scholarly journals Exploring the Association Between Sialic Acid and SARS-CoV-2 Spike Protein Through a Molecular Dynamics-Based Approach

2021 ◽  
Vol 2 ◽  
Author(s):  
Leonardo Bò ◽  
Mattia Miotto ◽  
Lorenzo Di Rienzo ◽  
Edoardo Milanetti ◽  
Giancarlo Ruocco
Keyword(s):  
Molecular Dynamics ◽  
Sialic Acid ◽  
Structural Characteristics ◽  
Principal Component ◽  
Dynamics Simulation ◽  
Spike Protein ◽  
Binding Effect ◽  
Terminal Domain ◽  
Correlated Motion ◽  
The Stability

Recent experimental evidence demonstrated the capability of SARS-CoV-2 Spike protein to bind sialic acid molecules, which was a trait not present in SARS-CoV and could shed light on the molecular mechanism used by the virus for the cell invasion. This peculiar feature has been successfully predicted by in-silico studies comparing the sequence and structural characteristics that SARS-CoV-2 shares with other sialic acid-binding viruses, like MERS-CoV. Even if the region of the binding has been identified in the N-terminal domain of Spike protein, so far no comprehensive analyses have been carried out on the spike-sialic acid conformations once in the complex. Here, we addressed this aspect performing an extensive molecular dynamics simulation of a system composed of the N-terminal domain of the spike protein and a sialic acid molecule. We observed several short-lived binding events, reconnecting to the avidic nature of the binding, interestingly occurring in the surface Spike region where several insertions are present with respect to the SARS-CoV sequence. Characterizing the bound configurations via a clustering analysis on the Principal Component of the motion, we identified different possible binding conformations and discussed their dynamic and structural properties. In particular, we analyze the correlated motion between the binding residues and the binding effect on the stability of atomic fluctuation, thus proposing regions with high binding propensity with sialic acid.

scholarly journals Molecular Mechanism of Clinically Oriented Drug Famotidine with the Identified Potential Target of SARS-CoV-2

2020 ◽  
Author(s):  
Parth Sarthi Sen Gupta ◽  
Satyaranjan Biswal ◽  
Dipankar Singha ◽  
Malay Kumar Rana
Keyword(s):  
Molecular Dynamics ◽  
Principal Component ◽  
Dynamics Simulation ◽  
Radius Of Gyration ◽  
Binding Mechanism ◽  
Protein Targets ◽  
Potential Target ◽  
The Usa ◽  
The Stability ◽  
Novel Coronavirus

<p>Due to the current pandemic nature, severity, and rapid spread of COVID-19, there is eminent need to identify potential therapeutics to inhibit the novel coronavirus. In the quest, scientists from the USA had reported that the use of Famotidine in patients was associated with improved clinical outcomes and a reduced risk of intubation or death from COVID-19. However, the exact mode of action, the binding mechanism, and precise <a>COVID-19 </a>molecular target with which Famotidine interacts are yet to be ascertained. Here, 12 different COVID-19 protein targets have been screened against Famotidine employing molecular docking and molecular dynamics simulation. This reveals, among all the targets, the Papain-like protease (PLpro) as the potential target having the strongest affinity to Famotidine estimated to be of -7.9 kcal/mol with three hydrogen bonds. Tyrosine residue in the 268<sup>th</sup> position in the binding site seems to be very crucial for the stability of the PLpro-Famotidine complex, giving rise to multiple interactions such as hydrogen bonding as well as π-Sulfur. While the post-molecular dynamics (MD) analyses such as the root-mean-square deviation (RMSD) and fluctuation (RMSF), the radius of gyration (R<sub>g</sub>), and the principal component analysis (PCA) affirm the stability of the complex providing an insight into the binding mechanism, the identification of a valid target PLpro of SARS-COV-2 for Famotidine would help understand its action, further development, and experimental exploration.</p>

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 Molecular Mechanism of Clinically Oriented Drug Famotidine with the Identified Potential Target of SARS-CoV-2

2020 ◽  
Author(s):  
Parth Sarthi Sen Gupta ◽  
Satyaranjan Biswal ◽  
Dipankar Singha ◽  
Malay Kumar Rana
Keyword(s):  
Molecular Dynamics ◽  
Principal Component ◽  
Dynamics Simulation ◽  
Radius Of Gyration ◽  
Binding Mechanism ◽  
Protein Targets ◽  
Potential Target ◽  
The Usa ◽  
The Stability ◽  
Novel Coronavirus

<p>Due to the current pandemic nature, severity, and rapid spread of COVID-19, there is eminent need to identify potential therapeutics to inhibit the novel coronavirus. In the quest, scientists from the USA had reported that the use of Famotidine in patients was associated with improved clinical outcomes and a reduced risk of intubation or death from COVID-19. However, the exact mode of action, the binding mechanism, and precise <a>COVID-19 </a>molecular target with which Famotidine interacts are yet to be ascertained. Here, 12 different COVID-19 protein targets have been screened against Famotidine employing molecular docking and molecular dynamics simulation. This reveals, among all the targets, the Papain-like protease (PLpro) as the potential target having the strongest affinity to Famotidine estimated to be of -7.9 kcal/mol with three hydrogen bonds. Tyrosine residue in the 268<sup>th</sup> position in the binding site seems to be very crucial for the stability of the PLpro-Famotidine complex, giving rise to multiple interactions such as hydrogen bonding as well as π-Sulfur. While the post-molecular dynamics (MD) analyses such as the root-mean-square deviation (RMSD) and fluctuation (RMSF), the radius of gyration (R<sub>g</sub>), and the principal component analysis (PCA) affirm the stability of the complex providing an insight into the binding mechanism, the identification of a valid target PLpro of SARS-COV-2 for Famotidine would help understand its action, further development, and experimental exploration.</p>

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

Virtual Screening of Phyto Chemicals Against SARS-CoV-2 Targets

2021 ◽  
Vol 6 (3) ◽  
pp. 61-76
Author(s):  
Shahanas Naisam ◽  
Vidhya V. S. ◽  
Suvanish Kumar ◽  
Nidhin Sreekumar
Keyword(s):  
Dynamics Simulation ◽  
Spike Protein ◽  
Ligand Interaction ◽  
Docking Analysis ◽  
Drug Molecules ◽  
In Vivo Analysis ◽  
Protein Ligand Interaction ◽  
The Stability ◽  
3Cl Protease

The COVID-19 pandemic wave has recommenced and is spreading like wildfire across the globe. The well-reported antiviral potency of phyto compounds could offer potential drug molecules for the current predicament. The present study analyses the molecular interaction of selected phyto compounds and SARS-CoV-2 molecular target proteins, namely spike protein, RNA-dependent RNA polymerase, 3C-like proteases, and papain-like protease. Ten newly modeled ligands were also considered for the study. Molecular docking analysis was carried out independently using MOE, AutoDock Vina, Schrodinger-Glide, and the stability of protein-ligand interaction was validated through molecular dynamics simulation. Petunidin interacts with spike protein resulting in a good Gscore, binding energy, and H-bond interaction. Also, alions, letestuianin-A, (+)-pinitol show better interaction with RdRp, 3CL-protease, and papain-like protease, respectively. The presented work screens through 2314 ligands to yield top-ranked molecules which could be taken up to develop potential lead molecules via in-vivo analysis.

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