1. TMP269, a small molecule inhibitor of class IIa HDAC, suppresses RABV replication in vitro.
- Author
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Juanbin Yin, Shasha Wang, Shanhui Ren, Zhengji Liang, Junwei Ge, Yuefeng Sun, Xiangping Yin, and Xiangwei Wang
- Subjects
SMALL molecules ,LIFE cycles (Biology) ,HISTONE deacetylase inhibitors ,RNA sequencing ,CYTOTOXINS - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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