Molecular Modeling and Simulation Analysis of Antimicrobial Photodynamic Therapy Potential for Control of COVID-19

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can enter the host cells by binding the viral surface spike glycoprotein (SG) to angiotensin-converting enzyme 2. Since antiviral photodynamic therapy (aPDT) has been described as a new method for inhibiting viral infections, it is important to evaluate whether it can be used as a photoactivated disinfectant to control COVID-19. In this in silico study, SARS-CoV-2-SG was selected as a novel target for curcumin as a photosensitizer during aPDT to exploit its physicochemical properties, molecular modeling, hierarchical nature of protein structure, and functional analysis using several bioinformatics tools and biological databases. The results of a detailed computational investigation revealed that SARS-CoV-2-SG is most similar to 6VXX_A, with 100% query cover and identity. The predicted structure of SARS-CoV-2-SG displayed that it is a protein with a positive charge and random coil dominates other secondary structures located outside the viral cell. The protein-protein interaction network showed that SARS-CoV-2-SG interacted with ten potential interacting partners. In addition, primary screening of binding modes through molecular docking showed that curcumin desires to bind and interact with residues of SARS-CoV-2-SG as the main site to enhance the yield of aPDT. Overall, the computer simulation reveals that SARS-CoV-2-SG can be a suitable target site for interaction with curcumin during aPDT.

Figure 1

Secondary structure prediction of SARS-CoV-2-SG using (a) PSIPRED and (b) GOR IV.

Figure 2

Bioinformatics analysis and computer simulation molecular modeling of SARS-CoV-2-SG. (a) Three-dimensional structures, (b) QMEAN value, (c) local model quality overall model quality, and (d) comparison with a nonredundant set of SARS-CoV-2-SG structure.

Figure 3

Ramachandran plot of SARS-CoV-2-SG by PROCHECK server.

Figure 4

Evaluation of protein model of SARS-CoV-2-SG by ERRAT.

Figure 5

Evaluation of protein model of SARS-CoV-2-SG by SAVES.

Figure 6

Evaluation of protein model of SARS-CoV-2-SG by VERIFY3D.

Figure 7

ProSA output for SARS-CoV-2-SG. (a) Overall model quality with ProsaWeb server and (b) local model quality with ProsaWeb server.

Figure 8

Protein-protein interaction map of SARS-CoV-2-SG by STRING.

Figure 9

Identification of signal peptide in SARS-CoV-2-SG by PROTTER.

Figure 10

Result of motif finder in SARS-CoV-2-SG.

Figure 11

Docking analysis between ligands of the modeled SARS-CoV-2-SG doped with curcumin.