抗日本乙型脑炎病毒的线粒体靶向小分子化合物的筛选及鉴定OA北大核心CSTPCD

[Objectives]Mitochondria,an important energy metabolism organelle,can not only affect virus replication by regulating host innate immunity,but also its biological function changes are significant involved in virus life cycle.This study aimed to search for mitochondrial targeting compounds that inhibited Japanese encephalitis virus(JEV).[Methods]In this study,382 mitochondrial targeting compounds were indentified in vitro through experiments such as CCK-8,indirect immunofluorescence,Western blot,RT-qPCR and cytokine detection tests,and the screening results were further validated in mice.[Results]Through preliminary screening of drugs,9 suspected anti-JEV drugs were selected from 382 drugs.Further in vitro molecular screening determined that 3 of these drugs had significant inhibitory effects on JEV replication,namely sodium 2-oxopropanoate,brequinar and echinacoside.The results of mouse animal experiments showed that the three drugs effectively inhibited the proliferation of JEV in mice,and the body weight of the treated mice increased significantly compared to the control group.The virus content in the blood was lower,the mortality rate was lower,and the cytokine levels showed significant changes,with the most significant change in the buquinavir-treated group.[Conclusions]This study successfully screened three anti JEV mitochondrial targeting compounds,providing new idea for exploring the impact of mitochondria on viral replication,and also for clinical drug research on anti-JEV.