scholarly journals Exploring the Regulatory Function of the N ‐terminal Domain of SARS‐CoV‐2 Spike Protein through Molecular Dynamics Simulation

2021 ◽  
pp. 2100152
Author(s):  
Yao Li ◽  
Tong Wang ◽  
Juanrong Zhang ◽  
Bin Shao ◽  
Haipeng Gong ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Dynamics Simulation ◽  
Spike Protein ◽  
Regulatory Function ◽  
Terminal Domain

scholarly journals Investigation of the effect of Hydroxychloroquine, Remdesivir, Oseltamivir and some home remedies in the light of Molecular Dynamics Simulation

2020 ◽  
Author(s):  
Keka Talukdar
Keyword(s):  
Molecular Dynamics ◽  
Clinical Trial ◽  
Computer Simulation ◽  
Molecular Dynamics Simulation ◽  
Human Cell ◽  
Physical Modeling ◽  
Chemical Species ◽  
Dynamics Simulation ◽  
Spike Protein ◽  
Simulation Based

Modeling and simulation is another way of finding the interaction between different drugs and chemical species with human cell. Preliminary studies before clinical trial involve computer simulation based on the physical modeling so that clinical trial can be made easier. In many aspects of drug developing, simulation is an essential tool. Here molecular dynamics simulation is performed for the interaction of the spike protein of Covid-19 virus and some of the recently used drugs. Also, the effect of caffeine, theanine, nicotine etc on the virus is found by simulation

scholarly journals Molecular dynamics simulation and docking studies reveal NF-κB as a promising therapeutic drug target for COVID-19

2021 ◽  
Author(s):  
Shaban Ahmad ◽  
Piyush Bhanu ◽  
Jitendra Kumar ◽  
Ravi Kant Pathak ◽  
Dharmendra Mallick ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Protein Structures ◽  
Drug Repurposing ◽  
Docking Studies ◽  
Dynamics Simulation ◽  
Spike Protein ◽  
Drug Candidate ◽  
Therapeutic Drug ◽  
Ligand Complex

Abstract Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is rampant worldwide and is a deadly disease for humans. Our current work emphasizes on molecular dynamics simulation (MDS) targeting nuclear factor-kappa B (NF-κB), the well-known human transcription factor controlling innate and adaptive immunity, to understand its mechanism of action during COVID-19 in humans. NF-κB was interacted with the SARS-CoV-2 spike protein in an in silico MDS experiment, revealing the NF-κB site at which the SARS-CoV-2 spike protein interacts. We screened some known drugs via docking studies on NF-κB used as a receptor. The MDS software Schrodinger generated more than 2000 complexes from these compounds and using the SMILES format of these complexes, 243 structures were extracted and 411 conformers were generated. The drug used as a ligand that docked with NF-κB with the best docking score and binding affinity was Sulindac sodium as its trade name. Furthermore, RMSF data of sulindac sodium and NF-κB displayed minimal fluctuations in the protein structures, and the protein-ligand complex had reduced flexibility. Sulindac sodium is hence suggested as a suitable drug candidate for repurposing in clinical trials for SARS-CoV-2 infections. This drug potently blocked the spike protein’s interaction with NF-κB by inducing a conformational change in the latter. Arguably, NF-κB inaction is desired to have normal immunity and can possibly be retained using proposed drug. This work provides a significant lead for drug repurposing to combat SARS-CoV-2 and its various mutant forms and reveals new approach for controlling SARS-CoV-2-induced disease.

scholarly journals Molecular Dynamics Simulation Studies reveal NF-kappa B as a strong therapeutic drug target for COVID19

2021 ◽  
Author(s):  
Shaban Ahmad ◽  
Piyush Bhanu ◽  
Jitendra Kumar ◽  
Ravi Kant Pathak ◽  
Dharmendra Mallick ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Previous History ◽  
Dynamics Simulation ◽  
Spike Protein ◽  
Therapeutic Drug ◽  
Molecular Formula ◽  
Dependent Manner ◽  
Human Beings ◽  
Nf Kappa B

Abstract COVID19 caused due to SARS-CoV2, is rampant world wide and human beings with previous history of other major ailments are increasingly at risk of mortality due to this disease in a predetermined manner. Countries have developed vaccines claiming to counter the SARS-CoV2 virus to a great extent. However, convincing evidences are lacking in this regard as mortality post-vaccination is not uncommon, though exact reason of the morbidity is unknown yet. Our current work primarily focuses on molecular dynamics simulation (MDS) targeting NF-kappa B (NF-κB), the well-known human transcription factor that controls innate and adaptive immunity, with an aim to understand its mechanism of action under COVID19 virus load in humans. To understand this, NF-κB was made to interact with spike protein of SARS-CoV2 in an in silico experimental design employing Molecular Dynamics Simulation (MDS) studies. Some interesting findings were made revealing the site of NF-κB at which spike protein of SARS-CoV2 interacts. We attempted to subject some known drugs to be screened based on their docking studies with nuclear factor kappa B (NF-κB) to MDS studies. MDS Software Schrodinger generated more than 2000 complexes from these compounds and structure exportation was hence not possible. Using the SMILE IDs of 243 ligands, we generated a total of 411 confirmers employing the ligand preparation wizard. These were docked at the active site using the Glide program. A drug named Sulindac sodium (Molecular Formula C20H16FO3S) was found having ability to target NF-κB and can be repurposed for controlling SARS-CoV2 based on the positive results obtained during MDS analysis. This drug showed potency to block the spike protein’s interaction with NF-κB by bringing about a conformational change in the latter. It is hypothesized presently that NF-κB activation that leads to migration of this molecule to nucleus for gene transcription and immunity inhibition, is triggered either directly by binding of spike protein to NF-κB or spike protein’s interaction with some pathway kinase that phosphorylates IκBs, another molecule essential to get released from the NF-κB-IκB complex, to set NF-κB free to get translocated to nucleus for action. Arguably, NF-κB inaction is desired to allow normal immunity to become functional and can possibly be retained using our repurposed drug-based interaction. This work provides a significant lead in the knowledge on drug development for tackling SARS-CoV2 and its various mutant forms by blocking the functioning of the virus in a NF-κB-dependent manner in host tissues and opens up new vistas in controlling critical state SARS-CoV2 disease.

Homology Modeling and Evaluation of Sars-Cov-2 Spike Protein Mutant

2021 ◽  
Vol 6 (4) ◽  
pp. 38-55
Author(s):  
Hima Vyshnavi ◽  
Aswin Mohan ◽  
Shahanas Naisam ◽  
Suvanish Kumar ◽  
Nidhin Sreekumar
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Antiviral Drug ◽  
Dynamics Simulation ◽  
Spike Protein ◽  
Structure Modeling ◽  
Ramachandran Plot ◽  
Global Pandemic ◽  
The Stability

Severe acute respiratory syndrome coronavirus 2 (SARS‐Cov-2), a global pandemic, affected the world, increasing every day. A mutated variant D614G, showing more virulence and transmission, was studied for forecasting the emergence of more virulent and pathogenic viral strains. This study focuses on structure modeling and validation. Characterization of proteins homologous to wild spike protein was done, and homology models of the mutated variant were modeled using these proteins. Validation of models was done using Ramachandran plot and ERRAT plot. Molecular dynamics simulation was used to validate the stability of the models, and binding affinity of these models were estimated by molecular docking with an approved antiviral drug. Docked complexes were studied and the best model was selected. Molecular dynamics simulation was used to estimate the stability of the docked complex. The model of 6VXX, a homologous of wild spike protein, was found to be stable with the interaction of the antiviral drug from this study.

scholarly journals Identification of Potential SARS-CoV-2 Main Protease and Spike Protein Inhibitors from the Genus Aloe: An In Silico Study for Drug Development

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1767
Author(s):  
Mohamed E. Abouelela ◽  
Hamdy K. Assaf ◽  
Reda A. Abdelhamid ◽  
Ehab S. Elkhyat ◽  
Ahmed M. Sayed ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Drug Development ◽  
Root Mean Square ◽  
In Silico ◽  
Dynamics Simulation ◽  
Spike Protein ◽  
Energy Calculation ◽  
Mean Square ◽  
Main Protease

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) disease is a global rapidly spreading virus showing very high rates of complications and mortality. Till now, there is no effective specific treatment for the disease. Aloe is a rich source of isolated phytoconstituents that have an enormous range of biological activities. Since there are no available experimental techniques to examine these compounds for antiviral activity against SARS-CoV-2, we employed an in silico approach involving molecular docking, dynamics simulation, and binding free energy calculation using SARS-CoV-2 essential proteins as main protease and spike protein to identify lead compounds from Aloe that may help in novel drug discovery. Results retrieved from docking and molecular dynamics simulation suggested a number of promising inhibitors from Aloe. Root mean square deviation (RMSD) and root mean square fluctuation (RMSF) calculations indicated that compounds 132, 134, and 159 were the best scoring compounds against main protease, while compounds 115, 120, and 131 were the best scoring ones against spike glycoprotein. Compounds 120 and 131 were able to achieve significant stability and binding free energies during molecular dynamics simulation. In addition, the highest scoring compounds were investigated for their pharmacokinetic properties and drug-likeness. The Aloe compounds are promising active phytoconstituents for drug development for SARS-CoV-2.

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