Investigation of Cu metal nanoparticles with different morphologies to inhibit SARS-CoV-2 main protease and spike glycoprotein using Molecular Docking and Dynamics Simulation

Abstract

Nowadays, considering the spread of the coronavirus as a global threat, scientific research on this virus through simulation has been increasing. In this study, effect of Cu nanocluster on prevention and control of disease transmission was examined using molecular docking and molecular dynamics simulation studies on the SARS-CoV-2 main protease and spike glycoprotein. The cytotoxicity of different shapes of copper NPs and resonance changes of their surface plasmons on inactivation of the coronavirus was examined in order to control replication of coronavirus through copper NPs, active site of protease and spike glycoprotein. The simulations results showed that interactions of SARS-CoV-2 main protease and spike glycoprotein target and cylindrical and conical copper NPs ligands were more efficient than spherical copper NPs.

Keywords: COVID-19; Copper NPs; Molecular Docking; Molecular Dynamics Simulation; Protease and Spike Glycoprotein Inhibitor.

Graphical abstract

Figure 1

a) Cone b) Cylindrical c) Spherical copper NPs molecular structure as Ball and Bond type in position drawn by MVD 6.0.

Figure 2

The energy units of spherical Cu NPs, cylindrical Cu NPs and conical Cu NPs.

Figure 3

The α helices and β strands of a) 6M03 protein (3D) b) 6ZGG protein (3D) are represented as coils (red) and arrows (blue) respectively.) with the selected crystal structure drawn by MOE 2011.

Figure 4

Area of molecular structure of a) 6M03 protein b) 6ZGG protein. The cavities of the targets that interact with the ligand and dock there green color drawn by MVD 6.0

Figure 5

The active sites molecular structures of a) 6M03 protein b) 6ZGG proteins. The docking areas are shown as white and red ball drawn by MOE 2011.

Figure 6

Schematic of the molecular docking between the Copper NPs ligands and the 6M03 receptor along with the pharmacophore and ligand map drawn by MMV 7.0.

Figure 7

Schematic of the molecular docking between the Copper NPs ligands and the 6ZGG receptor along with the pharmacophore and ligand map drawn by MMV 7.0.

Figure 8

Schematic of the molecular docking between the Spherical copper NPs ligand and the 6M03 receptor along with the pharmacophore drawn by MOE 2011.

Figure 9

Schematic of the molecular docking between the Cylindrical Copper NPs ligand and the 6M03 receptor along with the pharmacophore drawn by MOE 2011.

Figure 10

Schematic of the molecular docking between the Cone Copper NPs ligand and the 6M03 receptor along with the pharmacophore and ligand map drawn by MOE 2011.

Figure 11

Schematic of the molecular docking between the Spherical Copper NPs ligand and the 6ZGG receptor along with the pharmacophore and ligand map drawn by MOE 2011.

Figure 12

Schematic of the molecular docking between the Cylindrical Copper NPs ligand and the 6ZGG receptor along with the pharmacophore and ligand map drawn by MOE 2011.

Figure 13

Schematic of the molecular docking between the Conical Copper NPs ligand and the 6ZGG receptor along with the pharmacophore drawn by MOE 2011.

Figure 14

RMSD calculations of NPs Cu (Spherical, Cylindrical and Cone) with (a); 6M03 and (b); 6ZGG.

Figure 15

Schematic of the molecular docking between the Copper NPs ligands and the 6M03 receptor along with the pharmacophore and ligand map drawn by Discovery Studio.

Figure 16

Schematic of the molecular docking between the Copper NPs ligands and the 6ZGG receptor along with the pharmacophore and ligand map drawn by Discovery Studio.

Figure 17

a) The root mean square deviation (RMSD) value and b) RMSF (root mean square fluctuation) of M^pro SARS-COV-2.

Figure 18

a) The root means square deviation (RMSD) value and b) RMSF (root mean square fluctuation) of spike glycoprotein chain A SARS-COV-2 (6ZGG).

Figure 19

Schematic of the molecular redocking Molecular Dynamics between the cylindrical copper NPs ligand and the 6M03 receptor along with the pharmacophore drawn by MVD 6.0.

Figure 20

Schematic of the molecular redocking Molecular Dynamics between the cylindrical copper NPs ligand and the chain A of 6ZGG receptor along with the pharmacophore drawn by MVD 6.0.

Figure 21

Schematic of the molecular redocking Molecular Dynamics between the Cylindrical copper NPs ligand and the 6M03 receptor along with the pharmacophore drawn by MOE 2011

Figure 22

Schematic of the molecular redocking Molecular Dynamics between the cylindrical copper NPs ligand and the chain A of 6ZGG receptor along with the pharmacophore drawn by MOE 2011

Figure 23

Schematic of the molecular redocking Molecular Dynamics between the copper NPs ligands and the 6M03 receptor along with the pharmacophore and ligand map drawn by Discovery Studio.

Figure 24

Schematic of the molecular redocking Molecular Dynamics between the copper NPs ligands and the chain A of 6ZGG along with the pharmacophore and ligand map drawn by Discovery Studio.