scholarly journals STUDI IN SILICO SIFAT FARMAKOKINETIK, TOKSISITAS, DAN AKTIVITAS IMUNOMODULATOR BRAZILEIN KAYU SECANG TERHADAP ENZIM 3-CHYMOTRYPSIN-LIKE CYSTEINE PROTEASE CORONAVIRUS

2020 ◽  
Vol 1 (1) ◽  
pp. 76-85
Author(s):  
Dwi Krihariyani Dwi ◽  
Retno Sasongkowati ◽  
Edy Haryanto
Keyword(s):  
Cysteine Protease ◽  
In Silico ◽  
Online Tool ◽  
Molegro Virtual Docker

Enzim 3-chymotrypsin-like cysteine protease (3CLpro) adalah enzim yang berfungsi  mengendalikan replikasi dalam siklus hidup coronavirus. Enzim 3CLproadalah target biologis (reseptor) yang akan berinteraksi dengan obat (ligan). Brazilein merupakan kandungan senyawa mayor dalam kayu secang yang secara empiris digunakan sebagai imunomodulator. Penelitian ini bertujuan untuk memprediksi secara in silico aktivitas imunomodulator senyawa brazilein terhadap enzim 3CLpro, dengan senyawa pembanding kurkumin. Uji in silico digunakan untuk memprediksi aktivitas imunomodulator dengan melakukan docking menggunakan program komputer Molegro Virtual Docker. Reseptor yang digunakan adalah 3CLpro, kode PDB: 6M2N, dengan ligan 3WL_401[C]. Prediksi sifat farmakokinetik (ADME) dan toksisitas brazilein dan kurkumin dilakukan menggunakan program pkCSM online tool. Analisis data dilakukan dengan membandingkan energi ikatan hasil docking antara brazilein, ligan, dan kurkumin pada reseptor target. Semakin rendah energi ikatan ligan dengan reseptor target, semakin stabil ikatan yang terbentuk. Hasil uji in silico menunjukkan bahwa energi ikatan ligan = -83.1153kkal/mol, brazilein = -82.0583kkal/mol, dan kurkumin = -115.852kkal/mol. Hasil uji di atas menunjukkan bahwa brazilein memiliki potensi sebagai imunomodulator meskipun lebih rendah dibanding ligan dan kurkumin. Hasil uji in silico menggunakan program pkCSM online tool menunjukkan bahwa senyawa brazilein mempunyai sifat farmakokinetik yang baik, dan menimbulkan toksisitas yang relatif rendah.

scholarly journals In Silico Analysis of Antiviral Activity and Pharmacokinetic Prediction of Brazilein Sappan Wood (Caesalpinia sappan L.) Against SARS-CoV-2 Spike Glycoproteins

2021 ◽  
Vol 3 (1) ◽  
pp. 26-37
Author(s):  
Dwi Krihariyani ◽  
Edy Haryanto ◽  
Retno Sasongkowati
Keyword(s):  
Vitamin C ◽  
Antiviral Activity ◽  
Bond Energy ◽  
In Silico ◽  
In Silico Analysis ◽  
Data Bank ◽  
Online Tool ◽  
Molegro Virtual Docker ◽  
Pharmacokinetic Properties ◽  
Low Toxicity

Brazilein is one of the secondary sappan wood metabolites which can be used empirically as an antivirus. The SARS-CoV-2 spike (S) glycoproteins play significant roles in attaching and entering the virus into the host cell. This study aims to predict the antiviral activity and pharmacokinetic properties of brazilein of the sappan wood against the in-silico SARS-CoV-2 S glycoproteins with vitamin C as the reference compound. Molegro Virtual Docker 5.5 was used to predict antiviral activity by docking process. SARS-CoV-2 S glycoprotein with NAG ligand available in Protein Data Bank (PDB) (PDB ID: 7C01) was the receptor used. The pkCSM online tool was used to predict the pharmacokinetic properties and toxicity of brazilein. Data were analyzed on the target receptors by comparing the docking bond energies between NAG, brazilein, and vitamin C. The smaller the ligands’ bond energy to the target receptor, the more stable the bonds are. The bond energy of NAG, brazilein, and vitamin C was -59.2864 kcal/mol, -65.8911 kcal/mol, and -53.9093 kcal/mol, respectively. These results suggested that brazilein has a greater capacity as an antivirus compared to NAG and vitamin C. In silico test using the pkCSM online tool demonstrated that brazilein had strong pharmacokinetic properties and relatively low 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 Cruzain structures: apocruzain and cruzain bound to S-methyl thiomethanesulfonate and implications for drug design

2019 ◽  
Vol 75 (6) ◽  
pp. 419-427 ◽  
Author(s):  
Elany Barbosa da Silva ◽  
Elfriede Dall ◽  
Peter Briza ◽  
Hans Brandstetter ◽  
Rafaela Salgado Ferreira
Keyword(s):  
Drug Design ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Cysteine Protease ◽  
In Silico ◽  
Structural Information ◽  
Mass Spectrometric ◽  
Catalytic Cysteine ◽  
Reversible Covalent ◽  
Covalent Inhibitor

Chagas disease, which is caused by Trypanosoma cruzi, affects more than six million people worldwide. Cruzain is the major cysteine protease involved in the survival of this parasite. Here, the expression, purification and crystallization of this enzyme are reported. The cruzain crystals diffracted to 1.2 Å resolution, yielding two novel cruzain structures: apocruzain and cruzain bound to the reversible covalent inhibitor S-methyl thiomethanesulfonate. Mass-spectrometric experiments confirmed the presence of a methylthiol group attached to the catalytic cysteine. Comparison of these structures with previously published structures indicates the rigidity of the cruzain structure. These results provide further structural information about the enzyme and may help in new in silico studies to identify or optimize novel prototypes of cruzain inhibitors.

scholarly journals In Silico Study of 1,5-Bis(4-Hydroxy-3-Methoxyphenyl)-1,4-Pentadiene-3-One (Deketene Curcumin) on Crystallized Protein Structures of SARS-CoV-2

2020 ◽  
Author(s):  
Vraj shah ◽  
Jaydip Bhaliya ◽  
Dhwani Shah
Keyword(s):  
In Silico ◽  
Low Cost ◽  
Protein Structures ◽  
Antiviral Drug ◽  
Good Choice ◽  
World Health ◽  
Effective Vaccine ◽  
Steric Interaction ◽  
Molegro Virtual Docker ◽  
In Silico Study

<p>World Health Organization (WHO) reveals total number of coronavirus cases are 5,684,802 and 352,225 deaths till today worldwide. Coronavirus instances are nevertheless surging due to its speedy spreading through infected patients. Therefore, in order to find potent vaccine almost every researcher is doing hard work to find it. However, until today there is not any availability of effective vaccine or drug for the treatment of COVID-19. In this case, the computational approach is the good choice to identify effective drugs and could be very useful due to its low cost, less error and less time consumption. Here, Deketene curcumin has taken for docking study because of its lots of biological applications such as antiviral, antimicrobial, anti-inflammatory, antioxidant, antibiotic, and to a name of few, it is a derivative of curcumin. In this study, five main protease crystallized COVID-19 structures (PDB ID: 6LU7, 5R7Z, 5R7Y, 5R80, 5R81) have been taken for simulation against deketene curcumin. Required procedure for this in silico study done through Molegro virtual docker (MVD) and Molegro Molecular Viewer (MMV) used for visualization. The results showed H-bonding and steric interaction between Deketene Curcumin with COVID-19 (PDB ID: 6LU7, 5R7Z, 5R7Y, 5R80, 5R81). Moldock scores of Deketene Curcumin Observed -134.198 kcal/mol, -151.972 kcal/mol, -109.224 kcal/mol, -140.741 kcal/mol and -126.562 kcal/mol with PDB Id 6LU7, 5R7Z, 5R7Y, 5R80 and 5R81 respectively. As per our results, it can be say that Deketene Curcumin has effective as a lead compound to find new antiviral drug candidates against COVID-19 for possible medicinal agent.</p>

In silico study examining new phenylpropanoids targets with antidepressant activity

2020 ◽  
Vol 21 ◽  
Author(s):  
Luciana Scotti ◽  
Poliane da Silva Calixto ◽  
Mirian G. S. Stiebbe Salvadori ◽  
Reinaldo Nóbrega de Almeida ◽  
Mayara dos Santos Maia ◽  
...  
Keyword(s):  
In Silico ◽  
Late Onset ◽  
Clinical Psychopharmacology ◽  
Three Dimensional ◽  
Public Health Problem ◽  
Antidepressant Activity ◽  
Docking Studies ◽  
Dimensional Structure ◽  
Molegro Virtual Docker ◽  
Stereochemical Quality

Background: Natural products, such as phenylpropanoids, which are found in essential oils derived from aromatic plants, have been explored during non-clinical psychopharmacology studies, to discover new molecules with relevant pharmacological activities in the central nervous system, especially antidepressant and anxiolytic activities. Major depressive disorder is a highly debilitating psychiatric disorder and is considered to be a disabling public health problem, worldwide, as a primary factor associated with suicide. Current clinically administered antidepressants have late-onset therapeutic actions, are associated with several side effects, and clinical studies have reported that some patients do not respond well to treatment or reach complete remission. Objective: To review important new targets for antidepressant activity and to select phenylpropanoids with antidepressant activity, using Molegro Virtual Docker and Ossis Data Warris, and to verify substances with more promising antidepressant activity. Results and Conclusion: We conducted an in silico molecular modeling study, based on homology, to determine the three-dimensional structure the 5-hydroxytryptamine 2A receptor (5-HT2AR), then performed molecular docking studies and examined the predisposition for cytotoxicity risk among identified molecules. We obtained a model for 5-HT2AR homology, with satisfactory results, indicating the good stereochemical quality of the model. The phenylpropanoid 4- allyl-2,6-dimethoxyphenol showed the lowest binding energy for 5-HT2AR, with results relevant to the L-arginine/nitric oxide (NO)/cGMP pathway, and showed no toxicity within the parameters of mutagenicity, carcinogenicity, reproductive system toxicity, and skin-tissue irritability, when evaluated in silico; therefore, this molecule can be considered promising for the investigation of antidepressant activity.

STUDI IN SILICO DAN HUBUNGAN KUANTITATIF STRUKTUR TERHADAP AKTIVITAS TANAMAN MANGROVE (Avicennia marina (Forssk.) Vierh.) SEBAGAI ANTIDIABETES

2020 ◽  
Vol 2 (1) ◽  
pp. 112
Author(s):  
Arinil Hidayati ◽  
Siswandono Siswandono ◽  
Pramudita Riwanti
Keyword(s):  
Regression Analysis ◽  
In Silico ◽  
Avicennia Marina ◽  
Three Dimensions ◽  
Peroxisome Proliferator ◽  
Nonlinear Relationship ◽  
Peroxisome Proliferator Activated Receptor ◽  
Molegro Virtual Docker ◽  
Relationship Of

The research is applied to 20 compounds contained  into <em>Avicennia marina</em> which is : <em>4’,5-dihydroxy-3’,5’,7-trimethoxyflavone, isorhamnetin 3-O-rutinoside, quercetin, stenocarproquinone B, avicennone C, avicennone E, avicennone F, avicennone D,   4’,5-dihydroxy-3’,7-dimethoxyflavone, chrysoeriol 7-O-glucoside, naphta(1,2-b)furan-4,5-dione, 3-hydroxy-naphta(1,2-b)furan-4,5-dione, kaempferol, 5-hydroxy-4’,7-dimethoxyflavone, avicequinone C, 2-[2’-(2’-hydroxy)propyl]-naphta[1,2-b]furan-4,5-dione, 4’,5,7-trihydroxyflavone, luteolin 7-O-methylether, luteolin 7-O-methylether 3’-O-beta-D-glucoside, 5,7-dihydroxy-3’,4’,5’-trimethoxyflavone</em> which are expected  to have an  effect as antidiabetics agent. It is undertaken to find out the linier or nonlinier relationship of  the structure activty (QSAR), the physicochemical characters (lipophilic, electronic, dan steric) to the activity changing (<em>rerank score</em>). Moreover, it is also undertaken to find out which one of those 20 <em>Avicennia marina </em>compounds are predicted to possess the activity as the best antidiabetics agent by the comparison of pioglitazon. It is arranged through computerized methods or <em>in silico</em> not only for having  the structure of two and three dimensions but also knowing the physicochemical characters too; through some programs such as  <em>ChemBioDraw Ultra </em>12.0 and <em>ChemBio3D Ultra </em>12.0 from <em>CambridgeSoft. The docking </em>program is used to make prediction of  the activity  by using <em>Molegro Virtual  Docker </em>2011.5.0.0 from CLCBio<em>.</em> by using the <em>peroxisome proliferator-activated receptor-gamma </em>(PPAR𝛾) in code of PDB: 2XKW. The result of the regression analysis through IBM SPSS program shows nonlinear relationship among structures, <em>Avicennia marina</em> physicochemical characters of twenty compound contents dealing with the activity changing. The compound of  <em>isorhamnetin 3-O-rutinoside</em><em>, chrysoeriol 7-O-glucoside, </em>and <em>luteolin 7-O-methylether 3’-O-beta-D-glucoside </em>are predicted to have the best antidiabetics agent if it is compared with the comparing drug pioglitazon.

scholarly journals In-silico studies of HMG-Co A reductase inhibitors present in fruits of Withania coagulans Dunal (Solanaceae)

2020 ◽  
Vol 19 (2) ◽  
pp. 305-312
Author(s):  
Tooba Lateef ◽  
Sadaf Naeem ◽  
Shamim A. Qureshi
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
In Silico ◽  
Chemical Constituents ◽  
Hmg Coa Reductase ◽  
Docking Score ◽  
Molegro Virtual Docker ◽  
Withania Coagulans ◽  
Artery Disease ◽  
Coa Reductase

Purpose: To evaluate the antihypercholesterolemic effect of chemical constituents of W. coagulans by determining inhibitory effect of the compounds against HMG-CoA reductase, using in-silico methods. Method: Docking simulations of twenty-one chemical constituents, found in the fruits of W. coagulans were performed against HMGCR(PDB ID: 2Q1L) using Molegro Virtual Docker software. The best docked poses were then selected, based on the docking score and amino acids involved in the interaction within the ligand and active site of protein. Results: Five compounds viz. Coagulin D (comp no. 11), Ergosta-5,25-diene-3β,24ε-diol (comp no. 13), Withacoagulin (comp no. 15), and Withaferin (comp no. 16), showed the highest MolDock scores. These compounds with highest docking score, also formed hydrogen bond interactions with His (752), Lys (692, 735), Asp (690), Glu (559) within the binding site of HMG-CoA reductase, thus, halting enzyme activity. Whereas, Withanolide D (comp no. 17) with high MolDock score did not show hydrogen bonding interactions. Conclusion: The high MolDock score and maximum binding with catalytic region of the enzyme indicate that compounds selected from the fruits of W. coagulans are potential blockers of HMG-CoA reductase. Thus, the compounds may be useful for the management of hypercholesterolemia, which untreated, often leads to coronary artery disease. Keywords: Withania coagulans, Coronary artery disease, HMG-CoA reductase, Molegro virtual docker, Hypercholesterolemia, In silico studies

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