scholarly journals The Study of Potential Antiviral Compounds from Indonesian Medicinal Plants as Anti-COVID-19 with Molecular Docking Approach

2021 ◽  
Vol 1 (1) ◽  
pp. 32-39
Author(s):  
Baiq Ressa Puspita Rizma ◽  
Agus Dwi Ananto ◽  
Anggit Listyacahyani Sunarwidhi
Keyword(s):  
Molecular Docking ◽  
Medicinal Plants ◽  
Virus Disease ◽  
Molecular Study ◽  
Ant System ◽  
Docking Score ◽  
Docking Approach ◽  
Rapid Transmission ◽  
Potent Drug ◽  
Potential Inhibitors

Corona Virus Disease 2019 (COVID-19) is a new strain of coronavirus called SARS-CoV-2, which was identified in Wuhan, China, in December 2019. The rapid transmission of COVID-19 from human to human forced researchers to find a potent drug by setting aside the time-consuming traditional method in drug development. The molecular docking approach is one a reliable method to screening compound from chemical drug or by finding a compound from Indonesian herbal plants. The present study aimed to assess the potency of compounds from five medicinal plants as potential inhibitors of PLpro and 3CLpro from SARS-CoV-2 using molecular study. The molecular docking was performed using Protein-Ligand Ant System (PLANTS) to analyze the potential compounds by the docking score. Remdesivir triphosphate was used as a standard for the comparison of the test compounds. The docking score obtained from the docking of PLpro with native ligand, remdesivir triphosphate, curcumin, demethoxycurcumin, bisdemethoxycurcumin, luteolin, apigenin, quercetin, kaempferol, formononetin-7-O-glucuronide, andrographolide, and neoandrographolide were -111.441, -103.827, -103.609, -102.363, -100.27, -79.6655, -78.6901, -80.9337, -79.4686, -82.1124, -79.1789, and -97.2452, respectively. Meanwhile, docking score with 3CLpro for the same ligand were -64.0074, -86.1811, -81.428, -87.1625, -78.2899, -73.4345, -70.3368, -71.5539, -68.4321, -72.0154, -75.9777, and -93.7746. The docking score data suggest that curcumin was the most potential as a PLpro inhibitor, while neoandrographolide was the best as a 3CLpro inhibitor.

scholarly journals Molecular Study of Antiviral Compound of Indonesian Herbal Medicine as 3CLpro and PLpro Inhibitor in SARS-COV-2

2021 ◽  
Vol 4 (2) ◽  
pp. 127-134
Author(s):  
Baiq Ressa Puspita Rizma ◽  
Yek Zen Mubarok ◽  
Dian Fathita Dwi Lestari ◽  
Agus Dwi Ananto
Keyword(s):  
Molecular Docking ◽  
Molecular Study ◽  
Synergy Effect ◽  
Structural Protein ◽  
Antiviral Compound ◽  
Docking Score ◽  
Antiviral Compounds ◽  
Natural Ligands ◽  
Docking Approach ◽  
Rapid Transmission

Rapid transmission of COVID-19 disease and the fatal effects of the disease lead researchers to use various way to find potential anti-COVID-19 compounds, including using modern approaches. Molecular docking is one of the methods that can be used to analyse antiviral compounds and its molecular target from Indonesian herbs that are believed to have properties as anti-COVID-19. This study aims to analyse antiviral compounds from 5 herbs that have the potential as inhibitors of PLpro and 3CLpro, which both are a non-structural protein in SARS-CoV-2 by molecular docking approach using PLANTS. Remdesivir triphosphate, the active metabolite of remdesivir, was used as the comparison compound in studies. The results showed docking scores obtained from interactions between natural ligands, remdesivir trifospat, curcumin, demetoksikurkumin, bisdemetoksikurkumin, luteolin, apigenin, kuersetin, kaempferol, formononrtin-7-O-glucoronide, androgafolide, and neoandrogafolide with PLpro are as follows -111,441, -103,827, -103,609, -102,363, -100,27,-79,6655, -78.6901, -80.9337, -79.4686, -82.1124, -79.1789, and -97.2452.Combination between quercetin, neoandrographolide, bisdemethoxycurcumin, demetoxycurcumin, and curcumin showed a synergy effect by reduce its docking score. Meanwhile its interaction with the protein 3CLpro showed docking score for those compounds as follows 64.0074, -86.1811, -81.428, -87.1625, -78.2899, -73.4345,-70,3368, -71.5539, -68.4321, -72.0154, -75.9777 and -93.7746.Combination between andrographolide, neoandrographolide, bisdemethoxycurcumin, demetoxycurcumin and curcumin, also shows synegy effect in 3CLpro allow them to reduce the docking score.This study concludes that curcumin was known as the most potent compound that act as a PLpro inhibitor based on a docking score of -103,609, while in 3CLpro all the compound have a potential to inhibit 3CLpro with demethosxycurcumin and  neoandrogafolide as the most potent compound with a docking score -87,126 and -93.7746.

In silico drug design: development of new pyrimidine-based benzo-thiazole derivatives, selective for CDK2

2021 ◽  
Vol 18 ◽  
Author(s):  
Rania Kasmi ◽  
Larbi Elmchichi ◽  
Abdellah El Aissouq ◽  
Mohammed Bouachrine ◽  
Abdelkrim Ouammou
Keyword(s):  
Colon Cancer ◽  
Molecular Docking ◽  
In Silico ◽  
3D Qsar ◽  
Bioactive Molecules ◽  
Cancer Drugs ◽  
Qsar Studies ◽  
Benzothiazole Derivatives ◽  
Docking Approach ◽  
Potential Inhibitors

Backgroud: Kinases are proteins that control many biological functions. They are involved in cellular regulation, and many of them are deregulated in cancer proliferation. The evidence of this deregulation in many pathologies served as the origin of kinases as a therapeutic class and constitutes the motive that leads numerous teams to search for inhibitors of these targets. Objective: Based on 3D-QSAR studies and the molecular docking approach, we have developed new potential inhibitors that could be optimized and transformed into colon cancer drugs. Objective: Based on 3D-QSAR studies and the molecular docking approach, we have developed new potential inhibitors that could be optimized and transformed into colon cancer drugs. Method: To design new bioactive molecules and study their interactions with the cyclin-depend kinase type 2 (CDK2) enzyme, we used two virtual screening methods: 3D-QSAR modeling and molecular docking on a series of 28 pyrimidine-based benzothiazole derivatives. Results: To develop models (3D QSAR) we used CoMFA and CoMSIA techniques using SYBYL-X2.0 molecular modeling software. The statistical parameters reveal that the good CoMFA model displays (Q²= 0.587; R²= 0.895) and that of CoMSIA displays (Q²= 0.552; R²= 0.768) which are considered to be very good internal prediction values, while an external validation of a test series of 5 compounds not included in the model development series gives R²test values of 0.56 for CoMFA and R²test values of 0.51 for CoMSIA. The molecular docking approach with AutoDockTools-1.5.6 is introduced in this work to enrich the interpretations extracted from the CoMFA and CoMSIA contour maps, and to provide an in silico research method for the most favorable mode of interaction of an inhibitor within its receptor (CDK2). Conclusion: We have constructed and validated a quantitative 3D model of structure-activity relation-ships of pyrimidine-based benzothiazole derivatives as CDK2 inhibitors. This model allows us to identify the nature and position of the groups that enhance the activity, giving us directions to discover new, more powerful molecules in a limited time.

scholarly journals Investigation of the anti-TB potential of selected alkaloid constituents using molecular docking approach

2020 ◽  
Author(s):  
Mohammad Kawsar Sharif Siam ◽  
Mohammad Umer Sharif Shohan ◽  
Zaira Zafroon
Keyword(s):  
Free Energy ◽  
Mycobacterium Tuberculosis ◽  
Molecular Docking ◽  
Protein Binding ◽  
Binding Free Energy ◽  
Chemical Constituents ◽  
Biological Evaluation ◽  
Natural Sources ◽  
Docking Score ◽  
Docking Approach

AbstractMycobacterium tuberculosis, the leading bacterial killer disease worldwide, causes Human tuberculosis (TB). Due to the growing problem of drug resistant Mycobacterium tuberculosis strains, new anti-TB drugs are urgently needed. Natural sources such as plant extracts have long played an important role in tuberculosis management and can be used as a template to design new drugs. A wide screening of natural sources is time consuming but the process can be significantly sped up using molecular docking. In this study, we used a molecular docking approach to investigate the interactions between selected natural constituents and three proteins MtPanK, MtDprE1 and MtKasA involved in the physiological functions of Mycobacterium tuberculosis which are necessary for the bacteria to survive and cause disease. The molecular docking score, a score that accounts for the binding affinity between a ligand and a target protein, for each protein was calculated against 150 chemical constituents of different classes to estimate the binding free energy. The docking scores represent the binding free energy. The best docking scores indicates the highest ligand protein binding which is indicated by the lowest energy value. Among the natural constituents, Shermilamine B showed a docking score of - 8.5kcal/mol, Brachystamide B showed a docking score of −8.6 kcal/mol with MtPanK, Monoamphilectine A showed a score of −9.8kcal/mol with MtDprE1.These three compounds showed docking scores which were superior to the control inhibitors and represent the opportunity of in vitro biological evaluation and anti-TB drug design. Consequently, all these compounds belonged to the alkaloid class. Specific interactions were studied to further understand the nature of intermolecular bonds between the most active ligands and the protein binding site residues which proved that among the constituents monoamphilectine A and Shermilamine B show more promise as Anti-TB drugs. Furthermore, the ADMET properties of these compounds or ligands showed that they have no corrosive or carcinogenic parameters.Graphical Abstract

scholarly journals Computational Molecular Docking and Virtual Screening Revealed Promising SARS-CoV-2 Drugs

2020 ◽  
Author(s):  
Maryam Hosseini ◽  
Wanqiu Chen ◽  
Charles Wang
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Virtual Screening ◽  
Clinical Studies ◽  
Inhibitory Effect ◽  
Docking Approach ◽  
Novel Coronavirus ◽  
Approved Drugs ◽  
Potential Inhibitors ◽  
Computational Molecular Docking

The pandemic of novel coronavirus disease 2019 (COVID-19) is rampaging the world with more than 1.4 million of confirmed cases and more than 85,000 of deaths across world by April 9th, 2020. There is an urgent need to identify effective drugs to fight against the virus. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the family of coronaviruses consisting of four structural and 16 non-structured proteins. Three non-structural proteins such as main protease, papain like protease, and RNA-dependent RNA polymerase are believed to play a crucial role in the virus replication. We applied a computational ligand-receptor binding modeling and performed a comprehensive virtual screening on the FDA-approved drugs against these three SARS-CoV-2 proteins using AutoDock Vina. Our computational studies indicated that Simeprevir, Ledipasvir, Idarubicin, Saquinavir, Ledipasivir, Partitaprevir, Glecaprevir, and Velpatasvir are all promising inhibitors, which displayed a lower binding energy (higher inhibitory effect) than Remdesivir, Lopinavir, and Ritonavir. However, we found that chloroquine and hydroxychloroquine, which showed efficacy in treating the COVID-19 in recent clinical studies, had high binding energy with all three proteins, suggesting they may work through a different mechanism. We also identified several novel drugs as potential inhibitors against SARS-CoV-2, including antiviral Raltegravir; antidiabetic Amaryl; antibiotics Retapamulin, Rifimixin, and Rifabutin; antiemetic Fosaprepitant and Netupitant. In summary, our computational molecular docking approach and virtual screening identified some promising candidate SARS-CoV-2 drugs that may be considered for further clinical studies.

scholarly journals Molecular docking analysis of COX-2 for potential inhibitors

2020 ◽  
Vol 16 (10) ◽  
pp. 753-758
Author(s):  
Jayaraman Selvaraj ◽  
Keyword(s):  
Breast Cancer ◽  
Molecular Docking ◽  
Medicinal Plants ◽  
Cyclooxygenase 2 ◽  
Docking Analysis ◽  
Natural Alkaloid ◽  
Cox 2 ◽  
Potential Inhibitors ◽  
Molecular Docking Analysis

Cyclooxygenase-2 (COX-2) is liked with breast cancer. Therefore, it is of interest to design and develop new yet effective compounds against COX-2 from medicinal plants such as the natural alkaloid compounds. We document the optimal binding features of aristolochicacid with COX-2 protein for further consideration.

Improved procedure of the search for poly(ADP-Ribose) polymerase-1 potential inhibitors with the use of the molecular docking approach

2011 ◽  
Vol 45 (3) ◽  
pp. 517-521 ◽  
Author(s):  
A. L. Zakharenko ◽  
M. V. Sukhanova ◽  
S. N. Khodyreva ◽  
F. N. Novikov ◽  
V. S. Stroylov ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Approach ◽  
Potential Inhibitors

scholarly journals MOLECULAR DOCKING STUDY BETWEEN 3 THAI MEDICINAL PLANTS COMPOUNDS AND COVID-19 THERAPEUTIC PROTEIN TARGETS: SARS-COV-2 MAIN PROTEASE, ACE-2, AND PAK-1

2021 ◽  
pp. 41-48
Author(s):  
SAFIRA CANDRA ASIH ◽  
RAFIDHA IRDIANI ◽  
MUHAMAD SAHLAN ◽  
MOHAMMAD NASIKIN
Keyword(s):  
Molecular Docking ◽  
Medicinal Plants ◽  
Profile Analysis ◽  
Binding Free Energy ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Protein Targets ◽  
Main Protease ◽  
Docking Approach ◽  
Thai Medicinal Plants

Objective: The present study aimed to evaluate those 3 compounds among 122 Thai natural products by using a molecular docking approach to inhibit Main Protease (Mpro) of SARS-CoV-2 (PDB code: 6Y2F), Angiotensin Converting Enzyme (ACE)-2 (PDB code: 1R4L), and PAK-1 kinase (PDB code: 5DEW). Methods: The evaluation was performed on the docking scores calculated using AutoDock Vina as a docking engine and interaction profile analysis through 2-dimensional visualization using LigPlot+. The determination of the docking score was done by selecting the conformation of the ligand that has the lowest binding free energy (best pose). Result: The results of this study indicate that overall, Panduratin A has the best affinity in inhibiting the main protease of SARS-CoV-2, ACE-2, and PAK-1 compared to other compounds. Conclusion: The three thai medicinal plants compound has the potential to be developed as specific therapeutic agents against COVID-19.

scholarly journals Computational analysis by molecular docking of thirty alkaloid compounds from medicinal plants as potent inhibitors of SARS-CoV-2 main protease

2021 ◽  
Vol 4 (4) ◽  
pp. 487-503
Author(s):  
Tunga Kuhana A ◽  
◽  
Jason T. Kilembe ◽  
Aristote Matondo ◽  
Khamis M. Yussuf ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Medicinal Plants ◽  
Computational Analysis ◽  
Potential Drug ◽  
Lipinski’S Rule ◽  
Main Protease ◽  
Lipinski’S Rule Of Five ◽  
Potential Inhibitors ◽  
Therapeutic Profile

Year 2020 has been highly affected by the COVID-19 outbreak. The urgent need for a potent and effective drug for the treatment of this malignancy put pressure on researchers and scientists worldwide to develop a potential drug or a vaccine to resist SARS-CoV-2 virus. We report in this paper the assessment of the efficiency of thirty alkaloid compounds derived from African medicinal plants against the SARS-CoV-2 main protease through molecular docking and bioinformatics approaches. The results revealed four potential inhibitors (ligands 18, 21, 23 and 24) with 12.26 kcal/mol being the highest binding energy. Additionally, in silico drug-likeness and ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) properties for the four ligands showed a good predicted therapeutic profile of druggability, and fully obey the Lipinski's rule of five as well.

scholarly journals Investigation of the Anti-TB Potential of Selected Phytochemicals of Nigella Sativa using Molecular Docking Approach

2021 ◽  
pp. 278-286
Author(s):  
Shabir Ahmad Mir
Keyword(s):  
Molecular Docking ◽  
Drug Targets ◽  
Nigella Sativa ◽  
New Drugs ◽  
Docking Score ◽  
Discovery Studio ◽  
Biological Studies ◽  
Docking Approach ◽  
Novel Drug

Background: Tuberculosis (TB) is one of the foremost causes of human mortality across the world. In general, it is a curable disease and several drugs are available in market for its treatment, however, because of the drug resistance to the currently available anti-TB drugs, the development and/or discovery of new drugs with better efficacy against TB cannot be overlooked. In the present study, we performed virtual screening of the major phytochemicals of the plant Nigella sativa for investigating their potential to inhibit some novel drug targets of Mycobacterium tuberculosis, which included- pantothenate kinase, type 1 (MtPanK), β-ketoacyl ACP synthase I (MtKasA), and decaprenylphosphoryl-β-D-ribose 2′-epimerase 1 (MtDprE1). Methods: The screening of the phytochemicals was investigated through a molecular docking approach using Auto dock vina and the molecular interactions in the protein-ligand complexes were visualized and analysed through PyMol and BioVia Discovery Studio Visualizer. Results: Our in silico observations reveal that, out of the nine selected phytochemicals screened, five compounds, namely α-hederin, dithymoquinone, nigellidine, thymoquinone and thymol binded to one or more of the selected target enzymes with significant docking scores. α-hederin binded to MtDprE1 and MtKasA with a docking score of −8.5kcal/mol and −7.9kcal/mol, respectively, dithymoquinone binded to MtKasA, MtDprE1 and MtPanK with a docking score of −6.5kcal/mol, −8.2kcal/mol and −9.2kcal/mol, respectively and nigellidine binded to MtDprE1 and MtPanK with a docking score of −8.1kcal/mol and −8.2kcal/mol, respectively. Further, thymol as well as thymoquinone were observed to bind MtKasA with a docking score of −6.6kcal/mol. Conclusions: The results of our study indicate that the five phytochemicals of N. sativa, including α-hederin, dithymoquinone, nigellidine, thymoquinone and thymol, are worth studying further for their anti-TB activity, however, additional biological studies are warranted to validate these findings.

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