Investigation of Molecular Mechanisms in Inhibiting the Function of Spike, Main Protease and Papain Like Protease in Coronavirus Using Simulation and Docking

Aim and

Coronavirus is the causative agent of COVID-19 infectious pneumonia, which was introduced by the World Health Organization in 2020 as a global epidemic. Due to the fact that its inhibitory mechanisms have not been well understood so far, in this article we decided to investigate the inhibitory mechanisms of Spike, Main Protease and Papain-like protease proteins in the coronavirus.

In the present study, all calculations were performed by AutoDock 4.2 (2013), AutoDockTools 4.2 (2013) and Cluspro2.0 (2017). Lamarckchr('39')s genetic algorithm was used to search for protein levels, and 200 were performed in each of the docking models. Finally, the interaction of protein binding and inhibitor compounds and hydrogen and hydrophobic binding was calculated by Poseview and DIMPLOT software.
 

The interaction study showed that the amino acids His163, His164, Gln189, Glu166, Cys145 and Phe140 play a key role in the inhibitory interaction of GC-376 with Mpro protein due to hydrogen bonds. Also, the study of the binding energy of the inhibitor compound to the protein shows that this compound is attached to the inhibitor with a binding energy of -6.36 kcal / mol. The docking results of PLpro complex showed that the amino acids Tyr268, Gln269, and Asp164 play a key role in the interaction of GRL0617 inhibitor with PLpro protein due to hydrogen bonds and the binding energy of the inhibitor compound to PLpro protein was -9.69. Finally, the study of the interactions of Spike protein and LCB1 peptide using Cluspro and DIMPLOT software showed that there are several hydrophobic and polar interactions between different amino acids of these two compounds, the most important of which can be He noted the interaction of the amino acid Tyr489 in the Spike protein with the amino acids Leu6 and Gln7 in the inhibitory peptide.
 

The results of this study showed that the inhibitory compounds presented in this article can well inhibit vital proteins important in coronavirus due to polar and hydrophobic interactions.