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 Evaluation of N-benzoylthiourea derivatives as popssible analgesic agents by predicting their hysicochemical and pharmacokinetic properties, toxicity, and analgesic activity

2018 ◽  
Vol 22 (2) ◽  
pp. 76
Author(s):  
Suko Hardjono ◽  
Siswandono Siswandono ◽  
Rina Andayani
Keyword(s):  
Physicochemical Properties ◽  
Analgesic Activity ◽  
Analgesic Drugs ◽  
Molegro Virtual Docker ◽  
Online Tools ◽  
Pharmacokinetic Properties ◽  
Analgesic Agents ◽  
Reference Ligand ◽  
Low Toxicity ◽  
Cox 2

This study aimed to predict the physicochemical properties, pharmacokinetic properties (ADME), toxicity, and analgesic activity of 30 compounds of N-benzoylthiourea derivatives that are potential analgesic drugs. One of the mechanisms of action of N-benzoylthiourea derivatives is the inhibition of the cyclooxygenase-2 (COX-2) isoenzyme. An in silico test was performed by docking a compound that would predict its activity with the target COX-2 isoenzyme, PDB ID: 1PXX, using the MVD (Molegro Virtual Docker) program. The result of the docking was a form of energy bond indicated by the value of the rerank score (RS), where compounds that had lower RS values were predicted to have a higher activity. The pkCSM and Protox online tools were used to predict various physicochemical properties. Based on the RS values, the N-benzoylthiourea derivatives can be predicted to have lower analgesic activity than diclofenac, the reference ligand. Three of the N-benzoylthiourea derivatives—N-(2,4-bis-trifluoromethyl)-benzoylthiourea, N-(3,5-bis-trifluoromethyl)benzoylthiourea, and N-(3-trifluoromethoxy)-benzoylthiourea—had RS values of -90.82, -94.73, and -92.76,  respectively, suggesting that these compounds were predicted to have analgesic activity relatively similar to diclofenac (RS value = -95.16). Furthermore, the majority of the  N-benzoylthiourea derivatives were predicted to have good pharmacokinetic properties (ADME), and cause relatively low toxicity.

scholarly journals Ribavirin shows antiviral activity against SARS-CoV-2 and downregulates the activity of TMPRSS2 and the expression of ACE2 in vitro

2021 ◽  
pp. 1-12 ◽  
Author(s):  
Mehmet Altay Unal ◽  
Ceylan Verda Bitirim ◽  
Gokce Yagmur Summak ◽  
Sidar Bereketoglu ◽  
Inci Cevher Zeytin ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Broad Spectrum ◽  
In Silico ◽  
Antiviral Drug ◽  
In Silico Analysis ◽  
Cell Types ◽  
Suppressive Effect ◽  
Inhibitory Effect ◽  
Molecular Techniques

Ribavirin is a guanosine analog with broad-spectrum antiviral activity against RNA viruses. Based on this, we aimed to show the anti-SARS-CoV-2 activity of this drug molecule via in vitro, in silico, and molecular techniques. Ribavirin showed antiviral activity in Vero E6 cells following SARS-CoV-2 infection, whereas the drug itself did not show any toxic effect over the concentration range tested. In silico analysis suggested that ribavirin has a broad-spectrum impact on SARS-CoV-2, acting at different viral proteins. According to the detailed molecular techniques, ribavirin was shown to decrease the expression of TMPRSS2 at both mRNA and protein levels 48 h after treatment. The suppressive effect of ribavirin in ACE2 protein expression was shown to be dependent on cell types. Finally, proteolytic activity assays showed that ribavirin also showed an inhibitory effect on the TMPRSS2 enzyme. Based on these results, we hypothesized that ribavirin may inhibit the expression of TMPRSS2 by modulating the formation of inhibitory G-quadruplex structures at the TMPRSS2 promoter. As a conclusion, ribavirin is a potential antiviral drug for the treatment against SARS-CoV-2, and it interferes with the effects of TMPRSS2 and ACE2 expression.

scholarly journals Penambatan In Siliko Senyawa Ester Naringenin Sebagai Antidiabetes

2018 ◽  
Vol 1 (1) ◽  
pp. 245-250
Author(s):  
Nerdy Nerdy ◽  
Effendy De Lux Putra ◽  
Ginda Haro ◽  
Urip Harahap
Keyword(s):  
Diabetes Mellitus ◽  
Protein Data Bank ◽  
Bond Energy ◽  
In Silico ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Parent Compound ◽  
Data Bank ◽  
Mean Square ◽  
In Silico Docking ◽  
Diabetes Melitus

Diabetes melitus merupakan penyakit yang diderita oleh banyak orang di dunia. Banyak obat sintetik yang tersedia untuk pengobatan diabetes melitus. Namun, ada kebutuhan yang mendesak untuk menghasilkan obat antidiabetes yang lebih baik khususnya dari bahan alam. Literatur menunjukkan bahwa flavonoid merupakan metabolit sekunder dari tumbuhan yang berkhasiat sebagai antidiabetes yang baik. Naringenin merupakan flavonoid dari jeruk yang memiliki aktivitas antidiabetes. Senyawa turunan lipofilik dari flavonoid naringenin yang dalam bentuk ester dapat meningkatkan aktivitas antidiabetes dari senyawa induk. Tujuan penelitian ini adalah untuk menentukan aktivitas antidiabetes dari senyawa naringenin dan senyawa ester dari naringenin. Penelitian ini dilakukan dengan penambatan secara in siliko dari molekul senyawa uji naringenin, serta turunan ester dari naringenin dengan penambatan secara in siliko terhadap Phosphoenolpyruvate Carboxykinase (PEPCK) yang diunduh via Protein Data Bank (PDB) dengan kode protein 1KHB. Selanjutnya dilakukan proses penambatan dengan program PLANTS, dan kemudian dilakukan evaluasi nilai energi ikatan hasil proses penambatan. Proses penambatan kembali molekul ligan asli ke dalam molekul kantung ikatan Phosphoenolpyruvate Carboxykinase (PEPCK) diperoleh nilai Root Mean Square Deviation (RMSD) 0,7670 Å. Penambatan molekul senyawa uji senyawa turunan ester dari naringenin menunjukkan aktivitas yang lebih baik dengan nilai energi ikatan yang lebih rendah bila dibandingkan dengan senyawa induk naringenin. Diabetes mellitus is a disease suffered by many around the world. There are many available synthetic medications for diabetes mellitus treatment. However, there are urgent needs to produce a better anti-diabetic especially from natural sources. Previous studiesindicated that flavonoid is asecondary metabolite from plants which has good anti-diabetic function. Naringenin is a flavonoid from orange which has anti-diabetic activity. The lipophilic derivative compound of naringenin flavonoid in ester form can increase the anti-diabetic activity from the parent compound. This research objectives were to determine the anti-diabetic activity of naringenin compounds and its ester compounds. This research was conducted using in silico docking ofcompound molecule of naringenin and also the ester derivation from naringenin with in silico docking to PhosphoenolpyruvateCarboxykinase (PEPCK) downloaded via Protein Data Bank (PDB) using 1 KHB protein code. Furthermore, docking process was conducted using PLANTS program, and also the bond energy value evaluation of the docking process. The ligand molecule docked in bag of bonds molecule (PhosphoenolpyruvateCarboxykinase (PEPCK) and the Root Mean Square Derivation (RMSD) with the value of 0.7670 Å was obtained. The naringenin ester derivation docking test indicated a better activity with a lower bond energy value than the naringenin parent compound.

scholarly journals POTENSI SENYAWA AKTIF BUNGA, KULIT DAUN DAN GETAH Aloe barbadensis Miller. TERHADAP PENGHAMBATAN ENZIM TYROSINASE

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Nur Aji
Keyword(s):  
Ferulic Acid ◽  
Protein Data Bank ◽  
In Silico ◽  
Sinapic Acid ◽  
Aloe Vera ◽  
Data Bank ◽  
Gentisic Acid ◽  
Aloe Barbadensis ◽  
Molegro Virtual Docker

Pada penelitian ini dilakukan simulasi penambatan molekul senyawa-senyawa aktif pada bunga, kulit daun dan getah tanaman Aloe barbadensis Miller . Simulasi ini bertujuan untuk memprediksi interaksi antara senyawa ligan uji dan protein yang menyebabkan terganggunya pembentukan melanin melalui interaksi kompetitif dengan enzim tirosinase. Simulasi penambatan molekul dilakukan menggunakan program Molegro Virtual Docker 6.0 dan prediksi permeabilitas dan sensitisasi kulit dengan pkCSM. Sebagai reseptor target digunakan struktur 3D protein 5M8P (tirosinase) dan ligan referensi TYR_516 (L-tirosin) yang diunduh dari Protein Data Bank. Posisi penambatan dilakukan pada koordinat yang sama dengan posisi ligan referensi yang sudah tertambat sebelumnya dan tervalidasi. Dari hasil simulasi diketahui bahwa dari 32 senyawa aktif dalam kulit daun, bunga dan getah aloe vera secara in silico terdapat tujuh senyawa yang potensial yang memiliki efek penghambatan tirosinase yaitu Aloesin, Cafeic Acid, Ferulic Acid, Galic Acid, Gentisic Acid, Protocathecuic Acid dan Sinapic Acid sedangkan berdasarkan energi interaksi potensi terbesar adalah Caffeic Acid.Kata kunci :Aloe barbadensis, Molegro, Enzim, Tirosinase, pkCSM.

Synthesis, antineoplastic activity and in silico studies of (S)-N-(1-hydroxy-3-methylbutan-2-yl)-3-(p-tolyl)-1,2,4-oxadiazole-5-carboxamide

2021 ◽  
Vol 25 (7) ◽  
pp. 167-176
Author(s):  
Cláudia Laís Araújo Almeida Santos ◽  
Jonh Anderson Macêdo Santos ◽  
Rodrigo Ribeiro Alves Caiana ◽  
Silvia Maria Souza ◽  
Jucleiton José Rufino Freitas ◽  
...  
Keyword(s):  
In Silico ◽  
Low Cost ◽  
Docking Study ◽  
New Drugs ◽  
Molecular Docking Study ◽  
Traditional Medicines ◽  
In Silico Studies ◽  
In Silico Study ◽  
Pharmacokinetic Properties ◽  
Low Toxicity

The development of chemotherapy agents without side effects is a major challenge, since traditional medicines usually have undesirable properties such as high toxicity, resistance and low bioavailability. In this sense, computational methods play a crucial role in the discovery and optimization of new drugs, as they combine speed and efficiency with low cost. The 1,2,4-oxadiazoles are one of the main classes of heterocyclics due to their numerous biological applications. In this work, we report the synthesis, antineoplastic evaluation and in silico study of a new 1,2,4-oxadiazole. The (S)-N-(1-hydroxy-3-methylbutan-2-yl)-3-(p-toluyl)-1,2,4-oxadiazole-5-carboxamide was obtained after two reaction steps in excellent yield. Although it has shown low activity in relation to the MCF-7, HCT116 and HL60 tumor cell lines, the molecular docking study indicates that this compound acts in the colchicine site and can inhibit tubulin polymerization. From the calculation of pharmacokinetic properties by the SwissADME and Osiris Property Explorer programs, it is possible to infer that the compound meets the Lipinski rules presenting good oral bioavailability and low toxicity.

IN SILICO ANALYSIS OF BRUGUIERA GYMNORRHIZA (L.) – LARGE LEAVED MANGROVE FOR EFFICIENT THERAPEUTIC USES

2021 ◽  
pp. 66-68
Author(s):  
ARUNPRASATH A ◽  
SREERAM S
Keyword(s):  
In Silico ◽  
In Silico Analysis ◽  
Data Bank ◽  
Plant Sample ◽  
Bruguiera Gymnorrhiza ◽  
Leaf Sample ◽  
Chemical Structures ◽  
Antimicrobial Studies ◽  
Therapeutic Uses ◽  
In Silico Studies

Objective: The study was focused on obtaining the therapeutic advantages of Bruguiera gymnorrhiza, a large leafed mangrove through in silico studies. Methods: The collected leaf sample was extracted using ethanol, and the extract was subjected to GCMS analysis to find out the compounds present in them. The obtained compounds underwent absorption, distribution, metabolism, and elimination toxicity test and the chemical structures were obtained from PUBCHEM and the disease which had more susceptibility was taken on the basis of antimicrobial studies and its protein structure was also obtained from Protein Data Bank. Maestro is a freely available, full future molecular visualization tool. It is a powerful tool for interpreting, managing, and sharing the results of computational experiments when coupled with Schrodinger software such as Glide, Prime, or Phase. The compatibility of ligand-protein interaction was visualized through the visualization software that is Pymol. Results: The retrieved compounds were subjected to analyze the absorption, distribution, metabolism, and excretion properties and the results were tabulated. It was found that the compound 2-Methoxy-4-Vinylphenol; 7786-61-0; 4-Vinylguaiaco from the plant sample B. gymnorrhiza shows a glide score (G. score) −7.2 Kcal/mol. The interactions were observed using Pymol. Conclusion: It was found that the compound 4-Vinylguaiaco from the plant sample B. gymnorrhiza can be used as potent drug for the treatment of pharyngitis, which is the inflammation of pharynx. This work can be taken as a base for the works that need to be done in future for the development of an effective drug and also addressing the importance of mangroves in the field of ethnobotany.

In Silico Investigation of the SARS CoV2 Protease with Thymoquinone Major Constituent of Nigella Sativa

2020 ◽  
Vol 17 ◽  
Author(s):  
Youness Kadil ◽  
Mohammed Mouhcine ◽  
Houda Filali
Keyword(s):  
Antiviral Activity ◽  
Beneficial Effect ◽  
In Silico ◽  
Nigella Sativa ◽  
Data Bank ◽  
Major Constituent ◽  
Potential Treatment ◽  
Ligand Interactions ◽  
New Type ◽  
Inhibitory Activities

: The COVID-19 caused by a new type of coronavirus has emerged from China and led to thousands of deaths globally. Despite many groups engaged in studying the newly emerged virus and searching for the treatment, the understanding of the SARS-CoV2 target ligand interactions represents a key challenge. Several studies are being conducted to identify potential treatment. Alternatively, the results of numerous studies have shown that protease inhibitors can be a genuine leader in research. The antiviral activity and beneficial effect against respiratory disorders of thymoquinone have been largely demonstrated. The aim of this study is to testing In Silico the inhibition of the replication of SARS CoV2 by thymoquinone. This is a molecular simulation study using SARS CoV2 protease and thymoquinone structures provided by Protein Data Bank. The preliminary results have shown that thymoquinone may have inhibitory activities against SARS CoV2 protease. Furthermore, given the demonstrated results of thymoquinone, we can conclude that it may be considered as an effective or adjuvant treatment for SARS CoV2 infection.

scholarly journals IN SILICO STUDY OF SIRT1 ACTIVATORS USING A MOLECULAR DYNAMIC APPROACH

2019 ◽  
pp. 237-245
Author(s):  
AZMINAH AZMINAH ◽  
MAKSUM RADJI ◽  
ABDUL MUN’IM ◽  
REZI RIADHI SYAHDI ◽  
ARRY YANUAR
Keyword(s):  
Molecular Dynamic ◽  
Bond Energy ◽  
In Silico ◽  
Interaction Analysis ◽  
Molecular Mechanic ◽  
Data Bank ◽  
Physicochemical Characteristics ◽  
Hydrogen Bond Interactions ◽  
In Silico Study ◽  
Sirt1 Activator

Objective: The importance of SIRT1 activator’s role in antidiabetic and anti-aging therapies is widely demonstrated. Drug discovery and developmentare time consuming. Drug design can be performed in silico using molecular dynamic approaches to accelerate and facilitate identification of the bestcompound candidates and their physicochemical characteristics and hit-to-lead selection.Methods: In silico study of SIRT1 activator for complexes using of Protein Data Bank (PDB) IDs 4ZZI, 4ZZJ 4ZZH, and 5BTR and 4TO ligand. Ligand–receptor interactions and bond energies were determined using molecular docking with the AutoDock4Zn program. Then, the complex with thebest bond energy was identified using a simulation of the molecular dynamics (50 ns) using the Amber program, and values for root mean squaredeviation, root mean square fluctuation, and bond energy were determined using the Molecular Mechanic–Poisson Boltzmann (Generalized Born)surface area (MM-PB[GB]SA) calculation.Results: Interaction analysis between activator ligand (4TO) and the SIRT1 receptor (PDB IDs 4ZZJ and 5BTR) revealed the ligand’s selectivity forhydrophobic interaction at Leu206, Ile223, Ile227, and hydrophilic interaction at Asn226, Glu230. Hydrogen bond interactions between Glu230 and Arg234(allosteric region) with Arg446, Val459, His473, and Asp475 (catalytic region) brought them close to the bounding substrate area. Bond energy valuesobtained using the MM-GB(PB)SA calculation showed 4TO interaction with 4ZZJ (MMGBSA ΔG, −31.4729–−26.6756; MMPBSA ΔG, −32.6292–−28.486].The bond energy value of the 4TO interaction with 5BTR showed MMGBSA ΔG = −40.6255–−30.0653 and MMPBSA ΔG = −34.6713–−25.9951.Conclusions: These findings provide important information on the target interaction of the bonds to the more selective SIRT1 activator useful fordrug discovery and development.

scholarly journals Proapoptosis Effect of Root of Eurycoma longifolia (Pasak Bumi) on the Prostate Cancer: In Silico Analysis

2020 ◽  
Vol 20 ◽  
pp. 03003
Author(s):  
Eka Yudha Rahman ◽  
Mulyohadi Ali ◽  
Basuki Bambang Purnomo ◽  
Nia Kania
Keyword(s):  
Prostate Cancer ◽  
In Silico ◽  
Caspase 3 ◽  
In Silico Analysis ◽  
Data Bank ◽  
Active Ingredients ◽  
Caspase 9 ◽  
Active Compounds ◽  
Eurycoma Longifolia ◽  
Silico Analysis

This study aimed to predict the proapoptosis effect of E. longifolia active compounds on prostate cancer by in silico analysis. Protein data such as BCL-2 (GI: 2506216), Caspase 3 (GI: 6978605), Caspase 8(GI: 11560103), data quassinoid (ID: 5459060 and chantin (ID: 97176) were collected from GenBank of NCBI. Protein BCL-2 collected from NCBI compare with Protein Data Bank (PDB) and UNIPROT. The docking process was carried out using software HEX 8.0. to compute the binding affinity between ligands (active compounds of Pasak Bumi) and protein target. The interaction between quassinoid and chantin was strongest and stable against caspase-9, indicating that the active ingredient in E. longifolia triggered caspase-9 activity after activation of BH3 domains in Bcl-2 in prostate cancer. The low energy binding between quassinoid and chantin with caspase-3 indicates the interaction between the active ingredients is not strong with caspase-3. E. longifolia active ingredients that are potentially used in the treatment of prostate cancer are quassinoid and chantin by inducing apoptotic mechanisms via both extrinsic and intrinsic pathways. The combination of active ingredients of E. longifolia that is quassinoid and chantin can be used as a strategy of prostate cancer therapy both through extrinsic and intrinsic pathways.

Sign in / Sign up

Export Citation Format

Share Document