EGCG debilitates the persistence of EBV latency by reducing the DNA binding potency of nuclear antigen 1

► Two cell-based reporter platforms were established for screening of EBNA1 inhibitors. ► EGCG acts as an inhibitor to block EBNA1 binding with the cognate oriP sequence. ► EGCG debilitates EBNA1-dependent transcription enhancement and episome maintenance. ► EGCG impairs persistence of EBV latency. ► EGCG is a potent anti-EBV agent for targeting the latent cascade of EBV.