Repurposing an old drug: A low-cost allergy medication provides new hope for hepatitis C patients.
Repurposing an old drug: A low-cost allergy medication provides new hope for hepatitis C patients.
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DOI：
10.1002/hep.28028
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发表时间：
2015-12-01
期刊：
影响因子：
--
通讯作者：
Rice, Charles M
中科院分区：
文献类型：
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作者：
Chen, Zhilei;Rice, Charles M
丙型肝炎病毒（HCV）是丙型肝炎的病原体，影响约320万美国人和全世界超过1.85亿人。慢性丙型肝炎占肝细胞癌发病率的50%以上，肝细胞癌是美国癌症相关死亡增长最快的原因。在缺乏丙型肝炎保护性疫苗的情况下，仍然迫切需要有效和负担得起的治疗方案。最近有报道称，已有数十年历史的第一代抗组胺药氯环嗪在移植有原代人肝细胞的嵌合小鼠体内具有有效的抗HCV活性。1氯环嗪通过一种尚未确定的机制抑制晚期HCV进入。氯环嗪（商品名Ahist）是一种非处方的第一代苄基哌嗪类抗组胺药，用于治疗过敏相关症状，包括鼻塞、流鼻涕、瘙痒和打喷嚏。氯环嗪的抗病毒作用与现有的HCV治疗方法（包括利巴韦林、干扰素和病毒复制抑制剂）具有协同作用，增强了其作为联合抗HCV治疗方案成员的潜力。它已被使用了几十年，在患者中具有既定的安全性。Liang及其同事通过对3800个小分子进行基于细胞的高通量筛选，发现氯环嗪和相关分子具有抗HCV活性。
Hepatitis C virus (HCV), the causative agent of hepatitis C, affects about 3.2 million Americans and over 185 million people worldwide. Chronic hepatitis C accounts for> 50% of the incidence of hepatocellular carcinoma, the fastest-growing cause of cancer-related death in the United States. In the absence of a protective vaccine for hepatitis C, effective and affordable treatment options remain urgently needed. A decades-old first-generation antihistamine drug, chlorcyclizine, was recently reported to possess potent anti-HCV activity in vivo in chimeric mice engrafted with primary human hepatocytes. 1 Chlorcyclizine inhibits a late stage of HCV entry through a yet-to-be identified mechanism. The antiviral effect of chlorcyclizine is synergistic with existing HCV therapies, including ribavirin, interferona, and inhibitors of viral replication, bolstering its potential as a member of combination anti-HCV therapeutic regimens.Chlorcyclizine (trade name Ahist) is an over-thecounter first-generation antihistamine of the benzylpiperazine class used for treating allergy-related symptoms including stuffy nose, runny nose, itching, and sneezing. It has been used for decades with an established safety profile in patients. Liang and coworkers found that chlorcyclizine and related molecules possessed anti-HCV activity by conducting a cell-based highthroughput screen of 3800 small molecules in the