A small molecule that selectively inhibits the growth of Epstein-Barr virus-latently infected cancer cells

Summary: Epstein-Barr virus (EBV), an oncogenic herpesvirus, is predominantly found in the latent infection form and is highly associated with many human malignancies, which mainly have poor prognoses and no effective treatments. Here, we obtained thirteen compounds from small-molecule libraries for specific inhibition of EBV-latently infected cell growth in vitro by high-throughput screening. Among them, cetrimonium bromide (CetB) was identified to selectively inhibit the growth of different EBV-infected B lymphoma cell lines. Importantly, CetB reduced EBNA1 protein stability, activated G1 arrest and early apoptosis of EBV-latently infected cells without viral lytic reactivation, which leads to dramatically inhibit colony formation and tumor growth of EBV-infected cells in vitro and in vivo, and significantly prolong the survival of tumor-bearing mice. Overall, these findings demonstrate that CetB acts as a highly selective inhibitor of the growth of EBV-infected cells and has the potential for further development of effective therapeutic strategies specific against EBV-associated cancers.