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甲醇提取物抑制丙型肝炎病毒感染的早期病毒进入步骤。

Methanolic Extract of Inhibits the Early Viral Entry Steps of Hepatitis C Virus Infection.

机构信息

Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, 807 Kaohsiung, Taiwan.

Department of Clinical Pathology, Chi Mei Medical Center, Tainan 710, Taiwan.

出版信息

Viruses. 2018 Nov 27;10(12):669. doi: 10.3390/v10120669.

Abstract

Hepatitis C Virus (HCV) remains an important public health threat with approximately 170 million carriers worldwide who are at risk of developing hepatitis C-associated end-stage liver diseases. Despite improvement of HCV treatment using the novel direct-acting antivirals (DAAs) targeting viral replication, there is a lack of prophylactic measures for protection against HCV infection. Identifying novel antivirals such as those that target viral entry could help broaden the therapeutic arsenal against HCV. Herein, we investigated the anti-HCV activity of the methanolic extract from (RC), a widely used traditional Chinese medicine documented by the WHO and experimentally reported to possess several pharmacological functions including antiviral effects. Using the cell culture-derived HCV system, we demonstrated that RC dose-dependently inhibited HCV infection of Huh-7.5 cells at non-cytotoxic concentrations. In particular, RC blocked HCV attachment and entry/fusion into the host cells without exerting any significant effect on the cell-free viral particles or modulating key host cell entry factors to HCV. Moreover, RC robustly suppressed HCV pseudoparticles infection of Huh-7.5 cells and impeded infection by several HCV genotypes. Collectively, our results identified RC as a potent antagonist to HCV entry with potential pan-genotypic properties, which deserves further evaluation for use as an anti-HCV agent.

摘要

丙型肝炎病毒(HCV)仍然是一个重要的公共卫生威胁,全球约有 1.7 亿携带者面临发展为丙型肝炎相关终末期肝病的风险。尽管新型直接作用抗病毒药物(DAAs)靶向病毒复制改善了 HCV 的治疗,但缺乏针对 HCV 感染的预防措施。鉴定新型抗病毒药物,如针对病毒进入的药物,可能有助于扩大针对 HCV 的治疗武器库。在此,我们研究了(RC)的甲醇提取物的抗 HCV 活性,RC 是一种被世界卫生组织(WHO)广泛使用的传统中药,实验报告具有多种药理作用,包括抗病毒作用。使用细胞培养衍生的 HCV 系统,我们证明 RC 在非细胞毒性浓度下剂量依赖性地抑制 Huh-7.5 细胞中的 HCV 感染。特别是,RC 阻断 HCV 与宿主细胞的附着和进入/融合,而对无细胞病毒颗粒或调节 HCV 关键宿主细胞进入因子没有任何显著影响。此外,RC 强烈抑制 Huh-7.5 细胞中 HCV 假病毒的感染,并阻碍几种 HCV 基因型的感染。总之,我们的结果表明 RC 是一种有效的 HCV 进入拮抗剂,具有潜在的泛基因型特性,值得进一步评估作为抗 HCV 药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4969/6315547/af3a3d07f4fa/viruses-10-00669-g001.jpg

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