Dengue virus (DENV) is one of the most prevalent arthropod-borne diseases. It may cause
dengue hemorrhagic fever (DHF) and
dengue shock syndrome (DSS), while no effective
vaccines and drugs are available. Our study demonstrated that
conessine exhibits broad
antiviral activity against several enveloped viruses, including DENV,
vesicular stomatitis virus, and herpes simplex virus. In addition,
conessine has no direct destructive effect on the integrity or infectivity of virions. Both pre-treatment and post-treatment with
conessine significantly reduce DENV replication. Pre-treatment with
conessine disrupts the endocytosis of enveloped viruses, while post-treatment disturbs DENV RNA replication or translation at an early stage. Through screening differentially expressed genes by transcriptome sequencing, we found that
conessine may affect
cholesterol biosynthesis, metabolism or homeostasis. Finally, we confirmed that
conessine inhibits virus replication through up-regulating
cholesterol levels. Our work suggests that
conessine could be developed as a prophylactic and therapeutic treatment for
infectious diseases caused by enveloped viruses.