scholarly journals Discovery of Potential Plant-derived Iradoides with COVID-19 Mpro in silico

2021 ◽  
Author(s):  
Mohd Rehan
Keyword(s):  
Natural Products ◽  
Chinese Medicine ◽  
In Silico ◽  
Binding Energies ◽  
Small Class ◽  
Chinese Scientist ◽  
Autodock Vina ◽  
Discovery Studio ◽  
Traditional System ◽  
Potential Target

Abstract Iradoides are a small class of plant derived natural products, which used in traditional system of medicine such as Unani, Tibetan, Ayurveda, Siddha, and Chinese medicine. The several diverse types of iradoides have been isolated from many parts of the plant such as root, leaves, flowers, stem, rhizomes, bark, and seed. Here, we used bioactive iradoides to know the potency against COVID-19 Mpro. The COVID-19 Mpro is a potential target of the drug, which identified by Chinese scientist (published manuscript in Nature on June 2020). From several studies, we found that many natural products such as flavonoids, saponins, steroids, terpenoids, and synthesized compounds have been used on this target (COVID-19 Mpro). We screened a series of iradoides against COVID-19 Mpro (PDB ID: 6LU7) by using many docking software as BIOVIA Discovery Studio 2017 R2, Chimera 1.13.1, Auto Dock Tools-1.5.6, AutoDock Vina to known best inhibitor against COVID-19 Mpro. According to obtained results, 6′-O-trans-feruloylnegundoside, p-hydroxybenzoyl-6′-O-trans-caffeoylgardoside, 2′-O-p-hydroxybenzoyl gardoside, 6-deoxyharpagide, reptoside show binding energies -8.1, -8.3, -8.2, -7.0, and -7.1 Kcal/mol, respectively. From this study, we found that all iradoides show more potency on COVID-19 Mpro when compared with Chloroquine and hydroxychloroquine. The Chloroquine and hydroxychloroquine used as standards for comparison. From the results of this study, we found that iradoides may be useful in the treatment of COVID-19 patients.

scholarly journals THE POTENTIAL OF ROBUSTA COFFEE (COFFEA CANEPHORA) AS A COLORECTAL CANCER THERAPY MODALITY: AN IN SILICO STUDY

2021 ◽  
pp. 83-87
Author(s):  
DESSY AGUSTINI ◽  
LEO VERNADESLY ◽  
DELVIANA ◽  
THEODORUS
Keyword(s):  
Colorectal Cancer ◽  
In Silico ◽  
Hydrophobic Interactions ◽  
Binding Energies ◽  
In Vivo Studies ◽  
Discovery Studio ◽  
Robusta Coffee ◽  
In Silico Study

Objectives: This research aims to determine the efficacy of compounds in robusta coffee against colorectal cancer through the inhibition of the T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) receptor. Methods: This in silico study has been conducted in computing platform from June to August 2021. The selected test compounds would go through the Lipinski rule screening through the SwissADME website and the compounds that met these regulations would be docked to the TIGIT protein using AutoDock Tools and AutoDock Vina. The interactions with the highest binding energies were visualized using BIOVIA Discovery Studio 2020. The test compounds then underwent a toxicity profile analysis on the admetSAR 2.0 website. Results: All test compounds complied with the Lipinski rule. The molecular docking results showed the highest binding energy in kahweol and cafestol (−8.1 kcal/mol) compared to OMC (−7.9 kcal/mol), chlorogenic acid (−7.8 kcal/mol), caffeic acid (−6.3 kcal/mol), caffeine (−6.1 kcal/mol), trigonelline (−5.3 kcal/mol), HMF (−5.1 kcal/mol), furfuryl alcohol (−4.4 kcal/mol), and 5-fluorouracil as the comparator drug (−5.3 kcal/mol). Kahweol, cafestol, and 5-fluorouracil revealed the hydrophobic interactions and hydrogen bonds with amino acid residues in TIGIT. Kahweol and cafestol unveiled minimal toxicity prediction Conclusion: Kahweol and cafestol demonstrated the best results in inhibiting the TIGIT protein which played a role in colorectal cancer. In vitro and in vivo studies are needed to strengthen the findings of this research.

scholarly journals Flavonoides das plantas do gênero Lavandula como potenciais inibidores de proteínas-chave do SARS-CoV-2

2021 ◽  
Vol 10 (12) ◽  
pp. e345101220580
Author(s):  
José Gabriel Fontenele Gomes ◽  
Neirigelson Ferreira de Barros Leite
Keyword(s):  
In Silico ◽  
Autodock Vina ◽  
Discovery Studio

Objetivo: avaliar o perfil de interações entre os flavonoides frente às proteínas-chave da infecção pelo SARS-CoV-2, e de modo secundário, objetivou-se analisar as propriedades destes constituintes químicos frente à Regra de Lipinski como potenciais candidatos a fármacos. Metodologia: Este estudo caracteriza-se como do tipo quantitativo descritivo de caráter experimental, através de métodos computacionais, onde foram utilizados os programas AutoDock Tools, AutoDock  Vina, Biovia Discovery Studio e ChimeraX para a realização do acoplamento molecular entre os principais flavonoides presentes nas plantas do gênero Lavandula com a proteína M e o complexo entre a Enzima Conversora de Angiotensina 2 e o domínio de ligação do receptor da proteína S do SARS-CoV-2. Resultados: Analisando-se as interações isoladas de cada flavonoide com as proteínas, nota-se que os compostos apresentaram interações mais favoráveis com a Enzima Conversora de Angiotensina 2 e o domínio de ligação do receptor. Para a regra de Lipinski, a Delfinidina apresentou duas violações, sendo considerada, neste contexto, uma molécula pouco promissora. Conclusão: Conclui-se, portanto, que os flavonoides apresentam in silico um potencial inibitório para as proteínas testadas, sendo mais favorável ao complexo da Enzima Conversora de Angiotensina 2 com o domínio de ligação ao receptor. Frente à regra de Lipinski, apenas a Delfinidina demonstrou baixo potencial para candidata a fármaco, contudo, o uso de nanocarreadores poderia contornar algumas de suas limitações.

scholarly journals Targeting Omp-A Protein of Acinetobacter Baumannii with the Bio-Active Compounds from Azadirachta Indica - an in-silico Approach

2021 ◽  
pp. 323-334
Author(s):  
R. Nandita ◽  
A. S. Smiline Girija ◽  
P. Sankar Ganesh ◽  
J. Vijayashree Priyadharsini
Keyword(s):  
Crystal Structure ◽  
Acinetobacter Baumannii ◽  
Azadirachta Indica ◽  
In Silico ◽  
3D Structure ◽  
Data Bank ◽  
Binding Energies ◽  
Active Compounds ◽  
Discovery Studio ◽  
Ompa Protein

Background: Acinetobacter baumannii is a gram negative bacterium which is typically short, round, coccobacillus and was named after the bacteriologist Paul Baumann. It is an emerging dental pathogen since it acquires  drug resistance and expression of several virulence genes. It is an opportunistic pathogen in humans, affecting people with compromised immune systems. Acinetobacter baumannii is an arising nosocomial microorganism causing serious complications because of the propensity of its multi-drug resistant property. Aim: The aim of the present study was to target omp-A protein of Acinetobacter baumannii with the bio active compounds from Azadirachta indica an in-silico approach. Materials and Methods: The crystal structure of ompA protein was obtained from the PDB protein data bank. The structures of the bio-active derivatives of A. indica were obtained from the chemsketch software. The generated 3D structures were then optimised. Auto Dock instrument was utilized for docking investigation to interpret the affinity between bio-compounds of A. indica against ompA protein of A. baumannii. Results: The 3D crystal structure of OmpA-like domain from A.baumannii was retrieved from PDB database and its PDB ID was 3TD3 – A chain. 3D Structure of OmpA visualization using Biovia-Discovery studio visualizer. The 2D structure of compounds from Azadirachta indica was drawn using ACD chemsketch and saved in MDL-mol format and converted to PDB format using open babel converter. The final docked structures for the drug ligand interactions were assessed for their binding energies and hydrogen bonds. Conclusion: The present study had achieved the anti-biofilm inhibitory effect of imidazole-2-carboxylic acid from A. indica exhibiting a great interaction between activity with ompA utilizing computational investigation.

scholarly journals Computational Studies Applied to Flavonoids against Alzheimer’s and Parkinson’s Diseases

2018 ◽  
Vol 2018 ◽  
pp. 1-21 ◽  
Author(s):  
Alex France M. Monteiro ◽  
Jéssika De O. Viana ◽  
Anuraj Nayarisseri ◽  
Ernestine N. Zondegoumba ◽  
Francisco Jaime B. Mendonça Junior ◽  
...  
Keyword(s):  
Natural Products ◽  
Molecular Docking ◽  
Neurodegenerative Diseases ◽  
In Silico ◽  
Docking Studies ◽  
Binding Energies ◽  
Computational Studies ◽  
Epicatechin Gallate ◽  
Drug Candidates ◽  
Parkinson’S Diseases

Neurodegenerative diseases, such as Parkinson’s and Alzheimer’s, are understood as occurring through genetic, cellular, and multifactor pathophysiological mechanisms. Several natural products such as flavonoids have been reported in the literature for having the capacity to cross the blood-brain barrier and slow the progression of such diseases. The present article reports on in silico enzymatic target studies and natural products as inhibitors for the treatment of Parkinson’s and Alzheimer’s diseases. In this study we evaluated 39 flavonoids using prediction of molecular properties and in silico docking studies, while comparing against 7 standard reference compounds: 4 for Parkinson’s and 3 for Alzheimer’s. Osiris analysis revealed that most of the flavonoids presented no toxicity and good absorption parameters. The Parkinson’s docking results using selected flavonoids as compared to the standards with four proteins revealed similar binding energies, indicating that the compounds 8-prenylnaringenin, europinidin, epicatechin gallate, homoeriodictyol, capensinidin, and rosinidin are potential leads with the necessary pharmacological and structural properties to be drug candidates. The Alzheimer’s docking results suggested that seven of the 39 flavonoids studied, being those with the best molecular docking results, presenting no toxicity risks, and having good absorption rates (8-prenylnaringenin, europinidin, epicatechin gallate, homoeriodictyol, aspalathin, butin, and norartocarpetin) for the targets analyzed, are the flavonoids which possess the most adequate pharmacological profiles.

scholarly journals In Silico Approaches to Identify Polyphenol Compounds as α-Glucosidase and α-Amylase Inhibitors against Type-II Diabetes

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1877
Author(s):  
Jirawat Riyaphan ◽  
Dinh-Chuong Pham ◽  
Max K. Leong ◽  
Ching-Feng Weng
Keyword(s):  
Natural Products ◽  
In Silico ◽  
Type Ii Diabetes ◽  
Postprandial Glucose ◽  
Type Ii Diabetes Mellitus ◽  
Type Ii ◽  
Amino Acid Residues ◽  
Discovery Studio

Type-II diabetes mellitus (T2DM) results from a combination of genetic and lifestyle factors, and the prevalence of T2DM is increasing worldwide. Clinically, both α-glucosidase and α-amylase enzymes inhibitors can suppress peaks of postprandial glucose with surplus adverse effects, leading to efforts devoted to urgently seeking new anti-diabetes drugs from natural sources for delayed starch digestion. This review attempts to explore 10 families e.g., Bignoniaceae, Ericaceae, Dryopteridaceae, Campanulaceae, Geraniaceae, Euphorbiaceae, Rubiaceae, Acanthaceae, Rutaceae, and Moraceae as medicinal plants, and folk and herb medicines for lowering blood glucose level, or alternative anti-diabetic natural products. Many natural products have been studied in silico, in vitro, and in vivo assays to restrain hyperglycemia. In addition, natural products, and particularly polyphenols, possess diverse structures for exploring them as inhibitors of α-glucosidase and α-amylase. Interestingly, an in silico discovery approach using natural compounds via virtual screening could directly target α-glucosidase and α-amylase enzymes through Monte Carto molecular modeling. Autodock, MOE-Dock, Biovia Discovery Studio, PyMOL, and Accelrys have been used to discover new candidates as inhibitors or activators. While docking score, binding energy (Kcal/mol), the number of hydrogen bonds, or interactions with critical amino acid residues have been taken into concerning the reliability of software for validation of enzymatic analysis, in vitro cell assay and in vivo animal tests are required to obtain leads, hits, and candidates in drug discovery and development.

scholarly journals Ácido Valerênico e seu potencial ansiolítico por meio da interação com receptores do tipo GABAA: um estudo in silico

2021 ◽  
Vol 10 (13) ◽  
pp. e07101320677
Author(s):  
José Gabriel Fontenele Gomes ◽  
Liliam With Monalisa Araujo Silva ◽  
Weslley Tiago Bitencourt de Andrade ◽  
Anne Karolinne Melo de Andrade Gomes ◽  
Clara Rita de Sousa Magalhães ◽  
...  
Keyword(s):  
In Silico ◽  
Autodock Vina ◽  
Discovery Studio ◽  
De Se

Objetivo: Analisar o potencial ansiolítico do Ácido Valerênico mediante o acoplamento molecular in silico em receptores do tipo GABAA. Metodologia: Realizou-se um estudo do tipo quantitativo descritivo, com caráter experimental. A fim de se confirmar a validade da metodologia durante o acoplamento molecular, realizou-se um redocking utilizando a molécula de Diazepam nativa cristalografada com o receptor GABAA. As interações já apresentadas pelo Diazepam com o receptor, foram utilizadas para fins comparativos com as interações do Ácido Valerênico. As estruturas dos compostos foram obtidas por meio da plataforma PubChem. Para a representação tridimensional das estruturas foi utilizado o programa ChimeraX. Para a realização de todo o procedimento de docking foram utilizados os programas Biovia Discovery Studio, Avogadro, AutoDock Tools e AutoDock Vina. Resultados: Constatou-se que dentre todos os valores de afinidade demonstrados, levando-se em conta sua eletronegatividade, o Ácido Valerênico foi quem apresentou menor gasto energético. Nota-se também que o composto em questão viola apenas o parâmetro do LogP, o que o configura como um bom candidato a possível novo fármaco. Conclusão: Através do estudo in silico, foi possível a análise do potencial ansiolítico do Ácido Valerênico. Por meio da utilização do Diazepam e suas interações com o receptor GABAA como parâmetro, foi possível identificar que o Ácido Valerênico apresenta interações com gasto energético mínimo, e consequentemente valores aceitáveis de afinidade.

Role of 4-O Galloylchlorogenic Acid in Lung Cancer- An Insilico Approach

2017 ◽  
Vol 9 (5) ◽  
Author(s):  
Jaynthy C. ◽  
N. Premjanu ◽  
Abhinav Srivastava
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
In Silico ◽  
Computational Study ◽  
Regulation Mechanism ◽  
Down Regulation ◽  
Fruit Extract ◽  
In Vitro Techniques ◽  
Discovery Studio

Cancer is a major disease with millions of patients diagnosed each year with high mortality around the world. Various studies are still going on to study the further mechanisms and pathways of the cancer cell proliferation. Fucosylation is one of the most important oligosaccharide modifications involved in cancer and inflammation. In cancer development increased core fucosylation by FUT8 play an important role in cell proliferation. Down regulation of FUT8 expression may help cure lung cancer. Therefore the computational study based on the down regulation mechanism of FUT8 was mechanised. Sapota fruit extract, containing 4-Ogalloylchlorogenic acid was used as the inhibitor against FUT-8 as target and docking was performed using in-silico tool, Accelrys Discovery Studio. There were several conformations of the docked result, and conformation 1 showed 80% dock score between the ligand and the target. Further the amino acids of the inhibitor involved in docking were studied using another tool, Ligplot. Thus, in-silico analysis based on drug designing parameters shows that the fruit extract can be studied further using in-vitro techniques to know its pharmacokinetics.

In Silico Molecular Docking and Molecular Dynamic Simulation of Potential Inhibitors of 3C-like Main Proteinase (3CLpro) from Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Using Selected African Medicinal Plants

2020 ◽  
Author(s):  
Sahar Qazi ◽  
Mustafa Alhaji Isa ◽  
Adam Mustapha ◽  
Khalid Raza ◽  
Ibrahim Alkali Allamin ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Severe Acute Respiratory Syndrome ◽  
In Silico ◽  
Md Simulation ◽  
Binding Energies ◽  
Anacardium Occidentale ◽  
Upper Respiratory Tract ◽  
Ligand Complex ◽  
In Silico Docking ◽  
Main Protease

<p>The Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) is an infectious virus that causes mild to severe life-threatening upper respiratory tract infection. The virus emerged in Wuhan, China in 2019, and later spread across the globe. Its genome has been completely sequenced and based on the genomic information, the virus possessed 3C-Like Main Protease (3CLpro), an essential multifunctional enzyme that plays a vital role in the replication and transcription of the virus by cleaving polyprotein at eleven various sites to produce different non-structural proteins. This makes the protein an important target for drug design and discovery. Herein, we analyzed the interaction between the 3CLpro and potential inhibitory compounds identified from the extracts of <i>Zingiber offinale</i> and <i>Anacardium occidentale</i> using in silico docking and Molecular Dynamics (MD) Simulation. The crystal structure of SARS-CoV-2 main protease in complex with 02J (5-Methylisoxazole-3-carboxylic acid) and PEJ (composite ligand) (PDB Code: 6LU7,2.16Å) retrieved from Protein Data Bank (PDB) and subject to structure optimization and energy minimization. A total of twenty-nine compounds were obtained from the extracts of <i>Zingiber offinale </i>and the leaves of <i>Anacardium occidentale. </i>These compounds were screened for physicochemical (Lipinski rule of five, Veber rule, and Egan filter), <i>Pan</i>-Assay Interference Structure (PAINS), and pharmacokinetic properties to determine the Pharmaceutical Active Ingredients (PAIs). Of the 29 compounds, only nineteen (19) possessed drug-likeness properties with efficient oral bioavailability and less toxicity. These compounds subjected to molecular docking analysis to determine their binding energies with the 3CLpro. The result of the analysis indicated that the free binding energies of the compounds ranged between ˗5.08 and -10.24kcal/mol, better than the binding energies of 02j (-4.10kcal/mol) and PJE (-5.07kcal.mol). Six compounds (CID_99615 = -10.24kcal/mol, CID_3981360 = 9.75kcal/mol, CID_9910474 = -9.14kcal/mol, CID_11697907 = -9.10kcal/mol, CID_10503282 = -9.09kcal/mol and CID_620012 = -8.53kcal/mol) with good binding energies further selected and subjected to MD Simulation to determine the stability of the protein-ligand complex. The results of the analysis indicated that all the ligands form stable complexes with the protein, although, CID_9910474 and CID_10503282 had a better stability when compared to other selected phytochemicals (CID_99615, CID_3981360, CID_620012, and CID_11697907). </p>

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