Evidence for the Immune-Toxicity of Green Tea Polyphenols: A Computational Study

Adverse drug reactions (ADR) triggered by a drug or its metabolites is an essential aspect of the post-clinical phase in the drug discovery pipeline. The pathophysiology of ADRs has been described in two ways; expected and idiosyncratic. In the current study, we deployed valid computational tools to predict the ability of eight green tea polyphenols to favourably interact with HLA-B*57:01 and mediate idiosyncratic ADRs. First, we deployed molecular docking to understand the free energy profiles before and during peptide presentation scenarios. To better understand the significance of docking, we resolved the chemistry of interactions, similarity coefficients and pharmacophore parameter with which we used to filter four compounds that could be potentially ADR-liable. Our results and inferences were guided by a validation set which contained known HLA-B*57:01 ADR-mediators and a random set of non-ADR mediators. Overall, we show the potential of GTPs in activating T-cell receptors via HLA-B*57:01 which is a timely information for pharmaceutical companies that are testing these compounds in clinical trials.