アレルギーの薬がC型肝炎ウイルスの感染を阻止する可能性 米国NIHと茶山教授らの共同研究で判明



アレルギー症状の緩和に使われている安価な一般薬がC型肝炎ウイルスの感染阻止に有効かもしれないことを、米国立衛生研究所(NIH)と広島大学大学院医歯薬保健学研究院 茶山一彰教授の共同研究チームがキメラマウスを用いた実験で突き止め、4月8日発行のサイエンス・トランスレーショナル・メディシン誌に発表しました。薬剤耐性も引き起こさず、インビトロ試験では他のC型肝炎治療薬との同時投与によって効果が増すことも確認されました。

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



<Abstract>


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.



(Copyright(c) 2015, American Association for the Advancement of Science.)

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