{"title":"Expanding horizons of iminosugars as broad-spectrum anti-virals: mechanism, efficacy and novel developments","authors":"Qiantong Liu, Yanyun Liu, Tingting Liu, Jinbao Fan, Zanxian Xia, Yingjun Zhou, Xu Deng","doi":"10.1007/s13659-024-00477-5","DOIUrl":null,"url":null,"abstract":"<div><p>Iminosugars, a class of polyhydroxylated cyclic alkaloids with intriguing properties, hold promising therapeutic potentials against a broad spectrum of enveloped viruses, including DENV, HCV, HIV, and influenza viruses. Mechanistically, iminosugars act as the competitive inhibitors of host endoplasmic reticular α-glucosidases I and II to disrupt the proper folding of viral nascent glycoproteins, which thereby exerts antiviral effects. Remarkably, the glycoproteins of many enveloped viruses are significantly more dependent on the calnexin pathway of the protein folding than most host glycoproteins. Therefore, extensive interests and efforts have been devoted to exploit iminosugars as broad-spectrum antiviral agents. This review provides the summary and insights into the recent advancements in the development of novel iminosugars as effective and selective antiviral agents against a variety of enveloped viruses, as well as the understandings of their antiviral mechanisms.</p><h3>Graphical Abstract</h3>\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":null,"pages":null},"PeriodicalIF":4.8000,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11427655/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Natural Products and Bioprospecting","FirstCategoryId":"92","ListUrlMain":"https://link.springer.com/article/10.1007/s13659-024-00477-5","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
Iminosugars, a class of polyhydroxylated cyclic alkaloids with intriguing properties, hold promising therapeutic potentials against a broad spectrum of enveloped viruses, including DENV, HCV, HIV, and influenza viruses. Mechanistically, iminosugars act as the competitive inhibitors of host endoplasmic reticular α-glucosidases I and II to disrupt the proper folding of viral nascent glycoproteins, which thereby exerts antiviral effects. Remarkably, the glycoproteins of many enveloped viruses are significantly more dependent on the calnexin pathway of the protein folding than most host glycoproteins. Therefore, extensive interests and efforts have been devoted to exploit iminosugars as broad-spectrum antiviral agents. This review provides the summary and insights into the recent advancements in the development of novel iminosugars as effective and selective antiviral agents against a variety of enveloped viruses, as well as the understandings of their antiviral mechanisms.
亚氨基糖苷是一类多羟基环状生物碱,具有引人入胜的特性,对包括 DENV、HCV、HIV 和流感病毒在内的多种包膜病毒具有良好的治疗潜力。从机理上讲,亚氨基糖苷是宿主内质网α-糖苷酶 I 和 II 的竞争性抑制剂,能破坏病毒新生糖蛋白的正常折叠,从而发挥抗病毒作用。值得注意的是,与大多数宿主糖蛋白相比,许多包膜病毒的糖蛋白更依赖于蛋白质折叠的钙粘蛋白途径。因此,人们对利用亚氨基糖作为广谱抗病毒剂投入了广泛的兴趣和努力。本综述总结并深入探讨了最近在开发新型亚氨基糖作为有效和选择性抗病毒药物以对抗多种包膜病毒方面取得的进展,以及对其抗病毒机制的理解。