Insight into potent TLR2 inhibitors for the treatment of disease caused by Mycoplasma pneumoniae based on machine learning approaches.

Mycoplasma pneumoniae (MP) is one of the most common pathogens that causes acute respiratory tract infections. Children experiencing MP infection often suffer severe complications, lung injury, and even death. Previous studies have demonstrated that Toll-like receptor 2 (TLR2) is a potential therapeutic target for treating the MP-induced inflammatory response. However, the screening of natural compounds has received more attention for the treatment of bacterial infections to reduce the likelihood of bacterial resistance. Herein, we screened compounds by combining molecular docking and machine learning approaches to find potential lead compounds for treating MP infection. First, all compounds were docked with the TLR2 receptor protein to screen for potential candidates. To predict drug bioactivity, a machine learning model (random forest) was trained for TLR2 inhibitors to obtain the predictive model. The model achieved significant squared correlation coefficient (R2) values for the training set (0.85) and validation set (0.84) of compounds. The developed machine learning model was then used to predict the pIC50 values of the top 50 candidates from the Traditional Chinese compounds and Discovery Diversity sets of compounds. As a result, these compounds are capable of inhibiting the inflammatory response induced by MP. However, prior to bringing these compounds to market, it is necessary to verify these results with additional biological testing, including preclinical and clinical studies. Moreover, the present study provides a theoretical basis for the use of natural compounds as potential candidates to treat pneumonia caused by MP.