On Aug 29，the journal of Science Bulletin published an article entitled “Cyclovirobuxine D inhibits dengue virus replication by impeding the complete autophagy via a cholesterol-dependent manner” from Prof. Jianfeng Dai’s Laboratory of Soochow University, which revealed the anti-Dengue virus activity of a novel compound, cyclovirobuxine D.
Dengue virus (DENV) is the most common mosquito-borne flavivirus, and it affects millions of people globally every year. Currently, there are no approved drugs for the treatment of dengue infection. By screening a natural product library, Dai Lab identified a novel compound, cyclovirobuxine D (Cvb D), that displays anti-DENV activity. Cvb D inhibits DENV replication in vitro in a dose-dependent manner and protects suckling mice against lethal DENV infection. Mechanistically, Cvb D regulates the expression of genes related to the cellular cholesterol pathway. As a result, Cvb D increases cellular cholesterol synthesis and accumulation, activates mTOR, and inhibits viral-dependent autophagy. Cvb D does not suppress autophagy initiation but impedes the nuclear translocation of the lysosome transcription factor TFEB. In addition, Cvb D restricts the replication of other positive-strand RNA viruses such as Zika virus and Coxsackievirus B3. We speculate that Cvb D could be a broad-spectrum antiviral drug candidate for use against positive-strand RNA viruses that require autophagy for optimal replication.
Kezhen Wang, Jinyu Zhang and Yunfei Ge are co-first authors of the paper. Prof. Jianfeng Dai is the corresponding author. Prof. Chunsheng Dong participated in this work. This work was supported National Natural Science Foundation of China (31770933, 81971917), Natural Science Foundation of Colleges in Jiangsu Province (17KJA310005) and Open Project Fund from State Key Laboratory of Genetic Engineering, Fudan University (SKLGE1903).