevent SARS-CoV-2 as of today.Methods: 58 fragrance materials, which are classified as allergen fragrance molecules, were selected and used in this study. Docking simulations were carried out using four functional proteins; the Covid19 Main Protase (Mpro), Receptor binding domain (RBD) of spike protein, Nucleocapsid, and host Bromodomain protein (BRD2), as target macromolecules. Three different software, AutoDock, AutoDock Vina (Vina), and Molegro Virtual Docker (MVD), running a total of four different docking protocol with optimized energy functions were used. Results were compared with the five molecules reported in the literature as potential drugs against COVID-19. Virtual screening was carried out using Vina, molecules satisfying our cut-off (-6.5 kcal/mol) binding affinity was confirmed by MVD. Selected molecules were analyzed using the flexible docking protocol of Vina and AutoDock default settings. Results: Ten out of 58 allergen fragrance molecules were selected for further docking studies. Mpro and BRD2 are potential targets for the tested allergen fragrance molecules, while RBD and Nucleocapsid showed weak binding energies. According to AutoDock results, three molecules, Benzyl Cinnamate, Dihydroambrettolide, and Galaxolide, had good binding affinities to BRD2. While Dihydroambrettolide and Galaxolide showed the potential to bind to Mpro, Sclareol and Vertofix had the best calculated binding affinities to this target. When the flexible docking results analyzed, all the molecules tested had better calculated binding affinities as expected. Benzyl Benzoate and Benzyl Salicylate showed good binding affinities to BRD2. In the case of Mpro, Sclareol had the lowest binding affinity among all the tested allergen fragrance molecules. Conclusion: Allergen fragrance molecules are readily available, cost-efficient, and shown to be safe for human use. Results showed that several of these molecules had comparable binding affinities as the potential drug molecules reported in the literature to target proteins. Thus, these allergen molecules at correct doses could have significant health benefits.

In Silico Docking of Anti Cancerous Drugs with β-Cyclodextrin polymer as a Prominent Approach to Improve the Bioavailability

2020 ◽  
Vol 20 ◽  
Author(s):  
Akhlesh K. Jain ◽  
Keerti Mishra ◽  
Suresh Thareja
Keyword(s):  
Binding Affinity ◽  
Chemical Structure ◽  
Water Solubility ◽  
Binding Affinities ◽  
Pharmacological Profile ◽  
Bioavailability Enhancement ◽  
Docking Simulations ◽  
Molegro Virtual Docker ◽  
In Silico Docking ◽  
Integrated Software

Background: β-Cyclodextrin, a cyclic oligosaccharides having 7 macrocyclic ring of glucose sub units usually linked together by ɑ-1,4 glycosidic bond, bears characteristic chemical structure, with exterior portion as hydrophilic to impart water solubility and interior cavity as hydrophobic, for hosting the hydrophobic molecules. Objective: In the present work binding affinities and interactions between various anti-cancerous drugs and β-cyclodextrin using molecular docking simulations was examined for the bioavailability enhancement of cytotoxic drugs through improved solubility for the treatment of breast cancer. Methods: Molegro Virtual Docker, an integrated software was used for the prediction and estimation of interaction between βcyclodextrin and anti cancerous drugs. Results: Out of tested anti cancerous drug, Olaparib having pyridopyridazione scaffold possess highest MolDock (-130.045) and Reranks score (-100.717), ensuring strong binding affinity. However, 5-Fluoro Uracil exhibited lowest MolDock score (-61.0045), indicating weak or no binding affinity, while few drugs showed no H-bond interaction with the β-cyclodextrin. Conclusion: The binding conformations of anti cancerous drugs obtained from the present study can be selected for development of improved formulation having superior solubility which will lead to attain better pharmacological profile with negligible toxicity.

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

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.

scholarly journals Harnessing the Sars-cov-2 Spike Protein Binding Affinity to Ace2 Receptor Through Narcotinic Compounds Combined With Adjuvants: an in Silico Insight

2021 ◽  
Author(s):  
Saeedeh Mohammadi ◽  
Esmail Doustkhah ◽  
Nader Sakhaee ◽  
Ayoub Esmailpour ◽  
Mohammad Esmailpour
Keyword(s):  
Binding Affinity ◽  
In Silico ◽  
Muramyl Dipeptide ◽  
Docking Studies ◽  
Spike Protein ◽  
Binding Affinities ◽  
Narcotic Analgesics ◽  
S Protein ◽  
Suitable Combination ◽  
Spike Proteins

Abstract Protein products of SARS-CoV-2 spike (S) coding gene sequence, were all analyzed and compared to other SARS-CoV S proteins to elucidate structural similarities of spike proteins. A homology modeling of SARS-CoV-2 S protein was obtained and used in molecular docking studies to find binding affinities of spike protein for angiotensin-converting enzyme 2 (ACE2). The two most important binding sites of S protein, namely, RBD and CTD, critically responsible for binding interactions, were identified. Finally, binding affinity of RBD and CTD domains of S protein with narcotic analgesics are studied. Moreover, interactions of ACE2 receptor- S protein with narcotic compounds when mixed with small molecule adjuvants to improve the immune response and increase the efficacy of potential vaccines, were taken into consideration. In-silico results suggest that the combination of narcotine hemiacetal with mannide monooleate shows a stronger binding affinity with CTD, while carprofen-muramyl dipeptide and squalene have stronger binding affinities for the RBD portion of S protein. Thus, a suitable combination of these narcotic is proposed to yield potent site-blocking efficacy for ACE2 receptor against SARS-CoV-2 spike proteins.

scholarly journals Synthesis, Spectral Characterization and Molecular Docking Studies of Novel Benzidin-bis-tetrahydroacridine Analogues

2020 ◽  
Vol 71 (5) ◽  
pp. 163-181
Author(s):  
Madalina Marina Hrubaru ◽  
Carmellina Daniela Badiceanu ◽  
Anthony Chinonso Ekennia ◽  
Sunday N. Okafor ◽  
Cristian Enache ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Sites ◽  
Docking Studies ◽  
Binding Affinities ◽  
Binding Modes ◽  
Docking Simulations ◽  
Ft Ir ◽  
Dynamics Simulations ◽  
And Behavior ◽  
Human Butyrylcholinesterase

Alzheimer�s is a progresive neurodegenerative disease that interferes with human cognitive ability, memory and behavior. The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes are major therapeutic routes for the treatment of Alzheimer disease. In the study, nevel bis-polymethylenquinoline-bis-carboxamides (3a-f) and bis-polymethylenquinoline-bis-carboxylic acids (5a-b) having as precursor benzidine, were obtained in good yields by Pfitzinger condensation reactions of bis-isatines with corresponding cyclanones. The compounds were characterized by elemental analysis, FT-IR, NMR and mass spectrometry. Furthermore, the compounds were subjected to molecular docking dynamics simulations to ascertain their potentials as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Molecular docking simulations showed varied binding activities towards the two binding sites of acetylcholinesterase: 4EY7 and 1OCD, and human butyrylcholinesterase: 1P0I. Compounds 3e and 5b demostrated strong binding affinities with 1P0I, 1OCD and 4EY7 biotargets similar to the binding modes of donepezil and tacrine (co-crystallized inhibitors of acetylcholinesterase) and butyrate (co-crystallized inhibitors of butyrylcholinesterase).

Docking Investigation on Bis (Nitro Indazolyl) Methanes; Synthesis and Antimicrobial Activity Towards Breast Cancer Applications

2021 ◽  
Vol 18 ◽  
Author(s):  
S. Jagadeesan ◽  
S. Karpagam
Keyword(s):  
Breast Cancer ◽  
Antimicrobial Activity ◽  
Docking Studies ◽  
Klebsiella Pneumonia ◽  
Binding Affinities ◽  
Efficient Catalyst ◽  
Molegro Virtual Docker ◽  
Starting Point ◽  
Wide Range ◽  
Human Estrogen Receptor

: Bismuth (III) nitrate pentahydrate (BN) was found to be a mild and efficient catalyst for the electrophilic condensation of 5-nitroindazole with a wide range of aldehydes to obtain Bis (5-nitro indazolyl) methanes 3 (a-h) at ambient temperature. This was structurally confirmed from FTIR, NMR, and HR-MS technique. Molecular docking studies of all compounds was carried out using breast cancer-causing human estrogen receptor (ER) from Molegro Virtual Docker software. Hydroxy Bis (nitro indazolyl) methanes (3b) were shown better binding affinities and the score obtained was -150.146 Kcal/mol compared with Tamoxifen drug. The major H-bond interactions were observed with the compound 3f and the value was -5.679. The antimicrobial activity results revealed that compounds 3b and 3d showed promising activity against bacteria Escherichia coli, Klebsiella pneumonia, Staphylococcus aureus, and Pseudomonas aeruginosa and maximum inhibition against Aspergillus niger and Aspergillus flavus. Methoxy derivatives of Bis (nitro indazolyl methanes) (3e) have shown better antioxidant activity and low MIC (6.25 µg/ml) observed for the compounds 3a and 3b. The synthesized compounds have a very promising starting point for the development and improvement of anti-breast cancer drugs.

Can Antimalarial Phytochemicals be a Possible Cure for COVID-19? Molecular Docking Studies of Some Phytochemicals to SARS-CoV-2 3C-like Protease

2021 ◽  
Vol 21 ◽  
Author(s):  
Anamul Hasan ◽  
Khoshnur Jannat ◽  
Tohmina Afroze Bondhon ◽  
Rownak Jahan ◽  
Md Shahadat Hossan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
Binding Energies ◽  
Binding Affinities ◽  
Drug Candidates ◽  
Lead Compounds ◽  
High Binding ◽  
Main Protease ◽  
Acridone Alkaloid ◽  
First Time

Objective: To evaluate the efficacy of reported anti-malarial phytochemicals as lead compounds for possible drug development against COVID-19. Methods: An in silico approach was used in this study to determine through molecular docking the binding affinities and site of binding of these phytochemicals to the 3C-like protease of COVID-19 which is considered as the main protease of the virus. Results: A number of anti-malarial phytochemicals like apigenin-7-O-glucoside, decurvisine, luteolin-7-O-glucoside, sargabolide J, and shizukaols A, B, F, and G showed predicted high binding energies with G values of -8.0 kcal/mol or higher. Shizukaols F and B demonstrated the best binding energies of -9.5 and -9.8, respectively. The acridone alkaloid 5-hydroxynoracronycine also gave a predicted high binding energy of -7.9 kcal/mol. Conclusion: This is for the first time that decursivine and several shizukaols were reported as potential anti-viral agents. These compounds merit further studies to determine whether they can be effective drug candidates against COVID-19.

Molecular Docking Studies on Isocytosine Analogues as Xanthine Oxidase Inhibitors

Drug Research ◽  
2018 ◽  
Vol 68 (07) ◽  
pp. 395-402 ◽  
Author(s):  
Subhajit Roy ◽  
Bawneet Narang ◽  
Manish Gupta ◽  
Vikrant Abbot ◽  
Virender Singh ◽  
...  
Keyword(s):  
Xanthine Oxidase ◽  
Docking Studies ◽  
Binding Modes ◽  
Free Energies ◽  
Flexible Docking ◽  
Docking Simulations ◽  
Xanthine Oxidase Inhibitors ◽  
Best Fit ◽  
Insight Into ◽  
Binding Free Energies

AbstractFlexible docking simulations were carried out on a series of isocytosine analogs as xanthine oxidase (XO) inhibitors. This was done by analysing the interaction of these compounds at the active site of XO. The binding free energies of the analogs were calculated using GoldScore. The binding modes of the best-fit conformation were studied, providing some handy important interactions. The results obtained henceforth provided an insight into the pharmacophoric structural requirements for XO inhibition for this class of molecules.

scholarly journals A Computational Approach on the Activity of Hesperidin as Antagonist for Proteins of SARS-CoV-2

2021 ◽  
Vol 10 (3) ◽  
pp. 2571-2577
Keyword(s):  
Virtual Screening ◽  
Screening Tool ◽  
Viral Infections ◽  
Docking Studies ◽  
Computational Approach ◽  
Binding Energies ◽  
Spike Protein ◽  
Functional Component ◽  
Protein Inhibition ◽  
Drug Molecules

Spike proteins are a functional component in the viral infections of the SARS-CoV-2 virus that binds to the ACE2 receptors of the human cells. The naturally derived drugs like hesperidin show a higher affinity to avoiding the binding of the spike protein. Inhibition of the spike protein study represents the development of a new drug for SARS disease. Along with the hesperidin and its analogs have been found effective medicine to control SARS-CoV-2; the entire drug bank database was screened for strong analogous remedy like compounds as hesperidin. Virtual Screening and docking studies were intended for these molecules against spike protein with auto dock virtual screening tool and auto dock vena. The docking outcome showed that the compounds hesperitin, silibilin, and dihydromyricetin were having the highest binding energies, like -8 and -6.2. The current study indicates that the lead molecules have to be evaluated to improve prospective drug molecules.

scholarly journals Luteolin: A Potential Multiple Targeted Drug Effectively Inhibits Diabetes Mellitus Protein Targets

2021 ◽  
pp. 161-171
Author(s):  
Rakesh Davella ◽  
Estari Mamidala
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Docking ◽  
Docking Studies ◽  
Binding Energies ◽  
Binding Affinities ◽  
Protein Targets ◽  
Target Proteins ◽  
Dipeptidyl Peptidase 4 ◽  
Glucose Levels ◽  
Blood Glucose Levels

Background: Diabetes is a significant health problem that has reached worrisome proportions: almost half of the world's population now has diabetes. Diabetes mellitus, or diabetes, is a severe, long-term disease in which a person's blood glucose levels are elevated due to their body's inability to make any or enough insulin, or to properly utilise the insulin that it does produce. The chemicals extracted from medicinal plants were shown to be both safer and more bioactive than manufactured medicines. Objective: The goal of this research was to use molecular docking to find possible binding affinities of luteolin, a phytocompound from Rumex vesicarius L, to five target proteins, in order to find the lead molecule against diabetes. Methodology: One chemical was isolated from Rumex vesicarius L. leaves in this research. The binding affinity of the complexes was calculated using molecular docking studies. The docking procedure was carried out using AutoDock Tools 1.5.6, which brought the ligand together with the target proteins. Results: The binding energies of Luteolin with major Glutamine-fructose-6-phosphate amido transferase (GFAT1), Pancreatic α-Amylase, Forkhead box protein O1(FOX01), α--glucosidase, and Dipeptidyl peptidase-4 (DPP-4) were determined to be -6.89, -6.80, -6.36, -9.35, and -7.72 kcal. Conclusion: Our findings suggest that luteolin can target not only α--glucosidase but also DPP4 and other targets, suggesting that they may be used as type 2 diabetes mellitus inhibitors. We believe that this phytochemical, luteolin, may be utilised in preclinical studies as an anti-diabetic drug to combat diabetes mellitus.

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