Molecular Docking Study of Potential Antimicrobial Photodynamic Therapy as a Potent Inhibitor of SARS-CoV-2 Main Protease: An In silico Insight

Abstract

Background: Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is rapidly spreading. Recently, antimicrobial photodynamic therapy (aPDT) using safe and cost-effective photosensitizers has been introduced as a valuable therapy for the eradication of microbial infections. Objective: This in silico study aimed to investigate the potential of aPDT against SARS-CoV-2 main protease (MPro). Methods: In this study, to evaluate possible inhibitors of SARS-CoV-2 during aPDT, a computational model of the SARS-CoV-2 MPro was constructed in complex with emodin, resveratrol, pterin, and hypericin as the natural photosensitizers. Results: According to the molecular docking analysis of protein-ligand complexes, emodin and resveratrol with a high affinity for SARS-CoV-2 MPro showed binding affinity -7.65 and -6.81 kcal/mol, respectively. All natural photosensitizers with ligand efficiency less than 0.3 fulfilled all the criteria of Lipinski’s, Veber’s, and Pfizer’s rules, except hypericin. Also, the results of molecular dynamic simulation confirmed the stability of the SARS-CoV-2 MPro and inhibitor complexes. Conclusion: As the results showed, emodin, resveratrol, and pterin could efficiently interact with the MPro of SARS CoV-2. It can be concluded that aPDT using these natural photosensitizers may be considered a potential SARS-CoV-2 MPro inhibitor to control COVID-19.