近日一項來自國立衛生研究院的研究結果表明，治療過敏症狀的藥物鹽酸氯環嗪(CCZ)或許可以抑製丙肝小鼠機體中丙型肝炎病毒的活性，相關研究刊登於國際雜誌Science Translational Medicine，這種藥物或許可以被用於進行丙肝患者的治療。
丙肝病毒（HCV）可以引發機體肝髒炎症，經常會導致嚴重的並發症，比如肝硬化等；HCV的早期診斷和治療可以有效抑製患者的肝髒損傷，目前有許多可治療HCV感染的藥物，但價格都比較昂貴。
研究者T. Jake Liang博士表示，盡管丙肝可以治愈，但目前急需要有效且患者可負擔得起的藥物，鹽酸氯環嗪或許就是一種潛在的候選藥物來減緩HCV患者的疾病症狀。我們發現鹽酸氯環嗪可以通過幹擾病毒進入人類肝髒細胞的能力來阻斷HCV的早期感染（人類的肝髒細胞移植入小鼠中進行研究），而且預後也同常見的抗病毒藥物相類似，且沒有任何藥物副作用。
利用這種創新性的高通量篩選技術，研究者就發現鹽酸氯環嗪或許是丙肝的潛在抑製藥物，下一步研究者將研究該藥物如何影響人類機體的HCV，鹽酸氯環嗪當前用於治療過敏症，後期當研究者闡明鹽酸氯環嗪的安全性和有效性後，該藥物或許就可以用於治療丙肝患者的疾病了。
最後研究者Griffin P. Rodgers指出，鹽酸氯環嗪療法或許最終會為丙肝患者提供一種可負擔得起的藥物治療模式，尤其是對那些丙肝感染非常普遍的高發資源缺乏區域將無疑是一大福利和幫助。
doi:10.1126/scitranslmed.3010286
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Repurposing of the antihistamine chlorcyclizine and related compounds for treatment of hepatitis C virusinfection
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.
