scholarly journals Inhibition of RNA-dependent RNA polymerase from SARSCoV-2 by compounds in Vangag herbal preparation: an in silico evaluation

2021 ◽  
Vol 17 (2) ◽  
pp. 88-95
Author(s):  
Kakjing D. Falang ◽  
Catherine O. Poyi ◽  
Jacob A. Kolawole
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Antiviral Agents ◽  
Therapeutic Agents ◽  
Therapeutic Effects ◽  
Binding Affinities ◽  
High Concentration ◽  
Discovery Studio ◽  
Herbal Formulation ◽  
Viral Target

Coronavirus disease (COVID-19) has presented unprecedented challenges to healthcare systems worldwide. There are no proven effective therapeutic agents or vaccines. Some antiviral agents and micronutrients have been repurposed for the management. There are claims of herbal preparations with therapeutic effects. Vangag herbal formulation for the management of COVID-19 is a combination of six plants. Molecular docking and virtual screening were used for the study. Ligands and protein target for molecular docking were prepared in Autodock Tools using PyRx 0.8 package. 3D structures of 24 phytochemicals in Vangag were downloaded from PubChem and optimized in Discovery Studio 4.5 visualizer. Nine agents currently used for management of COVID-19 were also downloaded and included in the ligand library to serve as control. Results of the binding affinities of phytochemicals in constituentplants of Vangag to SARS-CoV-2 molecular target (7BV2.pdb) were ranked from 1 to 21. Kolaviron (binding affinity -8.1 Kcal/mol) ranked 1, Ritonavir 5, Remdesivir 6, Quinine 7, Hydroxychloroquine 9, Chloroquine 18 and the least Allicin 21 (binding affinity -3.7 Kcal/mol). Phytochemicals in Vangag have good binding affinity to COVID-19 viral target proteins. Vangag also contains high concentration of zinc and other micronutrients, making it a promising formula for management of COVID-19. Keywords: COVID-19; SARS-CoV-2; Molecular docking; Herbal formulation

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

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

scholarly journals Ligand Based 3D-QSAR Pharmacophore, Molecular Docking and Adme to Identify Potential Fibroblast Growth Factor Receptor 1 Inhibitors 

2020 ◽  
Author(s):  
Zizhong Tang ◽  
Lu Huang ◽  
Xiaoli Fu ◽  
Haoxiang Wang ◽  
Biao Tang ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Growth Factor Receptor ◽  
Pharmacophore Model ◽  
3D Qsar ◽  
Drug Carriers ◽  
Therapeutic Effects ◽  
Lipinski’S Rule ◽  
Discovery Studio ◽  
Zinc Database

Abstract The FGF/FGFR system may affect tumor cells and stromal microenvironment through autocrine and paracrine stimulation, thereby significantly promoting oncogene transformation and tumor growth. Abnormal expression of FGFR1 in cells is considered to be the main cause of tumorigenesis and a potential target for the treatment of cancer. In this study, a combination of structure-based drug carriers and molecular docking-based virtual screening was used to screen new potential FGFR1 inhibitors. Twenty-one known inhibitors were collected as training sets to establish a 3D-QSAR pharmacophore model, and cost analysis, test set validation, and Fischer randomization test were used to validate the efficiency of the pharmacophore model. In Accelrys Discovery Studio 2016, the zinc database was filtered by Lipinski's Rule of Five and SMART's filtration. Then, Hypo01 was used for virtual screening of ZINC database. Compounds with predicted activity values less than 1 μM were molecularly docked with FGFR1 protein crystals, the docking results were observed, and the interaction between compounds and targets was studied. The absorption, distribution, metabolism and excretion (ADME) and toxicity of potential inhibitors were studied, and a compound with new structural scaffolds were obtained. It could be further studied to explore their better therapeutic effects.

scholarly journals Design of more potent quinazoline derivatives as EGFRWT inhibitors for the treatment of NSCLC: a computational approach

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Muhammad Tukur Ibrahim ◽  
Adamu Uzairu ◽  
Sani Uba ◽  
Gideon Adamu Shallangwa
Keyword(s):  
Lung Cancer ◽  
Molecular Docking ◽  
Binding Affinity ◽  
Positive Control ◽  
Computational Approach ◽  
Tyrosine Kinase Receptor ◽  
Binding Affinities ◽  
Binding Interaction ◽  
Pharmacokinetic Properties ◽  
Inhibitory Activities

Abstract Background Lung cancer remains the leading and deadly type of cancer worldwide. It was estimated to account for about 25% of the 7 million people that died as a result of cancer-related issues/mortality every year in the world. Non-small cell lung cancer (NSCLC) is the lethal/deadly class of lung cancer with nearly 1.5 million reported cases and less than 20% survival rate. Therefore, it becomes necessary to explore more effective NSCLC drugs. Result A computational approach was employed here to design ten new EGFRWT inhibitors using compound 18 as a template for the design identified with the best binding affinity and good pharmacokinetic properties previously reported in our work. The modeled inhibitory activities of these newly designed EGFRWT inhibitors (range from 7.746966 to 11.09261) were better than that of the hit compound with pIC50 of 7.5639 and gefitinib the positive control with pIC50 of 5.879426. The ligand-binding interaction between these newly designed EGFRWT inhibitors and the EGFR tyrosine kinase receptor as shown in Table 3 was investigated and elucidated using molecular docking protocol. Based on the molecular docking results, the binding affinities of these newly designed EGFRWT inhibitors were found to be between − 8.8 and − 9.5 kcal/mol. The designed compound SFD10 has the highest binding affinity of − 9.5 kcal/mol followed by compound SFD8 (with a binding affinity of − 9.3 kcal/mol), then by compound SFD9 and 4 (each with a binding affinity of − 9.3 kcal/mol). None of them was found to have more than one violation of the filtering criterion used in this study thereby showing good ADMET properties. Conclusion The modeled inhibitory activities and binding affinities of these newly designed EGFRWT inhibitors were found to be higher than that of the template compound and the control (gefitinib) used in this research. They were also seen to be non-toxic with good pharmacokinetic properties.

scholarly journals Molecular Docking Analysis Of Some Phytochemicals On Two SARS-CoV-2 Targets: Potential Lead Compounds Against Two Target Sites of SARS-CoV-2 Obtained from Plants

2020 ◽  
Author(s):  
Amaka Ubani ◽  
Francis Agwom ◽  
Oluwatoyin RuthMorenikeji ◽  
Shehu Nathan ◽  
Pam Luka ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Potential Candidate ◽  
Binding Affinities ◽  
Protein Targets ◽  
Docking Analysis ◽  
Lead Compounds ◽  
Target Sites ◽  
Antiviral Activities ◽  
Molecular Docking Analysis

AbstractCOV spike (S) glycoprotein and Mpro are two key targets that have been identified for vaccines and drug development against the COVID-19 disease. Virtual screening of some compounds of plants origin that have shown antiviral activities were carried out on the two targets, 6lu7 and 6vsb by docking with the PyRx software. The binding affinities were compared with other compounds and drugs already identified as potential ligands for 6lu7 and 6vsb as well as Chloroquine and hydroxychloroquine. The docked compounds with best binding affinities were also filtered for drug likeness using the SwissADME and PROTOX platforms on the basis of Physicochemical properties and toxicity respectively. The docking results revealed that scopodulcic acid and dammarenolic acid had the best binding affinity on the s-glycoprotein and Mpro protein targets respectively. Silybinin also demonstrated a good binding affinity to both protein targets making it a potential candidate for further evaluation as repurposed candidate for SARS COV2 with likelihood of having a multitarget activity.

scholarly journals IDENTIFICATION OF POSSIBLE MOLECULAR TARGETS OF POTENTIAL ANTI-PARKINSON DRUGS BY PREDICTING THEIR BINDING AFFINITIES USING MOLECULAR DOCKING TECHNIQUE

2018 ◽  
Vol 11 (14) ◽  
pp. 28
Author(s):  
Maguemga Homsi Chanceline Dorice ◽  
Navneet Khurana ◽  
Neha Sharma ◽  
Gopal L Khatik
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Energy Minimization ◽  
Molecular Targets ◽  
Mechanistic Study ◽  
Binding Affinities ◽  
Autodock Vina ◽  
3D Structures ◽  
Mao B ◽  
3D Software

Objective: Mechanistic study of newly reported anti-Parkinson agents by molecular docking to predict possible target.Methods: Structures of newer drugs known anti-Parkinson agents were drawn using ChemBioDraw 2D software. Thereafter, they were converted to 3D structures using ChemBioDraw 3D software in which they were subjected to energy minimization using the MM2 method and then saved as PDB extension files, which can be accessed using the AutoDock Vina (ADT) interface. ADT 1.5.6 software version was used for molecular docking study.Results: Various molecular targets were selected (D2/D3, D2, A2A, and MAO-B) and studied for Pardoprunox, Istradefylline, Rasagiline, and Bromocriptine. Pardoprunox, Istradefylline, and Bromocriptine had more affinity with their corresponding receptor with −6.9, −8.5, and −9.4 kcal/mol binding affinity, respectively, except Rasagiline, who has less affinity with its corresponding receptor (−6.4kcal/mol) and shown better affinity with 3pbl receptor (−6.7 kcal/mol).Conclusion: Pardoprunox, Istradefylline, and Bromocriptine were found to act on D2/D3 (3pbl), A2A (3pwh), and D2 (4yyw), respectively, whereas Rasagiline found to be act on D2/D3 (3pbl) receptor. The results help in prediction of mechanism and interaction to various Parkinson’s disease targets.

scholarly journals Chemical Profiles and Pharmacological Properties with in Silico Studies on Elatostema papillosum Wedd

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 809 ◽  
Author(s):  
Md. Zia Uddin ◽  
Arkajyoti Paul ◽  
Ahmed Rakib ◽  
Saad Ahmed Sami ◽  
Shafi Mahmud ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Serotonin Receptor ◽  
Computational Study ◽  
Biological Activities ◽  
Binding Affinities ◽  
In Silico Studies ◽  
Cox 2 ◽  
Cox 1

The current study attempted, for the first time, to qualitatively and quantitatively determine the phytochemical components of Elatostema papillosum methanol extract and their biological activities. The present study represents an effort to correlate our previously reported biological activities with a computational study, including molecular docking, and ADME/T (absorption, distribution, metabolism, and excretion/toxicity) analyses, to identify the phytochemicals that are potentially responsible for the antioxidant, antidepressant, anxiolytic, analgesic, and anti-inflammatory activities of this plant. In the gas chromatography-mass spectroscopy analysis, a total of 24 compounds were identified, seven of which were documented as being bioactive based on their binding affinities. These seven were subjected to molecular docking studies that were correlated with the pharmacological outcomes. Additionally, the ADME/T properties of these compounds were evaluated to determine their drug-like properties and toxicity levels. The seven selected, isolated compounds displayed favorable binding affinities to potassium channels, human serotonin receptor, cyclooxygenase-1 (COX-1), COX-2, nuclear factor (NF)-κB, and human peroxiredoxin 5 receptor proteins. Phytol acetate, and terpene compounds identified in E. papillosum displayed strong predictive binding affinities towards the human serotonin receptor. Furthermore, 3-trifluoroacetoxypentadecane showed a significant binding affinity for the KcsA potassium channel. Eicosanal showed the highest predicted binding affinity towards the human peroxiredoxin 5 receptor. All of these findings support the observed in vivo antidepressant and anxiolytic effects and the in vitro antioxidant effects observed for this extract. The identified compounds from E. papillosum showed the lowest binding affinities towards COX-1, COX-2, and NF-κB receptors, which indicated the inconsequential impacts of this extract against the activities of these three proteins. Overall, E. papillosum appears to be bioactive and could represent a potential source for the development of alternative medicines; however, further analytical experiments remain necessary.

scholarly journals HIGH-THROUGHPUT SCREENING AND DYNAMIC STUDIES OF SELECTED COMPOUNDS AGAINST SARS-COV-2

2022 ◽  
pp. 251-260
Author(s):  
RATUL BHOWMIK ◽  
RANAJIT NATH ◽  
SAMEER SHARMA ◽  
RATNA ROY ◽  
RIYA BISWAS
Keyword(s):  
Drug Delivery ◽  
Molecular Docking ◽  
Binding Affinity ◽  
High Throughput Screening ◽  
In Silico Analysis ◽  
Inhibitory Effect ◽  
Binding Affinities ◽  
Pubchem Database ◽  
Potential Inhibitors ◽  
3Cl Protease

Objective: This study was aimed to analyze the inhibitory effect of the drugs used in nanocarrier as well as nanoparticles formulation based drug delivery system selected from PubChem database literature against 3CLpro (3C-like protease) receptor of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) by implementing several in silico analysis techniques. Methods: This paper detailed a molecular docking-based virtual screening of 5240 compounds previously utilized in nanoparticle and nanocarrier drug delivery systems utilizing AutoDock Vina software on 3CL protease to discover potential inhibitors using a molecular docking technique. Results: According to the results of the screening, the top two compounds, PubChem Id 58823276 and PubChem Id 60838 exhibited a high affinity for the 3CL protease binding region. Their binding affinities were-9.6 and-8.5 kJ/mol, indicating that they were tightly bound to the target receptor, respectively. These results outperformed those obtained using the co-crystallized native ligand, which exhibited a binding affinity of-7.4 kJ/mol. PubChem Id 60838, the main hit compound in terms of both binding affinity and ADMET analysis, displayed substantial deformability after MD simulation. As a result of the VS and molecular docking techniques, novel 3CL protease inhibitors from the PubChem database were discovered using the Lipinski rule of five and functional molecular contacts with the target protein, as evidenced by the findings of this work. Conclusion: The findings suggest that the compounds discovered may represent attractive opportunities for the development of COVID-19 3CLpro inhibitors and that they need further evaluation and investigation.

scholarly journals Molecular docking analysis of selected phytochemicals on two SARS-CoV-2 targets

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 1157
Author(s):  
Amaka Ubani ◽  
Francis Agwom ◽  
Oluwatoyin Ruth Morenikeji ◽  
Nathan Yakubu Shehu ◽  
Emmanuel Arinze Umera ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Drug Formulation ◽  
Potential Candidate ◽  
Binding Affinities ◽  
Plant Origin ◽  
Protein Targets ◽  
Docking Analysis ◽  
Antiviral Activities

Background: The coronavirus spike (S) glycoprotein and M protease are two key targets that have been identified for vaccines and drug development against COVID-19. Methods: Virtual screening of some compounds of plant origin that have shown antiviral activities were carried out on the two targets, the M protease (PDB ID 6LU7) and S glycoprotein (PDB ID 6VSB), by docking with PyRx software. The binding affinities were compared with other compounds and drugs already identified as potential ligands for the M protease and S glycoprotein, as well as chloroquine and hydroxychloroquine. The docked compounds with best binding affinities were also filtered for drug likeness using the SwissADME and PROTOX platforms on the basis of physicochemical properties and toxicity, respectively. Results: The docking results revealed that scopadulcic acid and dammarenolic acid had the best binding affinity for the S glycoprotein and Mpro protein targets, respectively. Silybinin, through molecular docking, also demonstrated good binding affinity for both protein targets making it a potential candidate for further evaluation as repurposed candidate for SARS-CoV-2, with likelihood of having multitarget activity as it showed activities for both targets. Conclusions: The study proposes that scopadulcic acid and dammarenolic acid be further evaluated in vivo for drug formulation against SARS-COV-2 and possible repurposing of Silybinin for the management of COVIV-19.

scholarly journals Computational analysis of the interaction of limonene with the fat mass and obesity-associated protein

2021 ◽  
Vol 8 (1) ◽  
pp. 154-160
Author(s):  
Muhammad Zeeshan Ahmed ◽  
Shahzeb Hameed ◽  
Mazhar Ali ◽  
Ammad Zaheer
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Fat Mass ◽  
Computational Analysis ◽  
Physical Interaction ◽  
Autodock Vina ◽  
Inhibitory Interaction ◽  
Protein Association ◽  
Discovery Studio ◽  
Bioinformatic Tool

This study aimed to predict the binding affinity, orientation, and physical interaction between limonene and fat mass and obesity-associated protein. The mechanism of limonene and protein association was explored by molecular docking, a bioinformatic tool. The results of association were compared with the reported results of the anti-obesity drug such as orlistat and with the flavonoids. AutoDock Vina tools were used for the molecular docking of limonene with fat mass and obesity-associated protein. PyMol and Discovery Studio Visualizer were used to visualize the results of this docking. The binding affinity of limonene was higher (Least negative G) than the orlistat and flavonoids such as Daidzein, Exemestane, Kaempherol, Letrozole, And Rutin. It is conducted in this study that the Limonene can alleviate obesity by making an interaction with the fat mass and obesity-associated protein. This inhibitory interaction was greater as compared to other reported phytochemicals and drugs.

Molecular docking study of Lens culinaris L. phytochemicals to NS3-NS2B protease of dengue virus serotype 2

2021 ◽  
Vol 1 (1) ◽  
pp. 26-37
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Dengue Virus ◽  
Binding Affinity ◽  
Lens Culinaris ◽  
Binding Affinities ◽  
High Binding ◽  
Virus Serotype ◽  
Dengue Virus Serotype 2 ◽  
High Binding Affinity

Forty-three phytochemicals present in Lens culinaris were evaluated through in-silico molecular docking studies for their binding affinities to the NS2B-NS3 activator-protease complex of dengue virus serotype 2 (DENV-2). Among the various compounds tested, flavonoids (flavanols,favonols, proanthocyanidins, flavanones, flavones, and anthocyanins) demonstrated high binding affinities for the protease complex. Eriodictyol-7-O-rutinoside showed the least predicted binding energy at -9.1 kcal/mol followed by luteolin-7-O-glucoside at -8.8 kcal/mol. Glycosidic linkages appeared to enhance the binding affinities of flavonoids, aldohexoses being more potent than aldopentoses. Besides flavonoids, other classes of compounds demonstrating high binding affinities for the protease were carotenoids, phytosterols, and polyphenolic compounds like resveratrol and trans-resveratrol 3-O-b-glucoside (piceid), the latter showing predicted binding energy of -8.5 kcal/mol versus predicted binding energy of -7.2 kcal/mol for resveratrol. The 2D interactions of four high binding affinity compounds like eriodictyol, eriodictyol-7-O-rutinoside, catechin gallate, and luteolin-7-O-glucoside showed that all four compounds bound to the active site of the NS3 protease and not to the activator NS2B. Lys74 of NS3 was the common amino acid interacting with all four phytochemicals. Analysis of physicochemical properties of the compounds (Lipinski's Rule of 5) showed that the high binding affinity compounds have less than two violations, indicating that they can serve as useful lead compounds or as dengue virus serotype 2 therapeutics.

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