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.

scholarly journals Phytochemicals from Leucas zeylanica Targeting Main Protease of SARS-CoV-2: Chemical Profiles, Molecular Docking, and Molecular Dynamics Simulations

Biology ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 789
Author(s):  
Mycal Dutta ◽  
Abu Montakim Tareq ◽  
Ahmed Rakib ◽  
Shafi Mahmud ◽  
Saad Ahmed Sami ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulation ◽  
Surface Area ◽  
Dynamics Simulation ◽  
Solvent Accessible Surface Area ◽  
Gas Chromatography Mass Spectrometry ◽  
Radius Of Gyration ◽  
Hydrogen Bond Formation ◽  
Main Protease

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a contemporary coronavirus, has impacted global economic activity and has a high transmission rate. As a result of the virus’s severe medical effects, developing effective vaccinations is vital. Plant-derived metabolites have been discovered as potential SARS-CoV-2 inhibitors. The SARS-CoV-2 main protease (Mpro) is a target for therapeutic research because of its highly conserved protein sequence. Gas chromatography–mass spectrometry (GC-MS) and molecular docking were used to screen 34 compounds identified from Leucas zeylanica for potential inhibitory activity against the SARS-CoV-2 Mpro. In addition, prime molecular mechanics–generalized Born surface area (MM-GBSA) was used to screen the compound dataset using a molecular dynamics simulation. From molecular docking analysis, 26 compounds were capable of interaction with the SARS-CoV-2 Mpro, while three compounds, namely 11-oxa-dispiro[4.0.4.1]undecan-1-ol (−5.755 kcal/mol), azetidin-2-one 3,3-dimethyl-4-(1-aminoethyl) (−5.39 kcal/mol), and lorazepam, 2TMS derivative (−5.246 kcal/mol), exhibited the highest docking scores. These three ligands were assessed by MM-GBSA, which revealed that they bind with the necessary Mpro amino acids in the catalytic groove to cause protein inhibition, including Ser144, Cys145, and His41. The molecular dynamics simulation confirmed the complex rigidity and stability of the docked ligand–Mpro complexes based on the analysis of mean radical variations, root-mean-square fluctuations, solvent-accessible surface area, radius of gyration, and hydrogen bond formation. The study of the postmolecular dynamics confirmation also confirmed that lorazepam, 11-oxa-dispiro[4.0.4.1]undecan-1-ol, and azetidin-2-one-3, 3-dimethyl-4-(1-aminoethyl) interact with similar Mpro binding pockets. The results of our computerized drug design approach may assist in the fight against SARS-CoV-2.

scholarly journals Drug Binding Dynamics of the Dimeric SARS-CoV-2 Main Protease, Determined by Molecular Dynamics Simulation

2020 ◽  
Author(s):  
Teruhisa S. KOMATSU ◽  
Noriaki Okimoto ◽  
Yohei M. KOYAMA ◽  
Yoshinori HIRANO ◽  
Gentaro MORIMOTO ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Active Site ◽  
Binding Sites ◽  
Complex Structure ◽  
Drug Binding ◽  
Dynamics Simulation ◽  
Trajectory Data ◽  
Main Protease ◽  
Dynamic Sampling

<div> <div> <div> <p>We performed molecular dynamics simulation of the dimeric SARS-CoV-2 (severe acute respiratory syndrome corona virus 2) main protease (Mpro) to examine the binding dynamics of small molecular ligands. Seven HIV inhibitors, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, and tipranavir, were used as the potential lead drugs to investigate access to the drug binding sites in Mpro. The frequently accessed sites on Mpro were classified based on contacts between the ligands and the protein, and the differences in site distributions of the encounter complex were observed among the ligands. All seven ligands showed binding to the active site at least twice in 28 simulations of 200 ns each. We further investigated the variations in the complex structure of the active site with the ligands, using microsecond order simulations. Results revealed a wide variation in the shapes of the binding sites and binding poses of the ligands. Additionally, the C-terminal region of the other chain often interacted with the ligands and the active site. Collectively, these findings indicate the importance of dynamic sampling of protein- ligand complexes and suggest the possibilities of further drug optimisations. <br></p><p><br></p><p><br> </p><div> <div> <div> <p>Raw trajectory data analysed in this paper and movie examples are available at the zenodo repository.<br></p> </div> </div> </div> </div> </div> </div>

scholarly journals Drug binding dynamics of the dimeric SARS-CoV-2 main protease, determined by molecular dynamics simulation

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Teruhisa S. Komatsu ◽  
Noriaki Okimoto ◽  
Yohei M. Koyama ◽  
Yoshinori Hirano ◽  
Gentaro Morimoto ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Active Site ◽  
Binding Sites ◽  
Complex Structure ◽  
Drug Binding ◽  
Dynamics Simulation ◽  
Main Protease ◽  
Encounter Complex ◽  
Dynamic Sampling

Abstract We performed molecular dynamics simulation of the dimeric SARS-CoV-2 (severe acute respiratory syndrome corona virus 2) main protease (Mpro) to examine the binding dynamics of small molecular ligands. Seven HIV inhibitors, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, and tipranavir, were used as the potential lead drugs to investigate access to the drug binding sites in Mpro. The frequently accessed sites on Mpro were classified based on contacts between the ligands and the protein, and the differences in site distributions of the encounter complex were observed among the ligands. All seven ligands showed binding to the active site at least twice in 28 simulations of 200 ns each. We further investigated the variations in the complex structure of the active site with the ligands, using microsecond order simulations. Results revealed a wide variation in the shapes of the binding sites and binding poses of the ligands. Additionally, the C-terminal region of the other chain often interacted with the ligands and the active site. Collectively, these findings indicate the importance of dynamic sampling of protein–ligand complexes and suggest the possibilities of further drug optimisations.

scholarly journals Drug Binding Dynamics of the Dimeric SARS-CoV-2 Main Protease, Determined by Molecular Dynamics Simulation

2020 ◽  
Author(s):  
Teruhisa S. KOMATSU ◽  
Noriaki Okimoto ◽  
Yohei M. KOYAMA ◽  
Yoshinori HIRANO ◽  
Gentaro MORIMOTO ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Active Site ◽  
Binding Sites ◽  
Complex Structure ◽  
Drug Binding ◽  
Dynamics Simulation ◽  
Trajectory Data ◽  
Main Protease ◽  
Dynamic Sampling

<div> <div> <div> <p>We performed molecular dynamics simulation of the dimeric SARS-CoV-2 (severe acute respiratory syndrome corona virus 2) main protease (Mpro) to examine the binding dynamics of small molecular ligands. Seven HIV inhibitors, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, and tipranavir, were used as the potential lead drugs to investigate access to the drug binding sites in Mpro. The frequently accessed sites on Mpro were classified based on contacts between the ligands and the protein, and the differences in site distributions of the encounter complex were observed among the ligands. All seven ligands showed binding to the active site at least twice in 28 simulations of 200 ns each. We further investigated the variations in the complex structure of the active site with the ligands, using microsecond order simulations. Results revealed a wide variation in the shapes of the binding sites and binding poses of the ligands. Additionally, the C-terminal region of the other chain often interacted with the ligands and the active site. Collectively, these findings indicate the importance of dynamic sampling of protein- ligand complexes and suggest the possibilities of further drug optimisations. <br></p><p><br></p><p><br> </p><div> <div> <div> <p>Raw trajectory data analysed in this paper and movie examples are available at the zenodo repository.<br></p> </div> </div> </div> </div> </div> </div>

scholarly journals Drug Binding Dynamics of the Dimeric SARS-CoV-2 Main Protease, Determined by Molecular Dynamics Simulation

2020 ◽  
Author(s):  
Teruhisa S. KOMATSU ◽  
Noriaki Okimoto ◽  
Yohei M. KOYAMA ◽  
Yoshinori HIRANO ◽  
Gentaro MORIMOTO ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Active Site ◽  
Binding Sites ◽  
Complex Structure ◽  
Drug Binding ◽  
Dynamics Simulation ◽  
Trajectory Data ◽  
Main Protease ◽  
Dynamic Sampling

<div> <div> <div> <p>We performed molecular dynamics simulation of the dimeric SARS-CoV-2 (severe acute respiratory syndrome corona virus 2) main protease (Mpro) to examine the binding dynamics of small molecular ligands. Seven HIV inhibitors, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, and tipranavir, were used as the potential lead drugs to investigate access to the drug binding sites in Mpro. The frequently accessed sites on Mpro were classified based on contacts between the ligands and the protein, and the differences in site distributions of the encounter complex were observed among the ligands. All seven ligands showed binding to the active site at least twice in 28 simulations of 200 ns each. We further investigated the variations in the complex structure of the active site with the ligands, using microsecond order simulations. Results revealed a wide variation in the shapes of the binding sites and binding poses of the ligands. Additionally, the C-terminal region of the other chain often interacted with the ligands and the active site. Collectively, these findings indicate the importance of dynamic sampling of protein- ligand complexes and suggest the possibilities of further drug optimisations. <br></p><p><br></p><p><br> </p><div> <div> <div> <p>Raw trajectory data analysed in this paper and movie examples are available at the zenodo repository.<br></p> </div> </div> </div> </div> </div> </div>

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