scholarly journals 1,2,4 triazolo[1,5-a] pyrimidin-7-ones as novel SARS-CoV-2 Main protease inhibitors: In silico screening and molecular dynamics simulation of potential COVID-19 drug candidates

2020 ◽  
Vol 267 ◽  
pp. 106478
Author(s):  
Kuppuswamy Kavitha ◽  
Subramaniam Sivakumar ◽  
Balasubramanian Ramesh
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Protease Inhibitors ◽  
In Silico ◽  
Dynamics Simulation ◽  
In Silico Screening ◽  
Drug Candidates ◽  
Main Protease

scholarly journals A computational biology approach for the identification of potential SARS-CoV-2 main protease inhibitors from natural essential oil compounds.

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 1313
Author(s):  
Rizone Al Hasib ◽  
Md. Chayan Ali ◽  
Md. Shahedur Rahman ◽  
Md. Mafizur Rahman ◽  
Fee Faysal Ahmed ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Essential Oil ◽  
New Drugs ◽  
Dynamics Simulation ◽  
World Health ◽  
Drug Candidates ◽  
Main Protease ◽  
Essential Oil Compounds

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has fomented a climate of fear worldwide due to its rapidly spreading nature, and high mortality rate. The World Health Organization (WHO) declared it as a global pandemic on 11th March, 2020. Many endeavors have been made to find appropriate medications to restrain the SARS CoV-2 infection from spreading but there is no specific antiviral therapy to date. However, a computer-aided drug design approach can be an alternative to identify probable drug candidates within a short time. SARS-CoV-2 main protease is a proven drug target, and it plays a pivotal role in viral replication and transcription. Methods: In this study, we identified a total of 114 essential oil compounds as a feasible anti-SARS-CoV-2 agent from several online reservoirs. These compounds were screened by incorporating ADMET profiling, molecular docking, and 50 ns of molecular dynamics simulation to identify potential drug candidates against the SARS-CoV-2 main protease. The crystallized SARS-CoV-2 main protease structure was collected from the RCSB PDB database (PDB ID 6LU7). Results: According to the results of the ADMET study, none of the compounds have any side effects that could reduce their druglikeness or pharmacokinetic properties. Out of 114 compounds, we selected bisabololoxide B, eremanthin, and leptospermone as our top drug candidates based on their higher binding affinity scores, and strong interaction with the Cys 145-His 41 catalytic dyad. Finally, the molecular dynamics simulation was implemented to evaluate the structural stability of the ligand-receptor complex. MD simulations disclosed that all the hits showed conformational stability compared to the positive control α-ketoamide. Conclusions: Our study showed that the top three hits might work as potential anti-SARS-CoV-2 agents, which can pave the way for discovering new drugs, but for experimental validation, they will require more in vivo trials.

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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