scholarly journals Synthesis and Molecular Docking Studies of some Pyrano[2,3-c] Pyrazole as an Inhibitor of SARS-Coronavirus 3CL Protease

2021 ◽  
Vol 11 (3) ◽  
pp. 3780-3801
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Antiviral Treatment ◽  
Specific Treatment ◽  
Docking Studies ◽  
Strong Hydrogen Bond ◽  
Active Site Residues ◽  
Hydrogen Bond Interaction ◽  
Main Protease ◽  
3Cl Protease

The widespread global COVID-19 pandemic due to the lack of specific treatment and the urgent situation requires the use of all resources to remedy this scourge. The current study aimed to use molecular docking tools to find potential drug candidates for treatment. The pyrano[2,3-c] pyrazole 5(a-e) was targeted against the Main protease (Mpro), which plays a vital role in the replication and transcription of the Corona viral genome. The 3CL Protease (PDB ID 6LU7) was modeled, and the compounds were docked using Autodock Vina software, and ADMET data have been studied. All synthesized compounds were well engaged into the active site of the main protease with strong hydrogen bond interaction and a good score of energy. The 5b have been classed as the best inhibitor with an energy score of -6.2 kcal/mol, similar to the one given by chloroquine (-6.2Kcal/mol). Moreover, the molecular interaction studies showed that protease structure had multiple active site residues for all studied compounds. Our finding confirms the potential of these derivatives as lead compounds against the selected target protein of coronavirus, which needs further analysis and dynamic simulation studies to propose then develop a new antiviral treatment.

Synthesis, characterization and molecular docking studies on some new N-substituted 2-phenylpyrido[2,3-d]pyrimidine derivatives

2021 ◽  
pp. 3846-3854
Author(s):  
Vivek B. Panchabhai ◽  
Santosh R. Butle ◽  
Parag G. Ingole
Keyword(s):  
Crystal Structure ◽  
Antibacterial Activity ◽  
Molecular Docking ◽  
Active Site ◽  
Docking Studies ◽  
Biotin Carboxylase ◽  
Active Site Residues ◽  
Pyrimidine Derivatives ◽  
Molecular Docking Studies ◽  
Novel Scaffold

We report a novel scaffold of N-substituted 2-phenylpyrido(2,3-d)pyrimidine derivatives with potent antibacterial activity by targeting this biotin carboxylase enzyme. The series of eighteen N-substituted 2-phenylpyrido(2,3-d)pyrimidine derivatives were synthesized, characterized and further molecular docking studied to determine the mode of binding and energy changes with the crystal structure of biotin carboxylase (PDB ID: 2V58) was employed as the receptor with compounds 6a-r as ligands. The results obtained from the simulation were obtained in the form of dock score; these values represent the minimum energies. Compounds 6d, 6l, 6n, 6o, 6r and 6i showed formation of hydrogen bonds with the active site residues and van Der Walls interactions with the biotin carboxylase enzyme in their molecular docking studies. This compound can be studied further and developed into a potential antibacterial lead molecule.

scholarly journals Identification of Bioactive Phytoconstituents from the Plant Euphorbia hirta as Potential Inhibitor of SARS-CoV-2: an In-Silico Approach

2021 ◽  
Vol 12 (2) ◽  
pp. 1385-1396
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Biological Activities ◽  
Specific Treatment ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Standard Drug ◽  
Euphorbia Hirta ◽  
Main Protease

Currently, the entire globe is under the deadliest pandemic of Covid-19 caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). At present, no specific treatment is available to combat COVID-19 infection. Euphorbia hirta (Euphorbiaceae) have been reported for a variety of biological activities, including antiviral. The present investigation aimed to identify potential phytoconstituents of the plant E. hirta from the category flavonoids and coumarins against the SARS-CoV-2 using in silico approach. The molecular docking studies were performed using two different targets of SARS-CoV-2, namely Main protease (Mpro; PDB ID: 6M2N) and RNA-dependent RNA polymerase (RdRp; PDB ID: 7BW4). Based on the molecular docking study in comparison with standard drug, four compounds, namely Euphrobianin, Quercetin, 3-o-alpha-rhamnoside, Isoquercitrin, and rutin, were screened against the target Mpro. Three phytoconstituents, euphorbianin, myricetin, and rutin, were screened against the target RdRp. In the in silico toxicity studies of screened phytoconstituents, except myrectin all were predicted safe. Results of euphorbianin and rutin were found more interesting as both compounds had high binding affinity against both targets. Finally, we want to conclude that euphrobianin, quercetin 3-o-alpha-rhamnoside, isoquercitrin, and rutin could be further explored rapidly as they may have the potential to fight against COVID-19.

scholarly journals Molecular Docking and Molecular Dynamics Studies of SARS-CoV-2 Inhibitors: Crocin, Digitoxigenin, Beta-Eudesmol and Favipiravir: Comparative Study

2021 ◽  
Vol 12 (4) ◽  
pp. 5591-5600
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulation ◽  
Comparative Study ◽  
Active Site ◽  
Antiviral Treatment ◽  
Docking Study ◽  
The Other ◽  
Dynamics Simulation ◽  
Main Protease

In this study, Crocin, Digitoxigenin, Beta-Eudesmol, and Favipiravir were docked in the active site of SARS-CoV-2 main protease (PDB code: 6LU7). The docking study was followed by Molecular Dynamics simulation. The result indicates that Crocin and Digitoxigenin are the structures with the best affinity in the studied enzyme's binding site. Still, Molecular Dynamics simulation showed that Digitoxigenin is the molecule that fits better in the active site of the main protease. Therefore, this molecule could have a more potent antiviral treatment of COVID-19 than the other three studied compounds.

Enzyme Inhibition, Kinetic, and Molecular Docking Studies of α-glucosidase

2020 ◽  
Vol 16 (2) ◽  
pp. 155-161
Author(s):  
Ebrahim S. Moghadam ◽  
Mohammad A. Faramarzi ◽  
Somayeh Imanparast ◽  
Mohsen Amini
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Competitive Inhibition ◽  
Kinetic Studies ◽  
Developed Countries ◽  
Docking Studies ◽  
Antidiabetic Activity ◽  
Active Site Residues ◽  
Efficient Treatment ◽  
Enzyme Active Site

Background: Diabetes mellitus (DM) is an important global health problem especially in developed countries and insufficient lifestyle induces this phenomenon. Finding efficient treatment for DM is an interesting goal for researchers. Objective: Herein we tried to design and synthesize a series of quinazoline derivatives and investigate their bioactivity as possible α-Glucosidase inhibitor agents. Method: Compounds 1-14 were synthesized using a multicomponent reaction. 1HNMR, 13C NMR, MS, and IR spectroscopy were used for the characterization of synthesized compounds. α- Glucosidase inhibitory activity of compounds 1-14 was evaluated using p-nitrophenyl‐α‐Dglucopyranoside (pNPG) as a substrate of the α-glucosidase enzyme (EC3.2.1.20, Saccharomyces cerevisiae). The mechanism of inhibition of the α-glucosidase enzyme was investigated using kinetic studies. Molecular docking was also done using autodock software to find the possible mode of interaction of compound 8 and the enzyme active site. Results: Most of the tested compounds showed higher activity in inhibition of the enzyme in comparison to the standard, acarbose. Compound 8 exerted the best activity with the IC50 value of 291.5 μM. A kinetic study indicated a competitive inhibition of the α-glucosidase enzyme by compound 8. Finally, docking studies showed the interactions between compound 8 and enzyme active site residues. Conclusion: 2,4-Diarylquinazoline scaffold has good antidiabetic activity, so it is interesting to synthesize more 2,4-diarylquinazoline derivatives and evaluate their antidiabetic activities.

scholarly journals PREDIKSI SENYAWA EUCALYPTUS SEBAGAI INHIBITOR POTENSIAL COVID-19 MAIN PROTEASE (Mpro) SECARA MOLECULAR DOCKING

2021 ◽  
Vol 6 (2) ◽  
pp. 77
Author(s):  
Muhammad Fauzi ◽  
Fauzi Rahman ◽  
Yulistia Budianti Soemari ◽  
Richa Purnamasari
Keyword(s):  
Free Energy ◽  
Molecular Docking ◽  
Active Site ◽  
Docking Studies ◽  
Therapeutic Drug ◽  
Free Energies ◽  
Virus Family ◽  
Main Protease ◽  
The World ◽  
Suitable Target

The development of cases infected with the COVID-19 virus in Indonesia continues to increase. COVID-19 is a member of the corona virus family that has spread throughout the world. The COVID-19 Main protease is considered a suitable target for drug design against SARS infection because it plays a role in the processing of polyproteins required for the reproduction of the coronavirus. Eucalyptus are claimed to be able to ward off the COVID-19 virus. Therefore it is necessary to evaluate the content of eucalyptus compounds against Main proteases by docking studies. Based on the results of research conducted using the active site on the Main protease, it is known that eucalyptus (-)-globulol, epiglobulol, and ledol compounds have free energies of -7.23 kcal/mol, -7.91 kcal/mol, and -7.39 kcal/mol, respectively. Remdesivir as a therapeutic drug for COVID-19 has a free energy of -7.67 kcal/mol. These three compounds bind to the amino acid Glu166 as remdisivir with the best binding affinity on the active site of the Main protease. So these three compounds have the potential to inhibit the COVID-19 virus.

scholarly journals Molecular Docking Unveils Prospective Inhibitors for the SARS-COV-2 Main Protease

2021 ◽  
Vol 50 (5) ◽  
pp. 1473-1483
Author(s):  
Fawad Ahmad ◽  
Saima Ikram ◽  
Jamshaid Ahmad ◽  
Irshad ur Rehman ◽  
Saeed Ullah Khattak ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
3D Structure ◽  
Viral Proteins ◽  
Crystallographic Structure ◽  
X Ray ◽  
Main Protease ◽  
Recent Emergence ◽  
Novel Coronavirus ◽  
3Cl Protease

The recent emergence of a novel coronavirus strain (SARS-CoV-2) has stimulated global efforts to identify potential drugs that target proteins expressed by this novel coronavirus. Among these, the main protease of SARS-CoV-2 (3CL-protease (3CLPro), also known as (MPro) is one of the best choices for the scientists to target. 3CLPro is involved in the processing of polyproteins into mature non-structural viral proteins. An X-ray crystallographic structure (PDB ID 6LU7) of this protein was obtained from the PDB database. ChemDiv libraries of ~80,000 antiviral and ~13,000 coronavirus-targeting molecules were screened against the 3D structure of 3CLPro of SARS-CoV-2. We have identified a panel of molecules that showed an activity and potentially block the active site of the SARS-CoV-2 main protease. These molecules can be investigated further to develop effective virus-inhibiting molecules to treat this highly distressing disease, causing extreme unrest across the globe.

scholarly journals Eucalyptol (1,8 cineole) from Eucalyptus Essential Oil a Potential Inhibitor of COVID 19 Corona Virus Infection by Molecular Docking Studies

2020 ◽  
Author(s):  
Arun Dev Sharma ◽  
inderjeet kaur
Keyword(s):  
Molecular Docking ◽  
Essential Oil ◽  
Active Site ◽  
Hydrophobic Interactions ◽  
Rna Virus ◽  
Docking Studies ◽  
Active Site Residues ◽  
Virus Family ◽  
Molecular Docking Studies ◽  
Corona Virus

Background: COVID-19, a member of corona virus family is spreading its tentacles across the world due to lack of drugs at present. Associated with its infection are cough, fever and respiratory problems causes more than 15% mortality worldwide. It is caused by a positive, single stranded RNA virus from the enveloped coronaviruse family. However, the main viral proteinase (Mpro/3CLpro) has recently been regarded as a suitable target for drug design against SARS infection due to its vital role in polyproteins processing necessary for coronavirus reproduction.Objectives: The present in silico study was designed to evaluate the effect of Eucalyptol (1,8 cineole), a essential oil component from eucalyptus oil, on Mpro by docking study.Methods: In the present study, molecular docking studies were conducted by using 1-click dock and swiss dock tools. Protein interaction mode was calculated by Protein Interactions Calculator.Results: The calculated parameters such as RMSD, binding energy, and binding site similarity indicated effective binding of eucalyptol to COVID-19 proteinase. Active site prediction further validated the role of active site residues in ligand binding. PIC results indicated that, Mpro/eucalyptol complexes forms hydrophobic interactions, hydrogen bond interactions and strong ionic interactions.Conclusions: Therefore, eucalyptol may represent potential treatment potential to act as COVID-19 Mpro inhibitor. However, further research is necessary to investigate their potential medicinal use.

scholarly journals Discovery of novel potential KIT inhibitors for the treatment of gastrointestinal stromal tumor

2021 ◽  
Vol 16 (1) ◽  
pp. 303-310
Author(s):  
Lili Jiang ◽  
Zhongmin Zhang ◽  
Zhen Wang ◽  
Yong Liu
Keyword(s):  
Molecular Docking ◽  
Gastrointestinal Stromal Tumor ◽  
Pharmacophore Modeling ◽  
Stromal Tumor ◽  
Strong Hydrogen Bond ◽  
Ligand Complex ◽  
Hydrogen Bond Interaction ◽  
Mutant Proteins ◽  
Docking Simulations ◽  
Pharmacophore Models

Abstract Numerous inhibitors of tyrosine-protein kinase KIT, a receptor tyrosine kinase, have been explored as a viable therapy for the treatment of gastrointestinal stromal tumor (GIST). However, drug resistance due to acquired mutations in KIT makes these drugs almost useless. The present study was designed to screen the novel inhibitors against the activity of the KIT mutants through pharmacophore modeling and molecular docking. The best two pharmacophore models were established using the KIT mutants’ crystal complexes and were used to screen the new compounds with possible KIT inhibitory activity against both activation loop and ATP-binding mutants. As a result, two compounds were identified as potential candidates from the virtual screening, which satisfied the potential binding capabilities, molecular modeling characteristics, and predicted absorption, distribution, metabolism, excretion, toxicity (ADMET) properties. Further molecular docking simulations showed that two compounds made strong hydrogen bond interaction with different KIT mutant proteins. Our results indicated that pharmacophore models based on the receptor–ligand complex had excellent ability to screen KIT inhibitors, and two compounds may have the potential to develop further as the future KIT inhibitors for GIST treatment.

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