Medical Research Center, Guangdong Second Provincial General Hospital, Jinan University, Guangzhou, Guangdong Province, 510317, China.
Medical Research Center, Guangdong Second Provincial General Hospital, Jinan University, Guangzhou, Guangdong Province, 510317, China.
Virus Res. 2023 Dec;338:199234. doi: 10.1016/j.virusres.2023.199234. Epub 2023 Oct 16.
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.
登革热病毒（DENV）是最常见的虫媒病毒之一。它可能引起登革出血热（DHF）和登革休克综合征（DSS），但目前尚无有效的疫苗和药物。我们的研究表明，可可尼定对几种包膜病毒具有广泛的抗病毒活性，包括登革热病毒、水疱性口炎病毒和单纯疱疹病毒。此外，可可尼定对病毒粒子的完整性或感染力没有直接的破坏作用。可可尼定的预处理和后处理均可显著降低 DENV 的复制。预处理可可尼定会破坏包膜病毒的内吞作用，而后处理则会在早期干扰 DENV RNA 的复制或翻译。通过转录组测序筛选差异表达基因，我们发现可可尼定可能影响胆固醇的生物合成、代谢或平衡。最后，我们证实可可尼定通过上调胆固醇水平来抑制病毒复制。我们的工作表明，可可尼定可被开发为预防和治疗包膜病毒引起的传染病的药物。
