scholarly journals Penambatan Molekuler dan Simulasi Dinamika Molekuler Senyawa Dari Genus Nigella Terhadap Penghambatan Aktivitas Enzim Protease HIV-1

2020 ◽  
Vol 6 (1) ◽  
pp. 132-140
Author(s):  
Muhammad Sulaiman Zubair ◽  
Saipul Maulana ◽  
Alwiyah Mukaddas
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Amino Acid ◽  
Active Site ◽  
Inhibitory Activity ◽  
Nigella Sativa ◽  
Dynamics Simulation ◽  
Protease Enzyme ◽  
Enzyme Model ◽  
Hiv 1

Nigella plant genus has potential as anti-HIV. One species of Nigella, Nigella sativa has been reported to have HIV-1 protease enzyme inhibitory activity. This research aims to determine the compounds of the Nigella genus that have activity as HIV-1 protease enzyme inhibitory activity through molecular docking method by Autodock Vina and to compare interaction stability through molecular dynamics simulations by AMBER. The metabolite of the Nigella genus was obtained from the KnapSack website, and enzyme model was obtained from the Protein Data Bank (3NU3). The results of molecular docking found the lowest affinity energy of Nigella compound is Nigellidine 4-O-sulfite (-13.4 kcal/mol). Meanwhile, the affinity energy of the ligand native (Amprenavir) was -12.1 kcal/mol. The lowest affinity energy of Nigellidine 4-O-sulfite might be predicted to have potency as an HIV-1 Protease inhibitor. Molecular dynamics simulation showed Root Mean Square Fluctuation (RMSF) value of Nigellidine 4-O-sulfite with the amino acid active site is 0.4064 Å for ASP:25 and 0.5667 Å for ASP: 125. Whereas RMSF ligand native with the amino acid active site, ASP: 25 is 0.3647 Å and ASP: 125 is 0.3639 Å. The higher RMSF value of Nigellidine 4-O-sulfite describes the lower interaction stability than the ligand native.

scholarly journals Identification of Natural Inhibitors Against SARS-CoV-2 Drugable Targets Using Molecular Docking, Molecular Dynamics Simulation, and MM-PBSA Approach

2021 ◽  
Vol 11 ◽  
Author(s):  
Prem Prakash Kushwaha ◽  
Atul Kumar Singh ◽  
Tanya Bansal ◽  
Akansha Yadav ◽  
Kumari Sunita Prajapati ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Molecular Docking ◽  
Active Site ◽  
Md Simulation ◽  
Dynamics Simulation ◽  
Stable Complex ◽  
Kcal Mole ◽  
Hydrogen Bond Formation ◽  
Docking Score

The present study explores the SARS-CoV-2 drugable target inhibition efficacy of phytochemicals from Indian medicinal plants using molecular docking, molecular dynamics (MD) simulation, and MM-PBSA analysis. A total of 130 phytochemicals were screened against SARS-CoV-2 Spike (S)-protein, RNA-dependent RNA polymerase (RdRp), and Main protease (Mpro). Result of molecular docking showed that Isoquercetin potentially binds with the active site/protein binding site of the Spike, RdRP, and Mpro targets with a docking score of -8.22, -6.86, and -9.73 kcal/mole, respectively. Further, MS 3, 7-Hydroxyaloin B, 10-Hydroxyaloin A, showed -9.57, -7.07, -8.57 kcal/mole docking score against Spike, RdRP, and Mpro targets respectively. The MD simulation was performed to study the favorable confirmation and energetically stable complex formation ability of Isoquercetin and 10-Hydroxyaloin A phytochemicals in Mpro-unbound/ligand bound/standard inhibitor bound system. The parameters such as RMSD, RMSF, Rg, SASA, Hydrogen-bond formation, energy landscape, principal component analysis showed that the lead phytochemicals form stable and energetically stabilized complex with the target protein. Further, MM-PBSA analysis was performed to compare the Gibbs free energy of the Mpro-ligand bound and standard inhibitor bound complexes. The analysis revealed that the His-41, Cys145, Met49, and Leu27 amino acid residues were majorly responsible for the lower free energy of the complex. Drug likeness and physiochemical properties of the test compounds showed satisfactory results. Taken together, the study concludes that that the Isoquercetin and 10-Hydroxyaloin A phytochemical possess significant efficacy to bind SARS-Cov-2 Mpro active site. The study necessitates further in vitro and in vivo experimental validation of these lead phytochemicals to assess their anti-SARS-CoV-2 potential.

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.

Three Major Phosphoacceptor Sites in HIV-1 Capsid Protein Enhances its Structural Stability and Resistance Against the Inhibitor: Explication Through Molecular Dynamics Simulation, Molecular Docking and DFT Analysis

2020 ◽  
Vol 23 (1) ◽  
pp. 41-54 ◽  
Author(s):  
Nouman Rasool ◽  
Waqar Hussain
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Capsid Protein ◽  
Structural Stability ◽  
Md Simulations ◽  
Host Cells ◽  
Dynamics Simulation ◽  
Maximum Stability ◽  
The Stability ◽  
Hiv 1

Background: Human Immunodeficiency Virus 1 (HIV-1) is a lentivirus, which causes various HIV-associated infections. The HIV-1 core dissociation is essential for viral cDNA synthesis and phosphorylation of HIV-1 capsid protein (HIV-1 CA) plays an important role in it. Objective: The aim of this study was to explicate the role of three phosphoserine sites i.e. Ser109, Ser149 and Ser178 in the structural stability of HIV-1 CA, and it’s binding with GS-CA1, a novel potent inhibitor. Method: Eight complexes were analyzed and Molecular Dynamics (MD) simulations were performed to observe the stability of HIV-1 CA in the presence and absence of phosphorylation of serine residues at four different temperatures i.e. 300K, 325K, 340K and 350K, along with molecular docking and DFT analysis. Results: The structures showed maximum stability in the presence of phosphorylated serine residue. However, GS-CA1 docked most strongly with the native structure of HIV-1 CA i.e. binding affinity was -8.5 kcal/mol (Ki = 0.579 µM). Conclusion: These results suggest that the phosphorylation of these three serine residues weakens the binding of GS-CA1 with CA and casts derogatory effect on inhibition potential of this inhibitor, but it supports the stability of HIV-1 CA structure that can enhance regulation and replication of HIV-1 in host cells.

Synthesis, Molecular Docking and Molecular Dynamics Simulation of 2-thioxothiazolidin-4-one derivatives against Gp41

2020 ◽  
Vol 18 ◽  
Author(s):  
Nahid Tamiz ◽  
Tahereh Mostashari-Rad ◽  
Aylar Najafipour ◽  
Sandra Claes ◽  
Dominique Schols ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Biological Activities ◽  
Dynamics Simulation ◽  
Heptad Repeat ◽  
Chemical Interactions ◽  
Chemical Structures ◽  
In Silico Studies ◽  
Anti Hiv ◽  
Hiv 1

Introduction: Gp41 and its conserved hydrophobic groove on the N-terminal heptad repeat region are of attractive targets in the design of HIV-1 entry inhibitors. Linearly extended molecules have shown potent anti-HIV-1 activity for their effective interactions with the gp41 binding pocket. Rhodanine ring attached to substituted pyrrole or furan rings has been proved a preferred moiety to be inserted inside the molecular structure of the gp41 inhibitors. Objectives: Based on the previous findings we are going to describe some rhodanine derivatives in which a substituted imidazole ring is introduced in place of the pyrrole or furan rings. The compounds’ flexibility is increased by inserting methylene groups inside the main scaffold. Methods: Molecular docking and molecular dynamics simulations approaches were exploited to investigate the chemical interactions and the stability of the designed ligands-gp41 complex. All compounds were synthesized and their chemical structures were elucidated by 1HNMR, 13CNMR, FTIR and Mass spectroscopy. Biological activities of the compounds against HIV-1 and HIV-2 and their cellular toxicities against the T-lymphocyte (MT-4) cell line were determined. Results: All the designed compounds showed proper and stable chemical interactions with gp41 according to the in silico studies. The results of the biological tests proved none of the compounds active against HIV-1 replication in cell cultures. Conclusion: Since all the studied compounds were potently toxic for the host cell; it was therefore not possible to assess their anti-HIV activities.

scholarly journals Exploring the Potency of Nigella sativa Seed in Inhibiting SARS-CoV-2 Main Protease Using Molecular Docking and Molecular Dynamics Simulations

2021 ◽  
Vol 21 (5) ◽  
pp. 1252
Author(s):  
Ari Hardianto ◽  
Muhammad Yusuf ◽  
Ika Wiani Hidayat ◽  
Safri Ishmayana ◽  
Ukun Mochammad Syukur Soedjanaatmadja
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulations ◽  
Global Economy ◽  
Nigella Sativa ◽  
Scientific Information ◽  
Dynamics Simulation ◽  
Lipinski’S Rule ◽  
Main Protease ◽  
Dynamics Simulations

Coronavirus disease (COVID-19) is a pandemic burdening the global economy. It is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Black cumin (Nigella sativa) seed may contain antivirals for the disease since it was reported to inhibit the human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Main protease (Mpro) is a vital protein for viral replication and a promising target for COVID-19 drug development. Hence, in this study, we intended to uncover the potency of N. sativa seed as the natural source of inhibitors for SARS-CoV-2 Mpro. We collected secondary metabolites in N. sativa seed through a literature search and employed Lipinski’s rule of five as the initial filter. Subsequently, virtual screening campaigns using a molecular docking method were performed, with N3 inhibitor and leupeptin as reference ligands. The top hits were analyzed further using a molecular dynamics simulation approach. Molecular dynamics simulations showed that binding affinities of nigellamine A2 and A3 to Mpro are comparable to that of leupeptin, with median values of -43.9 and -36.2 kcal mol–1, respectively. Ultimately, this study provides scientific information regarding N. sativa seeds’ potency against COVID-19 and helps direct further wet experiments.

scholarly journals Comparative analysis of the unbinding pathways of antiviral drug Indinavir from HIV and HTLV1 proteases by supervised molecular dynamics simulation

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257916
Author(s):  
Farzin Sohraby ◽  
Hassan Aryapour
Keyword(s):  
Active Site ◽  
Inhibitory Activity ◽  
Antiviral Drug ◽  
Dynamics Simulation ◽  
Stacking Interactions ◽  
Aromatic Residues ◽  
Efficacious Treatment ◽  
The Stability ◽  
Flap Region ◽  
Hiv 1

Determining the unbinding pathways of potential small molecule compounds from their target proteins is of great significance for designing efficacious treatment solutions. One of these potential compounds is the approved HIV-1 protease inhibitor, Indinavir, which has a weak effect on the HTLV-1 protease. In this work, by employing the SuMD method, we reconstructed the unbinding pathways of Indinavir from HIV and HTLV-1 proteases to compare and understand the mechanism of the unbinding and to discover the reasons for the lack of inhibitory activity of Indinavir against the HTLV-1 protease. We achieved multiple unbinding events from both HIV and HTLV-1 proteases in which the RMSD values of Indinavir reached over 40 Å. Also, we found that the mobility and fluctuations of the flap region are higher in the HTLV-1 protease, making the drug less stable. We realized that critically positioned aromatic residues such as Trp98/Trp98′ and Phe67/Phe67′ in the HTLV-1 protease could make strong π-Stacking interactions with Indinavir in the unbinding pathway, which are unfavorable for the stability of Indinavir in the active site. The details found in this study can make a reasonable explanation for the lack of inhibitory activity of this drug against HTLV-1 protease. We believe the details discovered in this work can help design more effective and selective inhibitors for the HTLV-1 protease.

scholarly journals Qualitative and quantitative analysis of anti-viral compounds against SARS-CoV-2 protease enzyme by molecular dynamics simulation and MM/PBSA method

2021 ◽  
Author(s):  
Saghi Sepehri ◽  
Niloufar Hashemidanesh ◽  
Karim Mahnam ◽  
Hila Asham
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Quantitative Analysis ◽  
Molecular Dynamics Simulation ◽  
Binding Energy ◽  
Active Site ◽  
Dynamics Simulation ◽  
Qualitative And Quantitative Analysis ◽  
Qualitative And Quantitative ◽  
In Silico Studies

Background: A significant worry for global public health is the international spread of the coronavirus disease-19 triggered through the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, an attempt was performed to qualitative and quantitative analysis of a series of compounds against SARS-CoV-2 main protease (M<[pro]) by in silico studies. Methods: About one hundred anti-viral compounds were collected from DrugBank database. In the second stage, molecular docking simulation was carried out to identify interactions of the molecules with the key residues in the M<[pro] active site. Finally, the molecular dynamics simulation of four top-ranked compounds and X77 as Co-crystal ligand were investigated. Results:Based on molecular docking studies, four compounds DB00224, DB00220, DB01232 and DB08873 exhibited the best results among compounds against M<[pro] enzyme. Additionally, molecular dynamic simulation and free binding energy were accomplished to compute the interaction energies and stability of the top-ranked compounds at the active site. The binding energy portions of the compounds into the enzyme active site exposed that Van der Waals and non-polar interactions were fundamental factors in the molecule binding. The ligand connections were steadied via hydrophobic interactions and several key hydrogen bonds especially with Glu166 and His41 residues into the active site. Conclusion: According to calculations of docking and MD, it was observed that the active site is mostly hydrophobic, where the value of the ∆Evdw is higher than that of the ∆Eele. Additionally, the results showed the steady of selected ligands binding with SARS-CoV-2 M<[pro] active site.

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