Virtual Screening to Identify the Protein Network Interaction of Theophylline in Red Complex Pathogens

Abstract

Background: Plants, herbs and plant derived compounds have been used since decades in folk and traditional medicine. These compounds were found to be non-toxic and compatible with the human cells. Screening of this exhaustive collection of compounds seems to be a herculean task. Hence, virtual screening methods have been developed to predict the potential targets of these compounds enabling researchers to acquire preliminary data on the compound intended to be tested in vitro. Aim: The present study aims to identify protein targets of theophylline in red complex pathogens which are mainly associated with periodontitis. Methods: The STITCH v5.0 pipeline was mainly used to classify drug-protein interactions, while VirulentPred and VICMPred were used to determine the proteins' virulence properties and functional classes. PSORTb v3.0 was used to determine the subcellular localization of viral proteins, and BepiPred v1.0 Linear Epitope Prediction was used to classify epitopes. Results: Proteins of red complex pathogens implicated in cellular process, metabolism, and virulence were identified to interact with theophylline. The virulent proteins attacked by the drugs were present in the cytoplasm, which would improve the drugs' antimicrobial efficacy even more. Finally, epitope prediction showed a number of epitopes in virulent proteins that can be targeted. Conclusions: Proteins involved in the cellular process, metabolism, and virulence of red complex pathogens targeted by theophylline were identified. To substantiate the true interactions between the drugs and the protein arsenal of pathogens, further in vitro experiments on a broad range of pathogens are required.