Key Laboratory of Biotechnology of Antibiotics, the National Health Commission (NHC), Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
J Nat Prod. 2022 Apr 22;85(4):1018-1028. doi: 10.1021/acs.jnatprod.1c01161. Epub 2022 Feb 24.
Isarubrolone C is a bioactive polycyclic tropoloalkaloid from . Our previous study showed that isarubrolone C could trigger autophagy. Here, we report isarubrolone C potential in broad-spectrum antiviral effect and its antiviral mechanism . Our results show that isarubrolone C activated autophagy and reduced levels of viral proteins in the cells harboring HCV-CORE/NS5B, HBx, ZIKV-NS5, and HIV-RT, respectively. The role of isarubrolone C in suppression of the viral proteins was via an autophagic degradation pathway rather than a proteasome pathway. Co-immunoprecipitation assays revealed that isarubrolone C promoted both autophagy flux opening and the viral proteins being enwrapped in autolysosomes. PCR assays showed that isarubrolone C elevated the transcription levels of / and . Further, ATG10S high expression could efficiently enhance IL28A expression and the ability of isarubrolone C to degrade the viral proteins by promoting the colocalization of viral proteins with autolysosomes. Additionally, knockdown of endogenous caused both losses of the isarubrolone C antiviral effect and autolysosome formation. These results indicate that the role of isarubrolone C antiviruses is achieved by triggering the autophagic mechanism, which is mediated by endogenous ATG10S and IL28A activation. This is the first report about isarubrolone C potential of broad-spectrum antiviruses.
异长春花碱 C 是一种来源于 的生物活性多环色胺生物碱。我们之前的研究表明，异长春花碱 C 可以触发自噬。在这里，我们报告了异长春花碱 C 在广谱抗病毒作用及其抗病毒机制方面的潜力。我们的结果表明，异长春花碱 C 激活了自噬，并降低了分别含有 HCV-CORE/NS5B、HBx、ZIKV-NS5 和 HIV-RT 的细胞中病毒蛋白的水平。异长春花碱 C 抑制病毒蛋白的作用是通过自噬降解途径而不是蛋白酶体途径。免疫共沉淀实验表明，异长春花碱 C 促进了自噬流的开放和病毒蛋白被包裹在自噬溶酶体中。PCR 实验表明，异长春花碱 C 升高了 / 和 的转录水平。此外，ATG10S 的高表达可以通过促进病毒蛋白与自噬溶酶体的共定位，有效地增强 IL28A 的表达和异长春花碱 C 降解病毒蛋白的能力。此外，内源性 的敲低导致异长春花碱 C 的抗病毒作用和自噬溶酶体形成的丧失。这些结果表明，异长春花碱 C 抗病毒作用的发挥是通过触发自噬机制实现的，该机制由内源性 ATG10S 和 IL28A 的激活介导。这是关于异长春花碱 C 广谱抗病毒潜力的首次报道。
