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 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 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.

Novel Thiazole-Based Thiazolidinones as Potent Anti-infective Agents: In silico PASS and Toxicity Prediction, Synthesis, Biological Evaluation and Molecular Modelling

2020 ◽  
Vol 23 (2) ◽  
pp. 126-140 ◽  
Author(s):  
Christophe Tratrat
Keyword(s):  
In Silico ◽  
Antimicrobial Agents ◽  
Target Identification ◽  
Biological Evaluation ◽  
Microbial Infection ◽  
Toxicity Prediction ◽  
Discovery Studio ◽  
Bacteria And Fungi ◽  
Multiple Drugs ◽  
Antibacterial And Antifungal

Aims and Objective: The infectious disease treatment remains a challenging concern owing to the increasing number of pathogenic microorganisms associated with resistance to multiple drugs. A promising approach for combating microbial infection is to combine two or more known bioactive heterocyclic pharmacophores in one molecular platform. Herein, the synthesis and biological evaluation of novel thiazole-thiazolidinone hybrids as potential antimicrobial agents were dissimilated. Materials and Methods: The preparation of the substituted 5-benzylidene-2-thiazolyimino-4- thiazolidinones was achieved in three steps from 2-amino-5-methylthiazoline. All the compounds have been screened in PASS antibacterial activity prediction and in a panel of bacteria and fungi strains. Minimum inhibitory concentration and minimum bacterial concentration were both determined by microdilution assays. Molecular modeling was conducted using Accelrys Discovery Studio 4.0 client. ToxPredict (OPEN TOX) and ProTox were used to estimate the toxicity of the title compounds. Results: PASS prediction revealed the potentiality antibacterial property of the designed thiazolethiazolidinone hybrids. All tested compounds were found to kill and to inhibit the growth of a vast variety of bacteria and fungi, and were more potent than the commercial drugs, streptomycin, ampicillin, bifomazole and ketoconazole. Further, in silico study was carried out for prospective molecular target identification and revealed favorable interaction with the target enzymes E. coli MurB and CYP51B of Aspergillus fumigatus. Toxicity prediction revealed that none of the active compounds was found toxic. Conclusion: Substituted 5-benzylidene-2-thiazolyimino-4-thiazolidinones, endowing remarkable antibacterial and antifungal properties, were identified as a novel class of antimicrobial agents and may find a potential therapeutic use to eradicate infectious diseases.

scholarly journals Identification of Potential HCV Inhibitors Based on the Interaction of Epigallocatechin-3-Gallate with Viral Envelope Proteins

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1257
Author(s):  
Fareena Shahid ◽  
Noreen ◽  
Roshan Ali ◽  
Syed Lal Badshah ◽  
Syed Babar Jamal ◽  
...  
Keyword(s):  
Hepatitis C ◽  
In Silico ◽  
Experimental Validation ◽  
Homology Modelling ◽  
Viral Envelope ◽  
Screening Methods ◽  
Binding Affinities ◽  
Autodock Vina ◽  
Potential Inhibitors ◽  
Very High

Hepatitis C is affecting millions of people around the globe annually, which leads to death in very high numbers. After many years of research, hepatitis C virus (HCV) remains a serious threat to the human population and needs proper management. The in silico approach in the drug discovery process is an efficient method in identifying inhibitors for various diseases. In our study, the interaction between Epigallocatechin-3-gallate, a component of green tea, and envelope glycoprotein E2 of HCV is evaluated. Epigallocatechin-3-gallate is the most promising polyphenol approved through cell culture analysis that can inhibit the entry of HCV. Therefore, various in silico techniques have been employed to find out other potential inhibitors that can behave as EGCG. Thus, the homology modelling of E2 protein was performed. The potential lead molecules were predicted using ligand-based as well as structure-based virtual screening methods. The compounds obtained were then screened through PyRx. The drugs obtained were ranked based on their binding affinities. Furthermore, the docking of the topmost drugs was performed by AutoDock Vina, while its 2D interactions were plotted in LigPlot+. The lead compound mms02387687 (2-[[5-[(4-ethylphenoxy) methyl]-4-prop-2-enyl-1,2,4-triazol-3-yl] sulfanyl]-N-[3(trifluoromethyl) phenyl] acetamide) was ranked on top, and we believe it can serve as a drug against HCV in the future, owing to experimental validation.

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 Studi Interaksi Molekuler Aktivitas Antimikroba Peptida Bioaktif terhadap Staphylococcus aureus Secara In silico

2020 ◽  
Vol 7 (2) ◽  
pp. 93
Author(s):  
Taufik Muhammad Fakih ◽  
Mentari Luthfika Dewi
Keyword(s):  
Staphylococcus Aureus ◽  
In Silico ◽  
Binding Protein ◽  
Pelteobagrus Fulvidraco ◽  
Penicillin Binding Protein ◽  
Discovery Studio

Pendahuluan: Lendir kulit ikan lele kuning (Pelteobagrus fulvidraco), mengandung peptida bioaktif dan banyak dimanfaatkan dalam pengobatan berbagai penyakit karena memiliki aktivitas biologis, diantaranya sebagai antimikroba. Beberapa peptida bioaktif tersebut, antara lain pelteobagrin, myxinidin, pleurocidin, dan pardaxin-P1 dan telah terbukti mampu menghambat Penicillin-Binding Protein 3 (PBP3) dari Staphylococcus aureus. Tujuan: Penelitian ini bertujuan untuk mengidentifikasi aktivitas antimikroba molekul peptida bioaktif secara in silico terhadap makromolekul Penicillin-Binding Protein 3 (PBP3) dari Staphylococcus aureus dan interaksi peptida bioaktif tersebut yang terlibat dalam mekanisme aksi antimikroba. Metode: Sekuensing peptida bioaktif terlebih dahulu dilakukan pemodelan ke dalam bentuk konformasi 3D menggunakan software PEP-FOLD. Konformasi terbaik hasil pemodelan dipilih untuk kemudian dilakukan studi penambatan molekuler terhadap makromolekul dari Staphylococcus aureus menggunakan software PatchDock. Interaksi molekuler yang terbentuk selanjutnya diidentifikasi lebih lanjut menggunakan software BIOVIA Discovery Studio 2020. Hasil: Berdasarkan hasil penambatan molekuler menunjukkan bahwa peptida bioaktif myxinidin memiliki afinitas paling baik dengan ACE score −2497,26 kJ/mol. Kesimpulan: Peptida bioaktif lendir kulit ikan lele kuning (Pelteobagrus fulvidraco) dapat dipertimbangkan sebagai kandidat antimikroba alami.

scholarly journals In Silico Screening for Natural Ligands to Non-Structural Nsp7 Conformers of Coronaviruses

2020 ◽  
Author(s):  
Rafael Blasco ◽  
Julio Coll
Keyword(s):  
In Silico ◽  
Chemical Properties ◽  
Structural Similarity ◽  
Binding Pocket ◽  
Binding Affinities ◽  
Structural Protein ◽  
Autodock Vina ◽  
Natural Ligands ◽  
Final Optimization

<p>The non-structural protein 7 (nsp7) of Severe Acute Respiratory Syndrome (SARS) coronaviruses was selected as a new target to potentially interfere with viral replication. The nsp7s are one of the most conserved, unique and small coronavirus proteins having a critical, yet intriguing participation on the replication of the long viral RNA genome after complexing with nsp8 and nsp12. Despite the difficulties of having no previous binding pocket, two high-throughput virtual blind screening of 158240 natural compounds > 400 Da by AutoDock Vina against nsp7.1ysy identified 655 leads displaying predicted binding affinities between 10 to 1100 nM. The leads were then screened against 14 available conformations of nsp7 by both AutoDock Vina and seeSAR programs employing different binding score algorithms, to identify 20 consensus top-leads. Further <i>in silico</i> predictive analysis of physiological and toxicity ADMET criteria (chemical properties, adsorption, metabolism, toxicity) narrowed top-leads to a few drug-like ligands many of them showing steroid-like structures. A final optimization by search for structural similarity to the top drug-like ligand that were also commercially available, yielded a collection of predicted novel ligands with ~100-fold higher-affinity whose antiviral activity may be experimentally validated. Additionally, these novel nsp7-interacting ligands and/or their further optimized derivatives, may offer new tools to investigate the intriguing role of nsp7 on replication of coronaviruses.</p>

scholarly journals Kaempferol-Mediated Sensitization Enhances Chemotherapeutic Efficacy of Sorafenib Against Hepatocellular Carcinoma: An In Silico and In Vitro Approach

2020 ◽  
Vol 10 (3) ◽  
pp. 472-476
Author(s):  
Bhagyalakshmi Nair ◽  
Ruby John Anto ◽  
Sabitha M ◽  
Lekshmi R. Nath
Keyword(s):  
Hepatocellular Carcinoma ◽  
Multidrug Resistance ◽  
Liver Cancer ◽  
In Silico ◽  
Culture Media ◽  
Positive Control ◽  
Advanced Hepatocellular Carcinoma ◽  
Discovery Studio ◽  
Toxic Concentrations

Purpose : Sorafenib is the sole FDA approved drug conventionally used for the treatment of advanced hepatocellular carcinoma (HCC). Despite of the beneficial use of sorafenib in the treatment of HCC, multidrug resistance still remains a challenge. HCC is inherently known as chemotherapy resistant tumor due to P-glycoprotein (P-gp)-mediated multidrug resistance. Methods: We studied the interaction energy of kaempferol with human multidrug resistance protein-1 (RCSB PDB ID: 2CBZ) using in silico method with the help of BIOVIA Discovery Studio. HepG2 and N1S1 liver cancer cell lines were treated in suitable cell culture media to evaluate the efficacy of kaempferol in chemo-sensitizing liver cancer cells towards the effect of sorafenib. Cell viability study was performed by MTT assay. Results: In silico analysis of kaempferol showed best docking score of 23.14 with Human Multi Drug Resistant Protein-1 (RCSB PDB ID: 2CBZ) compared with positive control verapamil. In in-vitro condition, combination of sub-toxic concentrations of both kaempferol and sorafenib produced 50% cytotoxicity with concentration of 2.5 µM each which indicates that kaempferol has the ability to reverse the MDR by decreasing the over-expression of P-gp. Conclusion: Kaempferol is able to sensitize the HepG2 and N1S1 against the sub-toxic concentration of sorafenib. Hence, we consider that the efficacy of sorafenib chemotherapy can be enhanced by the significant approach of combining the sub-toxic concentrations of sorafenib with kaempferol. Thus, kaempferol can be used as a better candidate molecule along with sorafenib for enhancing its efficacy, if validated through preclinical studies.

scholarly journals PEMODELAN MOLEKUL SENYAWA TURUNAN KOJIC ACID SERTA INTERAKSINYA DENGAN ENZIM TIROSINASE

2020 ◽  
Vol 24 (2) ◽  
pp. 54-58
Author(s):  
Fazrul Permadi
Keyword(s):  
Kojic Acid ◽  
Autodock Vina ◽  
Discovery Studio

Studi HKSA dilakukan pada turunan kojyl thioether sebagai inhibitor tirosinase. Perhitungan prediktotr dilakukan menggunakan aplikasi hyperchem 8.0 dengan metode optimasi geometri semi-empirik PM3. Analisis regresi multilinier menggunakan SPSS 25.0 untuk mencari hubungan antara prediktor dan aktivitas senyawa turunan kojyl thioether sebagai inhibitor tirosinase. Model persamaan HKSA terbaik adalah  :pIC50 = -922.517 + 15.872*ELUMO – 436.654*qC4 – 209.509*qC5 + 1.0008*Eintn = 14; m = 4; r = 0.949; R2 = 0.901; PRESS = 3.0469; q2 = 0.8246Berdasarkan persamaan HKSA diatas didapatkan 4 senyawa baru turunun kojyl thioether yang bisa dijadikan sebagai analog inhibitor tirosinase yang baru. Parameter pemilihan senyawa tersebut karena memiliki aktivitas yang lebih baik sebagai inhibitor tirosinase dibandingkan senyawa penuntun, tidak hepatotoksik, tidak menimbulkan AMES Toxicity, tidak menimbulkan skin sensititasion dan LD50 pada tikus masuk kategori relative tidak membahayakan. Untuk melihat interaksi antara senyawa turunun kojyl thioether dengan enzim tirosinase dilakukan docking menggunakan Autodock vina yang visualisasinya menggunakan discovery studio 2020 client. Hasil docking menunjukkan bahwa semua senyawa setidaknya memiliki satu interaksi pada residu asam amino yang sama dengan native ligan. yaitu Val283.

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