Artesunate, an anti-malarial drug, has a potential to inhibit HCV replication

Artesunate, an anti-malarial drug, has a potential to inhibit HCV replication
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青蒿琥酯是一种抗疟疾药物,具有抑制丙肝病毒复制的潜力

DOI:
10.1007/s11262-015-1285-7
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发表时间:
2016-02-01
期刊:
影响因子:
1.6
通讯作者:
Gong, Guozhong
Gong, Guozhong
中科院分区:
医学4区
文献类型:
--
作者:
Dai, Rongjuan;Xiao, Xinqiang;Gong, Guozhong

文献摘要

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丙型肝炎病毒(HCV)感染是一个重大的全球健康问题。虽然丙型肝炎的治疗研究取得了很大的成果,但目前的治疗方法存在局限性,仍需要新的治疗方法和药物来治疗丙型肝炎。本研究的目的是研究青蒿琥酯(ART)对丙型肝炎病毒复制的影响,并与利巴韦林(RBV)和干扰素-2b(干扰素-2b)进行比较。这项研究是在丙型肝炎病毒感染细胞模型(JFH1感染Huh7.5.1和OR6细胞株)中进行的。我们的结果表明,抗疟药物ART以剂量和时间依赖的方式抑制丙型肝炎病毒复制子的复制,对指数生长的宿主细胞的增殖没有影响,qPCR、荧光素酶分析和Western印迹分析表明,ART对丙型肝炎病毒复制的抑制作用强于RBV,但弱于干扰素。此外,联合应用ART和干扰素可更有效地抑制丙型肝炎病毒的复制。这些发现表明,ART具有抑制丙型肝炎病毒复制的作用,可能是一种新的与干扰素和RBV联合治疗丙型肝炎病毒的方法,也可以作为一种替代策略来对抗在DAA试剂存在时出现的耐药性机制。
Hepatitis C virus (HCV) infection is a major global health issue. Although the search for HCV treatments has resulted in great achievements, the current treatment methods have limitations, and new methods and drugs for hepatitis C treatment are still required. The aim of the present study was to investigate the effects of artesunate (ART) on HCV replication and compared these effects with those of ribavirin (RBV) and interferon-2b (IFN). The study was performed in HCV-infection cell models (JFH1-infected Huh7.5.1 and OR6 cell lines). Our results showed that the antimalarial drug ART inhibited HCV replicon replication in a dose- and time-dependent manner at a concentration that had no effect on the proliferation of exponentially growing host cells, and the inhibitory effect on HCV replication was stronger than RBV but weaker than IFN, as determined by qPCR, luciferase assays, and Western blot analysis. Furthermore, the combination of ART and IFN resulted in a greater inhibition of HCV replication. These findings demonstrated that ART had an inhibitive effect on HCV replication and may be a novel supplemental co-therapy with IFN and RBV for HCV and as an alternative strategy to combat resistance mechanisms that have emerged in the presence of DAA agents.