TMP269, a small molecule inhibitor of class IIa HDAC, suppresses RABV replication in vitro

TMP269, a small-molecule inhibitor of class IIa histone deacetylases, is known for its role in cancer therapy. However, its impact on viral replication remains unexplored. In this study, we found that TMP269 significantly inhibited rabies virus (RABV) replication in a dose-dependent manner at non-cytotoxic concentrations. Additionally, TMP269 reduced viral titers and protein levels during the early stages of the viral life cycle.

RNA sequencing analysis revealed that TMP269 treatment led to the downregulation of immune-related pathways and autophagy-related genes in RABV-infected cells. Further investigation demonstrated that autophagy promotes RABV replication in HEK-293T cells, while TMP269 suppresses autophagy, thereby reducing viral replication. These findings suggest that TMP269 offers a potential novel therapeutic strategy for rabies.