Conessine inhibits enveloped viruses replication through up-regulating cholesterol level.

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.