Effect of Nano-Perovskite Structure on Suppressing the SARS-CoV-2 Infection

By Megan Craig, M.Sc.Nov 4 2021

Nanostructures are widely utilized in therapeutic approaches. New research, published in Informatics in Medicine Unlocked employs perovskite nanostructures as a suppression agent for COVID-19 for the first time

Image Credit: peterschreiber.media/Shutterstock.com

The COVID-19 global pandemic, caused by SARS-CoV-2, or coronavirus, started in early 2020 and became dominant in many countries. Millions of people are affected by COVID-19 globally, with pathologies varying from mild respiratory symptoms to acute respiratory distress syndrome (ARDS) and even death. The most common symptoms include headache, fatigue, fever, and cough.

The genome sequence of SARS-CoV-2 was determined, revealing 20 different proteins in the SARS-CoV-2 structure, aiding identification of infection mechanisms. Spike glycoprotein, a trimeric protein that attaches to the cell through angiotensin-converting enzyme 2 (ACE2), is one such protein. 

Numerous nanostructures have been incorporated into therapeutic applications, including perovskites. These nanomaterials are notably used in medicine, such as photo-medicine and bioelectric implants.

Methodology

Researchers simulated the spike proteins that encounter a specific perovskite structure (SrTiO₃, CaTiO₃, BaTiO₃) before ACE2. The effects of these perovskite structures on the deactivation of a spike protein were examined by employing coarse-grained MD simulations (CGMD).

The study employs CGMD in which small groups of atoms are assumed to be a single unit facilitating the investigation of larger timescales. This process is mainly used for polymeric chains materials. The researchers carried out molecular simulations on all atoms. CGMD and docking were conducted to test the interaction between the S protein of COVID-19 and the coarse PD of ACE2. Figure 1 shows the distorting in the structure of the spike protein.

Figure 1. The process of encountering the spike protein with BaTiO₃, CaTiO₃, and SrTiO₃ nanostructure in 0 ns, 1750 ns, and 3000 ns. The distorted spike protein then collides with the ACE2. Image Credit: Khedri, M., et al., 2021.

Simulation Details

MD simulations and data analyses were carried out with GROMACS software, and the energy was calculated by employing the molecular mechanics Poisson-Boltzmann surface area (MMPBSA) computational package.

The spike protein structure and ACE2 were accessed from RSCB, while the perovskite structures were designed via Avogadro software. This software was also used to develop the dimensions of the box and add the molecules and the solvent (the solvent is water to represent aqueous media.

Molecular Docking

The study used AutoDock_vina_1_1_2_linux_x86 for docking the simulation. The gasteiger charge and polar hydrogen were applied through the AutoDock Tool-1.5.6 to the SARS-CoV-2 RBD pdb and ACE2 pdb file, respectively.

Results

Energy

The nanostructure’s power to deform or distort the spike protein is shown by the intermolecular interaction energy. The energy between the nanostructures with spike protein has been calculated to restrain the S protein from penetrating through the ACE2 cell channel. Figure 2 depicts that both van der Waals (VdW) and the S protein’s electrostatic energy levels in the presence of BaTiO₃, CaTiO₃, and SrTiO₃ nanostructures was decreased.

Figure 2. Electrostatic and van der Waals energy levels for Spike protein in direct contact with ACE2 and in the presence of BaTiO₃, CaTiO₃, and SrTiO₃ nanostructures. Image Credit: Khedri, M., et al., 2021.

Upon exposure of the S protein to nano-perovskite structures, the absolute value of energy for re-docking of S protein and PD from ACE2 decreased significantly for all of the structures. The study details the average of the vital molecular analyzes (Table 1) carried out.

Table 1. The total energy, Rg, and average SASA of the spike protein encountered both ACE2 and perovskite nanostructures. Source: Khedri, M., et al., 2021.

Radius of Gyration

The radius of gyration details the compactness of the structure as a function of time. The results of the radius of gyration analyses in the presence of BaTiO₃, CaTiO₃, and SrTiO₃ nanostructures to decrease the radius of gyration by contacting three nano-perovskite structures is shown in Figure 3.

Figure 3. The radius of gyration for BaTiO₃, CaTiO₃, and SrTiO₃ encountering spike protein. Image Credit: Khedri, M., et al., 2021.

RMSD and RMSF

RMSD demonstrates the flexibility of an atom to depart the S protein. The average distance between a certain spike protein and ACE2 in the presence and absence of perovskite nanostructure is shown in Figure 4a.

The average RMSD value between the S protein and ACE2 is higher than the S protein and ACE2 in the presence of perovskite nanostructure. A higher RMSD value indicates greater flexibility in the particle's movements due to thermal fluctuations.

Figure 4. (a) RMSD and (b) RMSF for spike protein with and without BaTiO₃, CaTiO₃, and SrTiO₃ nanostructures. Image Credit: Khedri, M., et al., 2021.

RMSF is the displacement in a single atom or a molecular structure of a reference atom or structure. Figure 4 b shows the RMSF value for the analyzed perovskite structures.

SASA

SASA defines the capacity of a material in an aqueous media to be surrounded by water molecules Figure 5 shows the SASA value of various nanostructures for adsorption of the spike protein.

Figure 5. SASA of BaTiO₃, CaTiO₃, and SrTiO₃ for adsorption of the spike protein. Image Credit: Khedri, M., et al., 2021.

Number of H-Bonds

Figure 6 depicts the number of intermolecular hydrogen bonds for the analyzed structures. During the absence of the perovskite nanostructures, hydrogen bonds are around 40, while Nano-perovskite decreases this value. 

Figure 6. The number of hydrogen bonds between spike protein and ACE2 in the presence and absence of BaTiO₃, CaTiO₃, and SrTiO₃ nanostructures. Image Credit: Khedri, M., et al., 2021.

Distribution of Secondary Structure (DSS)

The S protein's stability can be reduced by increasing the coil, bending, and turning, and decreasing the β-sheets and α-helices. Figure 7 shows that all the analyzed perovskites decrease the S protein’s stability.

Figure 7. Distribution of secondary structures for S protein without and with BaTiO₃, CaTiO₃, and SrTiO₃ nanostructures. Image Credit: Khedri, M., et al., 2021.

Discussion

Based on the energy diagram it can be deduced that SrTiO₃ is better at reducing VdW and electrostatic energy levels when compared to the other nanostructures. SrTiO₃ also tops as the best nano-perovskite structure based on the radius of gyration.

RMSD and RMSF analysis show that using a perovskite can limit the flexibility of the structure, which is undesirable. SrTiO₃ is also the best for controlling the diffusion of S protein, along with reducing the number of hydrogen bonds more significantly than other nanostructures.

Conclusion

Examining the effects of various simulated nano-perovskite structures showed that nano-SrTiO₃ can effectively prevent COVID-19 by distorting and deforming the S protein, thereby decreasing the possibility of penetration and viral propagation.

Continue reading: Cicada's Antimicrobial Nanotechnology Solution for COVID-Free Surfaces.

Journal Reference:

Khedri, M., Zandi, P. Ghasemy E., Nikzad, A., Maleki, R., Rezaei, N., (2021) In-silico study on perovskites application in capturing and distorting coronavirus. Informatics in Medicine Unlocked, 26, p. 100755. Available at: https://doi.org/10.1016/j.imu.2021.100755.

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