Machine learning-driven prediction of EBNA1 inhibitors against Epstein–Barr virus in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC), particularly prevalent in regions such as Malaysia, is a significant health concern often linked to Epstein-Barr virus (EBV) infection. The EBV nuclear antigen 1 (EBNA1), crucial for EBV survival and NPC tumorigenicity, has emerged as a potential therapeutic target for EBV-positive NPC. In this study, we utilized quantitative structure-activity relationship (QSAR) models to predict potential inhibitors of EBNA1. These models were developed based on the molecular fingerprints of known EBNA1 inhibitors, using both classification and regression approaches. Our QSAR classification models demonstrated consistently high precision, recall, F1 score, and accuracy scores across the training set. The top-performing models, constructed using logistic regression algorithms, achieved perfect precision scores of 1.000 in the test set evaluation. These models’ recall, F1 score, and accuracy scores were 0.571, 0.727, and 0.667, respectively. On the other hand, the best-performing model among the regression models was built using the sequential minimal optimization regression algorithm, achieving a correlation coefficient of 0.703. The mean absolute error and root mean square error of this QSAR regression model were 0.173 and 0.217, respectively, whereas the relative absolute error was 0.689. We screened the enamine advanced compound library using this regression model to predict compounds with potential EBNA1 inhibitory effects. This led to the identification of the top 10 compounds with the most promising predicted EBNA1 inhibitory properties.