Table_4_TMP269, a small molecule inhibitor of class IIa HDAC, suppresses RABV replication in vitro.XLS

TMP269, a small molecular inhibitor of IIa histone deacetylase, plays a vital role in cancer therapeutic. However, the effect of TMP269 on the regulation of viral replication has not been studied. In the present study, we found that TMP269 treatment significantly inhibited RABV replication at concentrations without significant cytotoxicity in a dose-dependent manner. In addition, TMP269 can reduce the viral titers and protein levels of RABV at an early stage in the viral life cycle. RNA sequencing data revealed that immune-related pathways and autophagy-related genes were significantly downregulated after RABV infection treated with TMP269. Further exploration shows that autophagy enhances RABV replication in HEK-293T cells, while TMP269 can inhibit autophagy to decrease RABV replication. Together, these results provide a novel treatment strategy for rabies.

TMP269是一种IIa类组蛋白去乙酰化酶（IIa histone deacetylase）小分子抑制剂，在癌症治疗中发挥关键作用。然而，目前尚未有研究探讨TMP269对病毒复制的调控作用。本研究发现，在无显著细胞毒性的浓度范围内，TMP269可呈剂量依赖性地显著抑制狂犬病病毒（RABV）的复制。此外，在病毒生命周期的早期阶段，TMP269可降低RABV的病毒滴度及蛋白表达水平。RNA测序（RNA sequencing）数据显示，经TMP269处理的RABV感染细胞中，免疫相关通路及自噬相关基因的表达显著下调。进一步研究表明，自噬可促进HEK-293T细胞内的RABV复制，而TMP269可通过抑制自噬从而降低RABV的复制水平。综上，本研究结果为狂犬病的治疗提供了全新的策略。