Computational Screening of Phytochemicals from Medicinal plants as COVID-19 Inhibitors

<p>In this research a dataset of plant based bioactive compound was developed. A total of 101 phytochemicals were selected, virtually designed and its binding affinity with ACE enzyme was studied by molecular docking. Human ACE related carboxypeptidase and complex (PDB ID: 1R42) and (PDB ID: 6CS2) were selected for molecular docking studies as corona virus binds to ACE2 to enter into the host cell. Docking score results revealed that almost all selected phytochemicals binds to the pocket of the human ACE protein with high binding affinity and the scores were compared with chloroquine and hydroxychloroquine. The drug likeliness and ADMET analysis of all the screened compounds were performed. Two potential compound 6-α-acetoxygedunin and echitamine exhibited optimum binding with both the receptor.These phytochemicals can serve as lead molecule for further optimization and drug development against COVID-19. Therefore, it is predicted that the insights in the present study could be regarded valuable towards development of natural inhibitor of this virus.</p>

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Computational Screening of Phytochemicals from Medicinal plants as COVID-19 Inhibitors

10.26434/chemrxiv.12320273 ◽

2020 ◽

Author(s):

Alisha Khandelwal ◽

Tripti Sharma

Keyword(s):

Molecular Docking ◽

Medicinal Plants ◽

Drug Development ◽

Binding Affinity ◽

Bioactive Compound ◽

Docking Studies ◽

Computational Screening ◽

Natural Inhibitor ◽

Almost All ◽

High Binding Affinity

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Molecular docking studies of dihydropyridazin-3(2H)-one derivatives as Antifungal, antibacterial and anti-helmintic agents

World Journal of Advanced Research and Reviews ◽

10.30574/wjarr.2021.12.1.0476 ◽

2021 ◽

Vol 12 (1) ◽

pp. 186-214

Author(s):

Manish Devgun ◽

Sushil Prasad ◽

SukhbirLal Khokra ◽

Rakesh Narang

Keyword(s):

Molecular Docking ◽

Binding Affinity ◽

Rational Design ◽

Antimicrobial Agents ◽

Binding Free Energy ◽

Docking Studies ◽

Standard Drug ◽

Almost All ◽

Affinity Score ◽

Protein Active Site

Molecular docking is the identification of ligand’s correct binding geometry i.e pose in the binding site and estimation of its binding affinity for the rational design of drug molecule. The current study endeavored the high throughput insilico screening of 24 compounds docked with their respective protein using PyRx-Virtual Screening Tool software. Out of 24 compounds, almost all test compounds showed a very good binding affinity score. Fluconazole was used as a standard drug in case of Antifungal, Ciprofloxacin in case of Antibacterial, and Albendazole in case of Antihelmintics. More negative is the binding free energy score, more favorable is the pose for binding to protein active site. Based on H-bond interactions of these 24 compounds, Compounds 3a5, 3c3, 3d5, 3d6 were found to be the similar outcome for antifungal activity as fluconazole, Compound3a1 for antibacterial, and Compounds 3b5, 3d6 for the antihelmintic agent. Furthermore, the affinity of any small ligand molecules can be considered as an extraordinary tool in the field of drug design and offer imminent in future examination to build up potent antimicrobial agents.

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Molecular Docking Studies of Dihydropyridazin-3(2H)-one Derivatives as Anticonvulsant Agents

Asian Journal of Organic & Medicinal Chemistry ◽

10.14233/ajomc.2021.ajomc-p349 ◽

2021 ◽

Vol 6 (4) ◽

pp. 270-283

Author(s):

Sushil Prasad ◽

Sukhbir Lal Khokra ◽

Manish Devgun

Keyword(s):

Molecular Docking ◽

Binding Affinity ◽

Rational Design ◽

Docking Studies ◽

Standard Drug ◽

Branched Chain ◽

Almost All ◽

Derivatives Of ◽

Affinity Score ◽

Protein Active Site

Molecular docking is the identification of ligand’s correct binding geometry i.e. pose in the binding site and estimation of its binding affinity for rational design of drug molecule. The current study endeavored the high throughput in silico screening of 56 derivatives of dihydropyridazin-3(2H)-one docked with human cytosolic branched chain amino transferase using PyRx-virtual screening tool. Out of 56 compounds, almost all the test compounds showed very good binding affinity score. Gabapentin was used as standard drug which shows binding affinity of -6.2. On the basis of H-bond interactions, compounds 3, 9, 11, 25, 26, 31, 34, 39, 47, 48, 51, 54, 56 were found to be potent outcome for anticonvulsant activity. Compounds 11, 25, 39, 56 showed excellent H-bond interactions with protein active site, Among which compound 11 showed the outstanding interactions with acceptable bond length 2.34, 2.57, 2.62, 3.03 Å.

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A New Series Of 1,3-Dimethylxanthine Based Adenosine A2a Receptor Antagonists As A Non-Dopaminergic Treatment Of Parkinson’s Disease

Current Drug Discovery Technologies ◽

10.2174/1570163817666200827112252 ◽

2020 ◽

Vol 17 ◽

Author(s):

Suman Rohilla ◽

Ranju Bansal ◽

Puneet Chauhan ◽

Sonja Kachler ◽

Karl-Norbert Klotz

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Molecular Docking ◽

Binding Affinity ◽

Docking Studies ◽

Binding Modes ◽

Molecular Docking Studies ◽

In Silico Docking ◽

Adenosine A2a Receptor Antagonists ◽

The Impact

Background: Adenosine receptors (AR) have emerged as competent and innovative nondopaminergic targets for the development of potential drug candidates and thus constitute an effective and safer treatment approach for Parkinson’s disease (PD). Xanthine derivatives are considered as potential candidates for the treatment Parkinson’s disease due to their potent A2A AR antagonistic properties. Objective: The objectives of the work are to study the impact of substituting N7-position of 8-m/pchloropropoxyphenylxanthine structure on in vitro binding affinity of compounds with various AR subtypes, in vivo antiparkinsonian activity and binding modes of newly synthesized xanthines with A2A AR in molecular docking studies. Methods: Several new 7-substituted 8-m/p-chloropropoxyphenylxanthine analogues have been prepared. Adenosine receptor binding assays were performed to study the binding interactions with various subtypes and perphenazine induced rat catatonia model was used for antiparkinsonian activity. Molecular docking studies were performed using Schrödinger molecular modeling interface. Results: 8-para-substituted xanthine 9b bearing an N7-propyl substituent displayed the highest affinity towards A2A AR (Ki = 0.75 µM) with moderate selectivity versus other AR subtypes. 7-Propargyl analogue 9d produced significantly longlasting antiparkinsonian effects and also produced potent and selective binding affinity towards A2A AR. In silico docking studies further highlighted the crucial structural components required to develop xanthine derived potential A2A AR ligands as antiparkinsonian agents. Conclusion: A new series of 7-substituted 8-m/p-chloropropoxyphenylxanthines having good affinity for A2A AR and potent antiparkinsonian activity has been developed.

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Molecular Docking and Molecular Dynamics Simulation Studies of Triterpenes from Vernonia patula with the Cannabinoid Type 1 Receptor

International Journal of Molecular Sciences ◽

10.3390/ijms22073595 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3595

Author(s):

Md Afjalus Afjalus Siraj ◽

Md. Sajjadur Rahman ◽

Ghee T. Tan ◽

Veronique Seidel

Keyword(s):

Molecular Dynamics ◽

Molecular Docking ◽

Molecular Dynamics Simulation ◽

Binding Affinity ◽

Docking Studies ◽

Dynamics Simulation ◽

Simulation Studies ◽

Cannabinoid Type 1 Receptor ◽

Docking Approach

A molecular docking approach was employed to evaluate the binding affinity of six triterpenes, namely epifriedelanol, friedelin, α-amyrin, α-amyrin acetate, β-amyrin acetate, and bauerenyl acetate, towards the cannabinoid type 1 receptor (CB1). Molecular docking studies showed that friedelin, α-amyrin, and epifriedelanol had the strongest binding affinity towards CB1. Molecular dynamics simulation studies revealed that friedelin and α-amyrin engaged in stable non-bonding interactions by binding to a pocket close to the active site on the surface of the CB1 target protein. The studied triterpenes showed a good capacity to penetrate the blood–brain barrier. These results help to provide some evidence to justify, at least in part, the previously reported antinociceptive and sedative properties of Vernonia patula.

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MOLECULAR DOCKING STUDIES ON THE THERAPEUTIC TARGETS OF ALZHEIMER'S DISEASE (AChE AND BChE) USING NATURAL BIOACTIVE ALKALOIDS

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2016v8i12.14833 ◽

2016 ◽

Vol 8 (12) ◽

pp. 108

Author(s):

Punabaka Jyothi ◽

Kuna Yellamma

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Molecular Docking ◽

Binding Affinity ◽

Neurodegenerative Disorder ◽

Biological Activities ◽

Neuropsychiatric Symptoms ◽

Docking Studies ◽

Kcal Mole ◽

Molecular Docking Studies

Objective: Alzheimer’s disease (AD), a progressive neurodegenerative disorder with many cognitive and neuropsychiatric symptoms, is biochemically characterized by a significant decrease in the brain neurotransmitter Acetylcholine (ACh).Methods: In the present insilico study, six plant bioactive compounds namely Harmol, Vasicine, Harmaline, Harmine, Harmane and Harmalol (from P. Nigellastrum Bunge) were analyzed for their inhibitory role on AChE (Acetylcholinesterase) and BChE (Butyrylcholinesterase) activity by applying the molecular docking studies. Other parameters viz. determination of molecular interaction-based binding affinity values, protein-ligand interactions, Lipinski rule of five, functional properties and biological activities for the above compounds were also calculated by employing the appropriate bioinformatics tools.Results: The results of docking analysis clearly showed that Harmalol has highest binding affinity with AChE (-8.6 kcal/mole) and BChE (-8.0 kcal/mole) but it does not qualified the enzyme inhibitory activity, since it was exerted, and also has least percentage activity on AD and neurodegenerative disease. Whereas, the Harmine has been second qualified binding affinity (-8.4 kcal/mol) and first in other parameters when compared with Harmalol.Conclusion: Based on docking results and other parameters conducted, we are concluding that Harmine is the best compound for further studies to treat AD.Keywords: Alzheimer's disease (AD), Acetylcholinesterase, Butyrylcholinesterase, Lead Molecules

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SUSTAINED RELEASE TABLETS OF SORAFENIB-SILIBININ COMBINATIONS FOR THE TREATMENT OF HEPATOCELLULAR CARCINOMA

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2018v10i5.27597 ◽

2018 ◽

Vol 10 (5) ◽

pp. 117

Author(s):

Savita Mishra ◽

Sandhya Hora ◽

Vibha Shukla ◽

Mukul Das ◽

Harsha Kharkwal ◽

...

Keyword(s):

Molecular Docking ◽

Drug Release ◽

Sustained Release ◽

Cell Line ◽

Binding Affinity ◽

Drug Combination ◽

Docking Studies ◽

Molecular Docking Studies ◽

Weight Variation

Objective: The aim of this study was to develop polymer coated sustained release tablet using sorafenib and silibinin combination for the treatment of hepatocellular carcinoma.Methods: The qualitative analysis such as weight variation, friability, hardness, interaction studies, disintegration and in vitro release were performed to validate formulated tablets. We have maintained the acceptable official limits for weight variation, friability, hardness and disintegration time according to prescribed pharmacopoeial recommendation. In vitro drug release studies were performed using USP-II (paddle type) dissolution apparatus. The MTT assay was performed for assessment of Cell viability of drug combination for tablet formulation. Molecular docking studies have been performed to determine the combinatorial mode of action for the tablet formulation.Results: Friability and weight variation were less than 1% for each formulation, which were within range of prescribed pharmacopoeial recommendation. The hardness of 20 tablets showed 5-6.5Kg/cm2 for all formulations 5-6.5Kg/cm2. The optimized formulation resulted in 98% drug release after 28 h. The present study reports the synergistic effects of drug combination to inhibit cell growth in HepG2 cell line. Molecular docking studies showed that sorafenib has high binding affinity for B-Raf vascular endothelial growth factor receptor β and protein kinase B. Silibinin showed binding affinity with MAP kinase-11, protein phosphatase 2 A and tankyrase.Conclusion: The present study reports for the first time a novel formulation for sustained release and reduced toxicity of sorafenib with enhanced inhibitory effect of the drug combination on cancerous hepatic cell line as well collaborative mechanism of action for the formulation.

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MOLECULAR DOCKING AND PHARMACOKINETIC PREDICTION OF HERBAL DERIVATIVES AS MALTASE-GLUCOAMYLASE INHIBITOR

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i9.19337 ◽

2017 ◽

Vol 10 (9) ◽

pp. 392 ◽

Cited By ~ 1

Author(s):

Peter Juma Ochieng ◽

Tony Sumaryada ◽

Daniel Okun

Keyword(s):

Molecular Docking ◽

Surface Area ◽

Docking Studies ◽

Polar Surface Area ◽

Autodock Vina ◽

Standard Drug ◽

Lipinski’S Rule ◽

Structure Activity ◽

Topological Polar Surface Area ◽

High Binding Affinity

Objective: To perform molecular docking and pharmacokinetic prediction of momordicoside F2, beta-sitosterol, and cis-N-feruloyltyramine herbal derivatives as maltase-glucoamylase (MGAM) inhibitors for the treatment of diabetes.Methods: The herbal derivatives and standard drug miglitol were docked differently onto MGAM receptor using AutoDock Vina software. In addition, Lipinski’s rule, drug-likeness, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties were analyzed using Molinspiration, ADMET structure–activity relationship, and prediction of activity spectra for substances online tools.Results: Docking studies reveal that momordicoside F2, beta-sitosterol, and cis-N-feruloyltyramine derivatives have high binding affinity to the MGAM receptor (−7.8, −6.8, and −6.5 Kcal/Mol, respectively) as compared to standard drug miglitol (−5.3 Kcal/Mol). In addition, all the herbal derivatives indicate good bioavailability (topological polar surface area <140 Ȧ and Nrot <10) without toxicity or mutagenic effects.Conclusion: The molecular docking and pharmacokinetic information of herbal derivatives obtained in this study can be utilized to develop novel MGAM inhibitors having antidiabetic potential with better pharmacokinetic and pharmacodynamics profile.

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Molecular Docking Senyawa Gingerol dan Zingiberol pada Tanaman Jahe sebagai Penanganan COVID-19

Jurnal e-Biomedik ◽

10.35790/ebm.v9i1.32361 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Belinda D. P. M. Ratu ◽

Widdhi Bodhi ◽

Fona Budiarso ◽

Billy J. Kepel ◽

. Fatimawali ◽

...

Keyword(s):

Molecular Docking ◽

Binding Affinity ◽

Amino Acid Residues ◽

Autodock Vina ◽

Discovery Studio ◽

Main Protease ◽

Docking Method ◽

Pubmed Database ◽

Almost All ◽

The Impact

Abstract: COVID-19 is a new disease. Many people feel the impact of this disease. There is no definite cure for COVID-19, so many people use traditional medicine to ward off COVID-19, including ginger. This study aims to determine whether there is an interaction between compounds in ginger (gingerol and zingiberol) and the COVID-19’s main protease (6LU7). This study uses a molecular docking method using 4 main applications, namely Autodock Tools, Autodock Vina, Biovia Discovery Studio 2020, and Open Babel GUI. The samples used were gingerol and zingiberol compounds in ginger plants downloaded from Pubchem. The data used in this study used Mendeley, Clinical Key, and PubMed database. The study showed that almost all of the amino acid residues in the gingerol compound acted on the 6LU7 active site, whereas the zingiberol did not. The results of the binding affinity of ginger compounds, both gingerol and zingiberol, do not exceed the binding affinity of remdesivir, a drug that is widely researched as a COVID-19 handling drug. In conclusion, gingerol and zingiberol compounds in ginger can’t be considered as COVID-19’s treatment.Keywords: molecular docking, gingerol, zingiberol Abstrak: COVID-19 merupakan sebuah penyakit yang baru. Banyak masyarakat yang merasakan dampak dari penyakit ini. Belum ada pengobatan pasti untuk menyembuhkan COVID-19, sehingga banyak masyarakat yang menggunakan pengobatan tradisional untuk menangkal COVID-19, termasuk jahe. Penelitian ini bertujuan untuk mengetahui apakah ada interaksi antara senyawa pada jahe (gingerol dan zingiberol) dengan main protease COVID-19 (6LU7). Penelitian ini menggunakan metode molecular docking dengan menggunakan 4 aplikasi utama, yaitu Autodock Tools, Autodock Vina, Biovia Discovery Studio 2020, dan Open Babel GUI. Sampel yang digunakan yaitu senyawa gingerol dan zingiberol pada tanaman jahe yang diunduh di Pubchem. Data yang digunakan dalam penelitian ini menggunakan database Mendeley, Clinical Key, dan PubMed. Penelitian menunjukkan bahwa hampir semua residu asam amino pada senyawa gingerol bekerja pada sisi aktif 6LU7, sedangkan tidak demikian pada zingiberol. Hasil binding affinity senyawa jahe, baik gingerol maupun zingiberol tidak melebihi binding affinity remdesivir, obat yang banyak diteliti sebagai obat penanganan COVID-19. Sebagai simpulan, senyawa gingerol dan zingiberol pada tanaman jahe tidak dapat dipertimbangkan sebagai penanganan COVID-19Kata Kunci: molecular docking, gingerol, zingiberol

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Identification of Potent Inhibitors against Aurora Kinase A Using Molecular Docking and Molecular Dynamics Simulation Studies

10.20944/preprints201908.0238.v1 ◽

2019 ◽

Author(s):

Sathishkumar Chinnasamy ◽

Gurudeeban Selvaraj ◽

Aman Chandra Kaushik ◽

Satyavani Kaliamurthi ◽

Asma Sindhoo Nangraj ◽

...

Keyword(s):

Molecular Dynamics ◽

Molecular Docking ◽

Molecular Dynamics Simulation ◽

Binding Affinity ◽

Aurora Kinase ◽

Dynamics Simulation ◽

Simulation Studies ◽

Aurora Kinase A ◽

High Binding Affinity ◽

Kinase A

Aurora kinase A (AURKA) is a normal cell proliferation-inducing enzyme encoded by AURKA gene, with over-expression observed in different types of malignancies. Hence, the goal is to find potential inhibitors against AURKA. In this study, molecular docking, Standard Precision and Extra Precision methods were employed. After the docking study, the ligands showed an extremely low binding score which suggested very high binding affinity of the ligands. Furthermore, Quantum polarized ligand docking (QPLD) was performed to predict the binding status of the molecules. Based on the binding affinity, the top four compounds were chosen for further analysis. The docked complexes were further analyzed in explicit water conditions using 100 ns molecular dynamics simulations and binding free energy calculation. Then, density functional theory (DFT) calculation was used to calculate the molecular properties of the molecules. Finally, systems biology experiments validated the molecular docking and molecular dynamics simulation studies and indicated that quercetin, kaempferol, luteolin and rutin could inhibit the AURKA. The results show that, these four molecules have high binding affinity to the AURKA and significant interactions (LEU139, GLU211and ALA213) were also identified with the hinge region of Aurora kinase A. Thus, LEU139, GLU211, and ALA213 were identified as the crucial protein mechanisms.

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