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

Juanbin Yin; Shasha Wang; Shanhui Ren; Zhengji Liang; Junwei Ge; Yuefeng Sun; Xiangping Yin; Xiangwei Wang

doi:10.3389/fmicb.2023.1284439

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

Front Microbiol. 2023 Dec 1:14:1284439. doi: 10.3389/fmicb.2023.1284439. eCollection 2023.

Authors

Juanbin Yin^#^{1

2}, Shasha Wang^#¹, Shanhui Ren¹, Zhengji Liang¹, Junwei Ge², Yuefeng Sun¹, Xiangping Yin¹, Xiangwei Wang¹

Affiliations

¹ State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
² Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, China.

^# Contributed equally.

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.

Keywords: TMP269; antiviral; autophagy; histone deacetylase inhibitor; rabies virus (RABV).

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was partially supported by the National Natural Science Foundation Project of China (grant no. 32202779).