Bisbenzylisoquinoline alkaloids inhibit influenza virus replication by disrupting endosomal acidification.

IF 4 3区 医学 Q2 VIROLOGY
Bo Li, Lijun Qiao, Xingqiong Li, Ge Yang, Kun Wang, Huiqiang Wang, Shuo Wu, Haiyan Yan, Jiandong Jiang, Yuhuan Li
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Abstract

Influenza virus, known for causing recurrent epidemics and pandemics, pose a significant public health challenge due to their rapid mutation rates and the emergence of drug resistance. This emphasizes the urgent need for the development of novel antiviral drugs. In this study, we identified five bisbenzylisoquinoline alkaloids (BBAs)-cepharanthine (CEP), tetrandrine (TET), fangchinoline (FCN), berbamine (BBM) and iso-tetrandrine (Iso-TET)-that exhibit antiviral activity against influenza virus, as determined through cytopathic effect inhibition screening. These compounds showed dose-dependent suppression of viral replication by targeting the early stages of the viral life cycle, specifically through disruption of endosomal acidification and inhibition of viral genome release into the cytoplasm. Notably, treatment with the representative compound CEP significantly reduced viral load in the lungs and improved lung pathology in infected models. These findings highlight the potential of BBAs, particularly CEP, as promising candidates for the development of therapeutics against influenza virus infections.

双苄基异喹啉生物碱通过破坏内体酸化抑制流感病毒复制。
流感病毒以引起反复流行和大流行而闻名,由于其快速突变率和耐药性的出现,对公共卫生构成重大挑战。这强调了开发新型抗病毒药物的迫切需要。在这项研究中,我们鉴定了五种双苄基异喹啉类生物碱(BBAs)——头蒽素(CEP)、粉防己碱(TET)、防己碱(FCN)、小檗碱(BBM)和异粉防己碱(Iso-TET)——通过细胞病变效应抑制筛选确定了它们对流感病毒具有抗病毒活性。这些化合物通过靶向病毒生命周期的早期阶段,特别是通过破坏内体酸化和抑制病毒基因组释放到细胞质中,显示出剂量依赖性的病毒复制抑制。值得注意的是,用代表性化合物CEP治疗可显著降低肺部病毒载量,改善感染模型的肺部病理。这些发现突出了BBAs的潜力,特别是CEP,作为开发抗流感病毒感染治疗药物的有希望的候选者。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Virology Journal
Virology Journal 医学-病毒学
CiteScore
7.40
自引率
2.10%
发文量
186
审稿时长
1 months
期刊介绍: Virology Journal is an open access, peer reviewed journal that considers articles on all aspects of virology, including research on the viruses of animals, plants and microbes. The journal welcomes basic research as well as pre-clinical and clinical studies of novel diagnostic tools, vaccines and anti-viral therapies. The Editorial policy of Virology Journal is to publish all research which is assessed by peer reviewers to be a coherent and sound addition to the scientific literature, and puts less emphasis on interest levels or perceived impact.
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