scholarly journals Anticancer Screening of the Phytochemicals Present in the Medicinal Plant Vitex Negundo Against Mutant Anaplastic Lymphoma Kinase (ALK) Protein: An In-Silico Approach

2019 ◽  
Vol 12 (2) ◽  
pp. 993-1000 ◽  
Author(s):  
D. Anusha ◽  
S. Sharanya ◽  
Ramya Ramya ◽  
Darling Chellathai David
Keyword(s):  
Molecular Docking ◽  
Medicinal Plant ◽  
Anaplastic Lymphoma Kinase ◽  
Natural Compounds ◽  
Binding Energies ◽  
Vitex Negundo ◽  
Molecular Docking Study ◽  
Selective Toxicity ◽  
Molegro Virtual Docker ◽  
Anaplastic Lymphoma

The lymphomas are a heterogeneous group of cancer of the lymphocytes and the lymphatic system and accounts for up to 3% of all malignancies.1 Most of the drugs currently used for the treatment of lymphoma produce various side effects, hence in this study, we focus on natural compounds, obtained from the medicinal plant Vitex negundo, which exhibits selective toxicity against cancer cells. The objective of this research was to formulate the binding energies and interaction of selected phytochemicals present in the medicinal plant Vitex negundo2 against anaplastic lymphoma kinase protein, which is overexpressed in an anaplastic large cell lymphoma.3, 4,5 The structure of mutant human anaplastic lymphoma kinase protein was retrieved from the Protein Data Bank (PDB ID:4ANL ) and the 3D chemical structure of the phytochemicals present in the medicinal plant Vitex negundo was obtained from the PubChem database. Molecular docking study was performed for these natural compounds to evaluate and analyze their anti-lymphoma-cancer activity. A total of 16 compounds present in Vitex negundo, based on a comprehensive literature survey was selected for this molecular screening. Molecular docking analysis was carried out by Molegro Virtual Docker software, to screen the 16 chosen compounds and rank them according to their binding affinity towards the site of interaction of the oncoprotein, anaplastic lymphoma kinase. Out of the 16 screened phytocompounds, only 4 compounds showed promising interactions against the oncoprotein ALK (4ANL). 6’-p-hydroxybenzoyl mussaenosidic acid exhibited a very good binding with a molecular docking score of -127.723 kcal/mol, ranking first among the compounds screened. This was followed by Betulinic acid, Viridiflorol and protocatechuic acid with molecular docking scores of -95.596 kcal/mol, -76.1648 kcal/mol and -63.0854 kcal/mol and - respectively. The docking scores from the above study shows that the phytocompounds present in Vitex negundo extract exhibits an effective inhibitory effect against anaplastic lymphoma kinase protein that is over expressed in lymphoma.

Screening of Potent Inhibitors Against 2019 Novel Coronavirus (Covid-19) from Alliumsativum and Allium cepa: An In Silico Approach

2020 ◽  
Vol 11 (1) ◽  
pp. 7981-7993
Keyword(s):  
Molecular Docking ◽  
Allium Cepa ◽  
In Silico ◽  
Treatment Options ◽  
Natural Compounds ◽  
Binding Energies ◽  
Drug Candidate ◽  
Molecular Docking Study ◽  
Standard Drug ◽  
Main Protease

The infection of the global COVID-19 pandemic and the absence of any possible treatment options warrants the use of all available resources to find effective drugs against this scourge. Various ongoing researches have been searching for the new drug candidate against COVID-19 infection. The research objective is based on the molecular docking study of inhibition of the main protease of COVID-19 by natural compounds found in Allium sativum and Allium cepa. Lipinski rule of five and Autodock 4.2 was used by using the Lamarckian Genetic Algorithm to perform Molecular docking to analyze the probability of docking. Further, ADME analysis was also performed by using SwissADME, which is freely available on the web. In the present study, we identified S-Allylcysteine sulfoxide (Alliin), S-Propyl cysteine, S-Allylcysteine, S-Ethylcysteine, S-Allylmercaptocysteine, S-Methylcysteine, S-propyl L-cysteine with binding energies (-5.24, -4.49, -4.99, -4.91, -4.79, -4.76, -5.0 kcal/mol) as potential inhibitor candidates for COVID-19. Out of 7 selected compounds, alliin showed the best binding efficacy with target protein 6LU7. In silico ADME analysis revealed that these compounds are expected to have a standard drug-like property as well. Our findings propose that natural compounds from garlic and onion can be used as potent inhibitors against the main protease of COVID-19, which could be helpful in combating the COVID-19 pandemic.

scholarly journals Identification of Potent COVID-19 Main Protease (Mpro) Inhibitors from Natural Polyphenols: An in Silico Strategy Unveils a Hope against CORONA

2020 ◽  
Author(s):  
Sevki Adem ◽  
Volkan Eyupoglu ◽  
Iqra Sarfraz ◽  
Azhar Rasul ◽  
Muhammad Ali
Keyword(s):  
Molecular Docking ◽  
Drug Target ◽  
Docking Study ◽  
Binding Energies ◽  
Therapeutic Drug ◽  
Molecular Docking Study ◽  
Molegro Virtual Docker ◽  
Main Protease ◽  
Chinese Researcher ◽  
Native Ligand

COVID-19, a rapidly spreading new strain of coronavirus, has affected more than 150 countries and received worldwide attention. The lack of efficacious drugs or vaccines against SARS-CoV-2 has further worsened the situation. Thus, there is an urgent need to boost up research for the development of effective therapeutics and affordable diagnostic against COVID-19. The crystallized form of SARS-CoV-2 main protease (Mpro) was demonstrated by a Chinese researcher Liu et al. (2020) which is a novel therapeutic drug target. This study was conducted to evaluate the efficacy of medicinal plant-based bioactive compounds against COVID-19 Mpro by molecular docking study. Molecular docking investigations were performed by using Molegro Virtual Docker 7 to analyze the inhibition probability of these compounds against COVID-19. COVID-19 Mpro was docked with 80 flavonoid compounds and the binding energies were obtained from the docking of (PDB ID: 6LU7: Resolution 2.16 Å) with the native ligand. According to obtained results, hesperidin, rutin, diosmin, apiin, diacetylcurcumin, (E)-1-(2-Hydroxy-4-methoxyphenyl)-3-[3-[(E)-3-(2-hydroxy-4- methoxyphenyl)-3-oxoprop-1-enyl]phenyl]prop-2-en-1-one, and beta,beta'-(4-Methoxy-1,3- phenylene)bis(2'-hydroxy-4',6'-dimethoxyacrylophenone have been found as more effective on COVID-19 than nelfinavir. So, this study will pave a way for doing advanced experimental research to evaluate the real medicinal potential of these compounds to cure COVID-19.

scholarly journals A Molecular Docking Study of N-Ferrocenylmethylnitroanilines as Potential Anticancer Drugs

2016 ◽  
Vol 2 ◽  
pp. 5-12 ◽  
Author(s):  
Touhami Lanez ◽  
Elhafnaoui Lanez
Keyword(s):  
Escherichia Coli ◽  
Molecular Docking ◽  
Protein Structure ◽  
Dna Gyrase ◽  
Data Bank ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Molegro Virtual Docker ◽  
Gyrase A

In the present study, the interaction of the protein structure of Escherichia coli DNA Gyrase-A (EcGyr-A) extracted from protein data bank (PDB Code: 1AB4) with ligands N-ferrocenylmethyl-2-nitroaniline (2FMNA), N-ferrocenylmethyl-3-nitroaniline (3FMNA) and N-ferrocenylmethyl-4-nitroaniline (4FMNA) were investigated by performing docking studies using the Molegro Virtual Docker (MVD) software. The results obtained showed that the best poses which is derived from MolDock score for Escherichia coli DNA Gyrase-A were respectively equal to-92.0111, -96.0866 and-95.6808 with reranking score equal to-40.9575, -73.4476 and-73.6423. Calculations revealed that 3FMNA react strongly with EcGyr-A followed by 4-FMNA and 2-FMNA.

scholarly journals Molecular Docking Analysis of Chloroquine and Hydroxychloroquine and Design of Anti-SARS-CoV2 Protease Inhibitor

2020 ◽  
Vol 14 (10) ◽  
pp. 52
Author(s):  
Usman Abdulfatai ◽  
Adamu Uzairu ◽  
Gideon Adamu Shallangwa ◽  
Sani Uba
Keyword(s):  
Amino Acids ◽  
Molecular Docking ◽  
Binding Energy ◽  
Binding Site ◽  
Docking Simulation ◽  
Binding Energies ◽  
Drug Candidate ◽  
Molecular Docking Study ◽  
Docking Analysis ◽  
Molecular Docking Analysis

In this present investigation, simulated molecular docking study of chloroquine and hydroxychloroquine compounds were investigated on the SARS-CoV2 enzyme to determine the types of amino acids responsible for the biochemical reaction at the binding site. A structure-based docking design technique was explored in designing a novel derivative of chloroquine for the treatment and management of new COVID 19 disease. To achieve this, the molecular docking simulation method was used to investigate the level of chloroquine and hydroxychloroquine (Drugs presently under clinical trial) interactions on SARS-CoV2 enzyme (a causative agent of COVID 19 disease). Chloroquine and hydroxychloroquine which has been debated as drugs for the management of COVID 19 were subjected to molecular docking analysis, and the binding energies generated were found to be -6.1 kcal/mol and -6.8 kcal/mol respectively. Moreover, novel 2-((4-((7-chloroquinolin-4 yl) amino)pentyl)((methylamino)methyl)amino) ethan-1-ol as an anti-SARS-CoV2 protease was designed through the structural modification of hydroxychloroquine. The binding energy of this drug candidate was found to be -6.9 kcal/mol. This novel drug was found to formed hydrogen and conventional interactions with the binding site of SARS-CoV2 protease through amino acids such as Glutamic acid (GLU166), Glycine (GLY143), Phenylalanine (PHE140), Asparagine (ASN142), Histidine (HIS163), His (HIS172, HIS41, HIS163), Leucine (LEU41, LEU27), Glycine (GLY143), Glutamine (GLN189), Methionine (MET49, MET165), Serine (SER 46), Cysteine (CYS145) and Threonine (THR25). With this binding energy, this new drug candidate could bind better to the human SARS-CoV2 protease’ binding site. This research provides a clue for other scientists on various ways of designing and identify the types of amino acids that may be responsible for biochemical action on SARS-CoV2 protease.

scholarly journals Potential Inhibitor of COVID-19 Main Protease (Mpro) From Several Medicinal Plant Compounds by Molecular Docking Study

2020 ◽  
Author(s):  
Siti Khaerunnisa ◽  
Hendra Kurniawan ◽  
Rizki Awaluddin ◽  
Suhartati Suhartati ◽  
Soetjipto Soetjipto
Keyword(s):  
Molecular Docking ◽  
Treatment Options ◽  
Docking Study ◽  
Binding Energies ◽  
Molecular Docking Study ◽  
Epicatechin Gallate ◽  
Discovery Studio ◽  
Main Protease ◽  
Lamarckian Genetic Algorithm ◽  
Autodock 4.2

COVID-19, a new strain of coronavirus (CoV), was identified in Wuhan, China, in 2019. No specific therapies are available and investigations regarding COVID-19 treatment are lacking. Liu et al. (2020) successfully crystallised the COVID-19 main protease (Mpro), which is a potential drug target. The present study aimed to assess bioactive compounds found in medicinal plants as potential COVID-19 Mpro inhibitors, using a molecular docking study. Molecular docking was performed using Autodock 4.2, with the Lamarckian Genetic Algorithm, to analyse the probability of docking. COVID-19 Mpro was docked with several compounds, and docking was analysed by Autodock 4.2, Pymol version 1.7.4.5 Edu, and Biovia Discovery Studio 4.5. Nelfinavir and lopinavir were used as standards for comparison. The binding energies obtained from the docking of 6LU7 with native ligand, nelfinavir, lopinavir, kaempferol, quercetin, luteolin-7-glucoside, demethoxycurcumin, naringenin, apigenin-7-glucoside, oleuropein, curcumin, catechin, epicatechin-gallate, zingerol, gingerol, and allicin were -8.37, -10.72, -9.41, -8.58, -8.47, -8.17, -7.99, -7.89, -7.83, -7.31, -7.05, -7.24, -6.67, -5.40, -5.38, and -4.03 kcal/mol, respectively. Therefore, nelfinavir and lopinavir may represent potential treatment options, and kaempferol, quercetin, luteolin-7-glucoside, demethoxycurcumin, naringenin, apigenin-7-glucoside, oleuropein, curcumin, catechin, and epicatechin-gallate appeared to have the best potential to act as COVID-19 Mpro inhibitors. However, further research is necessary to investigate their potential medicinal use.

scholarly journals Comparative Docking Analysis of Rational Drugs Against COVID-19 Main Protease

2020 ◽  
Author(s):  
LALIT SAMANT ◽  
Vyomesh Javle
Keyword(s):  
Molecular Docking ◽  
Treatment Options ◽  
Docking Study ◽  
Binding Energies ◽  
Molecular Docking Study ◽  
Docking Analysis ◽  
Discovery Studio ◽  
Main Protease ◽  
Medicinal Use ◽  
Lamarckian Genetic Algorithm

COVID-19, a new strain of coronavirus (CoV), was identified in Wuhan, China, in 2019. No specific therapies are available, and investigations regarding COVID-19 treatment are lacking. Crystallised COVID-19 main protease (Mpro), which is a potential drug target. The present study aimed to assess drugs found in literature as potential COVID-19 Mpro inhibitors, using a molecular docking study. Molecular docking was performed using Autodock 4.2, with the Lamarckian Genetic Algorithm, to analyse the probability of docking. The docking was cross-validated using Swiss Dock. COVID-19 Mpro was docked with several compounds, and docking was analysed by Biovia Discovery Studio 2020. Quinine and hydroxychloroquine were used as standards for comparison. The binding energies obtained from the docking of 6LU7, 2GTB with screened drugs viz., Quinine, Artesunate, Clotrimazol, Artemether, Quercetin, Mefloquine, ciprofloxacin, clindamycin, cipargamin, SJ-733 were in between -7.0 to -9.6 kcal/mol. On consideration of similar binding energy obtained from Autodock vina and SWISSDock and interaction residue pattern specifically (GLU 166,CYS 145, CYS44 and MET 49 residue) for SJ-733 & JPC-3210 may represent potential treatment options, and appeared to have the best potential to act as COVID-19 Mpro inhibitors. However, further research is necessary to investigate their potential medicinal use against CoV.

In silico investigation of Alliin as potential activator for AMPA receptor

2021 ◽  
Author(s):  
Hilal Ozturk ◽  
N. Yorulmaz ◽  
Mustafa Durgun ◽  
Harun Basoglu
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Ampa Receptor ◽  
Docking Study ◽  
Binding Energies ◽  
Molecular Docking Study ◽  
Gaba A ◽  
Docking Method ◽  
Ampa And Nmda Receptors ◽  
The Central Nervous System

Abstract Natural products from plants, such as flavonoids, arouse immense interest in medicine because of the therapeutic and many other bioactive properties. The molecular docking is a very useful method to screen the molecules based on their free binding energies and give important structural suggestions about how molecules might activate or inhibit the target receptor by comparing reference molecules. Alliin and Allicin differ from many other flavonoids because of containing no benzene rings and having nitrogen and sulfur atoms in their structure. In this study Alliin and Allicin affinity on AMPA, NMDA and GABA-A receptors were evaluated in the central nervous system by using the molecular docking method. Both Alliin and Allicin indicated no inhibitory effects. However Alliin showed significant selectivity to human AMPA receptor (3RN8) as an excitatory. The binding energy of glutamate to 3RN8 was -6.61 kcal/mol, while the binding energy of Allin was -8.08 kcal/mol. Furthermore Alliin’s affinity to the other AMPA and NMDA receptors is quite satisfactory compared to the reference molecule glutamate. In conclusion based on the molecular docking study, Alliin can be useful for synaptic plasticity studies whereas might be enhance seizure activity because of the increased permeability to cations. It also can be beneficial to improve learning and memory and can be used as a supportive product to the hypofunction of NMDA associated problems.

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