蝎毒素多肽探针Sm286在宿主抗病毒蛋白钾通道Kv1.3发现中的作用与机制研究

Animal toxin polypeptides are effective molecular probes for studying the structure and function of membrane ion channels. Viral infections cause great harm to human health, because there is no effective vaccine and specific clinical drugs against viral infection. Recently, we found that the scorpion toxin polypeptide Sm286 not only promotes hepatitis C virus (HCV) and dengue virus (DENV) replication in vitro, but also regulates the activity of Kv1.3 potassium channel on viral host cell membrane. Used “role and mechanism of host cell Kv1.3 during viral replication revealed by the molecular probe of scorpion toxin peptide Sm286” as the most scientific question, this project focuses on the following four aspects: 1) Effect of scorpion toxin peptide Sm286 on the replication of HCV, DENV and Zika virus (ZIKV); 2) Selective regulation of scorpion toxin polypeptide Sm286 on sodium/potassium plasma channel subtypes and its relationship with viral replication; 3) Role and mechanism of potassium channel Kv1.3 in the replication of HCV, DENV and ZIKV; 4) Molecular mechanism of scorpion toxin polypeptide Sm286 on virus replication mediated by Kv1.3 channel. These works will finally elucidates the antiviral effect and mechanism of potassium channel Kv1.3 from host cells, find potassium channel Kv1.3 as potential new antiviral drug target, and highlight the significant contribution that scorpion toxin peptide Sm286 was used as molecular probe in the study of the relationship between host cell ion channel and virus replication. These efforts lay a scientific foundation for innovating new strategies and new ways of using the special scorpion toxin polypeptide resources in our country and opening up new virus prevention and treatment.

动物毒素多肽是研究膜离子通道结构与功能的分子探针。病毒感染严重危害人类健康，临床上很多病毒仍无有效疫苗和特异性治疗药物。前期发现蝎毒素多肽Sm286不仅体外促进丙型肝炎和登革热病毒复制，而且调节病毒感染宿主细胞膜钾通道Kv1.3活性，本项目围绕Sm286作为分子探针揭示宿主细胞钾通道Kv1.3在病毒复制中作用机制关键科学问题，拟开展：Sm286对丙型肝炎、登革热和寨卡病毒复制的影响；Sm286对钾、钠等离子通道的选择性调节作用及其与影响病毒复制的关系；钾通道Kv1.3在丙型肝炎、登革热和寨卡病毒复制过程中的作用与机制；钾通道Kv1.3介导Sm286影响病毒复制的分子机制，最终阐明宿主细胞钾通道Kv1.3抗病毒作用与机制，发现抗病毒药物潜在新靶标钾通道，诠释蝎毒素多肽作为分子探针在宿主细胞离子通道与病毒复制之间关系研究中的贡献，创新利用我国特有蝎毒素多肽资源，开辟病毒病防治新策略与新途径。

动物毒素多肽是研究膜离子通道结构与功能的分子探针。病毒感染严重危害人类健康，临床上很多病毒仍无有效疫苗和特异性治疗药物。前期发现蝎毒素多肽Sm286不仅体外促进丙型肝炎和登革热病毒复制，而且调节病毒感染宿主细胞膜钾通道Kv1.3活性，本项目围绕Sm286作为分子探针揭示宿主细胞钾通道Kv1.3在病毒复制中作用机制关键科学问题，拟开展：Sm286对丙型肝炎、登革热和寨卡病毒复制的影响；Sm286对钾、钠等离子通道的选择性调节作用及其与影响病毒复制的关系；钾通道Kv1.3在丙型肝炎、登革热和寨卡病毒复制过程中的作用与机制；钾通道Kv1.3介导Sm286影响病毒复制的分子机制，最终阐明宿主细胞钾通道Kv1.3抗病毒作用与机制，发现抗病毒药物潜在新靶标钾通道，诠释蝎毒素多肽作为分子探针在宿主细胞离子通道与病毒复制之间关系研究中的贡献，创新利用我国特有蝎毒素多肽资源，开辟病毒病防治新策略与新途径。项目经过4年的运行，项目负责人以主要通讯作者在FASEB J (IF=5.834)、J Biol Chem. (IF=5.486)、Theranostics (IF=11.600)、Antiviral Res. (IF=10.103)、Int J Biol Sci. (IF=10.750)、Antibiotics (Basel) (IF=5.222)等杂志上发表SCI论文7篇。2021年参与编写了科学出版社出版的《生物毒素学》专著。已毕业博士研究生4名。项目组完成了原计划研究内容和达到了预期的研究目标，取得了系列研究成果。课题组以自然基金项目为契机，已经形成一个有特色的动物毒素多肽研究方向。