Targeting HSV-1 glycoprotein D through riboflavin-mediated photodynamic therapy: Insights from bioinformatics analysis and in vitro evaluation

Abstract

Introduction

The herpes simplex virus type 1 (HSV-1) causes painful viral lesions in the mucosal and cutaneous areas of the oral cavity as well as the head and neck. photodynamic therapy (PDT) effectively inactivates HSV-1 by targeting multiple structures and molecules without the risk of developing resistant strains. The most significant factor influencing the antiviral efficacy of PDT is the type of photosensitizer used. Therefore, finding more effective photosensitizers is essential. This study utilizes biological databases and bioinformatics tools to investigate computational simulations, molecular docking, and the in vitro antiviral effects of PDT using riboflavin in combination with a light-emitting diode (LED) against HSV-1.

Materials and Methods

The three-dimensional structures of glycoprotein D, the viral attachment protein of HSV-1, were predicted and validated using in silico methods. The physicochemical properties of this protein and the quality of the model were assessed. Molecular docking was performed, followed by the determination of the ADME/Tox profile, pharmacokinetic properties, and drug-likeness characteristics of riboflavin. Changes in viral load following PDT using riboflavin against HSV-1 were assessed by a virus titration assay and quantitative polymerase chain reaction (qPCR).

Results

It was determined that riboflavin does not violate Lipinski’s Rule of Five as a widely used guideline that predicts the likelihood of a compound being orally active in humans. Riboflavin was classified as toxicity class 6 (very low toxicity) and was found to be non-toxic to the liver, non-immunotoxic, and non-cytotoxic. Molecular docking studies using the three-dimensional model of glycoprotein D with the riboflavin ligand showed good binding affinity. Additionally, the in vitro results of the study showed that LED-activated riboflavin effectively inhibits HSV-1 replication during PDT, resulting in a significant reduction in viral load (P<0.05).

Conclusion

The study’s findings indicate that riboflavin, possessing drug-like characteristics, can successfully engage with glycoprotein D, demonstrating a high binding affinity. Additionally, PDT using riboflavin has been shown to effectively suppress HSV-1 replication. Consequently, riboflavin-mediated PDT, by lowering viral load, emerges as a promising supplementary treatment for HSV-1.