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STM:治疗丙肝,过敏症药物显神通

新药编辑:新特药 更新时间:2015-04-12

2015年4月10日 讯 / --近日一项来自国立卫生研究院的研究结果表明,治疗过敏症状的药物盐酸氯环嗪(CCZ)或许可以抑制丙肝小鼠机体中丙型肝炎病毒的活性,相关研究刊登于国际杂志Science Translational Medicine,这种药物或许可以被用于进行丙肝患者的治疗。

丙肝病毒(HCV)可以引发机体肝脏炎症,经常会导致严重的并发症,比如肝硬化等;HCV的早期诊断和治疗可以有效抑制患者的肝脏损伤,目前有许多可治疗HCV感染的药物,但价格都比较昂贵。

研究者T. Jake Liang博士表示,尽管丙肝可以治愈,但目前急需要有效且患者可负担得起的药物,盐酸氯环嗪或许就是一种潜在的候选药物来减缓HCV患者的疾病症状。我们发现盐酸氯环嗪可以通过干扰病毒进入人类肝脏细胞的能力来阻断HCV的早期感染(人类的肝脏细胞移植入小鼠中进行研究),而且预后也同常见的抗病毒药物相类似,且没有任何药物副作用。

利用这种创新性的高通量筛选技术,研究者就发现盐酸氯环嗪或许是丙肝的潜在抑制药物,下一步研究者将研究该药物如何影响人类机体的HCV,盐酸氯环嗪当前用于治疗过敏症,后期当研究者阐明盐酸氯环嗪的安全性和有效性后,该药物或许就可以用于治疗丙肝患者的疾病了。

最后研究者Griffin P. Rodgers指出,盐酸氯环嗪疗法或许最终会为丙肝患者提供一种可负担得起的药物治疗模式,尤其是对那些丙肝感染非常普遍的高发资源缺乏区域将无疑是一大福利和帮助。

doi:10.1126/scitranslmed.3010286

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PMID:

Repurposing of the antihistamine chlorcyclizine and related compounds for treatment of hepatitis C virus infection

Shanshan He1, Billy Lin1, Virginia Chu1, Zongyi Hu1, Xin Hu2, Jingbo Xiao2, Amy Q. Wang2, Cameron J. Schweitzer1, Qisheng Li1, Michio Imamura3, Nobuhiko Hiraga3, Noel Southall2, Marc Ferrer2, Wei Zheng2, Kazuaki Chayama3, Juan J. Marugan2 and T. Jake Liang1,*

Hepatitis C virus (HCV) infection affects an estimated 185 million people worldwide, with chronic infection often leading to liver cirrhosis and hepatocellular carcinoma. Although HCV is curable, there is an unmet need for the development of effective and affordable treatment options. Through a cell-based high-throughput screen, we identified chlorcyclizine HCl (CCZ), an over-the-counter drug for allergy symptoms, as a potent inhibitor of HCV infection. CCZ inhibited HCV infection in human hepatoma cells and primary human hepatocytes. The mode of action of CCZ is mediated by inhibiting an early stage of HCV infection, probably targeting viral entry into host cells. The in vitro antiviral effect of CCZ was synergistic with other anti-HCV drugs, including ribavirin, interferon-α, telaprevir, boceprevir, sofosbuvir, daclatasvir, and cyclosporin A, without significant cytotoxicity, suggesting its potential in combination therapy of hepatitis C. In the mouse pharmacokinetic model, CCZ showed preferential liver distribution. In chimeric mice engrafted with primary human hepatocytes, CCZ significantly inhibited infection of HCV genotypes 1b and 2a, without evidence of emergence of drug resistance, during 4 and 6 weeks of treatment, respectively. With its established clinical safety profile as an allergy medication, affordability, and a simple chemical structure for optimization, CCZ represents a promising candidate for drug repurposing and further development as an effective and accessible agent for treatment of HCV infection.

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