抗丙肝病毒药物研发的最新进展(英文)  

Recent advance in antiviral drugs for hepatitis C

作　　者：刘佳[1] 石爽[1] 庄辉[1] 罗光湘[1,2] 

机构地区：[1]北京大学医学部病原生物学系,北京100191 [2]肯塔基大学医学院微生物、免疫与分子遗传学系,美国肯塔基州列克星顿40536

出　　处：《中南大学学报（医学版）》2011年第11期1025-1036,共12页Journal of Central South University ：Medical Science

摘　　要：丙型肝炎病毒(HCV)是引起慢性肝脏疾病的主要病因。目前尚无疫苗预防HCV感染。长效聚乙二醇I型干扰素(pegIFN-α)和利巴韦林(RBV)联合应用是近十年来治疗丙肝的最佳药物,但仍有一半以上基因1型HCV感染者对该联合抗病毒治疗无效,并且IFN和RBV的毒副作用较大且疗程长达1年,因此极大地限制了其在临床上的应用。近些年来,各制药公司相继研发出了多种HCV特异性的抗病毒药物,有些已经进入三期临床试验。今年美国食品药品管理局(FDA)批准了2种HCV蛋白酶抑制剂用于临床治疗丙肝,其他蛋白酶抑制剂、NS5A抑制剂及RNA聚合酶抑制剂也均处于三期临床试验阶段。因此,有望在不久的将来研发出不依赖于IFN、高效、安全、疗程短及服用次数少的理想治疗方案。Hepatitis C virus（HCV） infection is the leading cause of chronic liver diseases worldwide.There is no vaccine to prevent HCV infection.Current standard of care（SOC） for hepatitis C is pegylated interferon-α（pegIFN-α） in combination with ribavirin（RBV）.However,the efficacy of pegIFN-α and RBV combination therapy is less than 50% for genotype 1 HCV,which is the dominant virus in human.Additionally,IFN and RBV are highly toxic,causing severe side effects.Therefore,it is urgent to develop safer and more efficacious anti-HCV drugs.Over the last decade,a number of HCV-specific inhibitors have been discovered with many of them reached to late stages of clinical trials.Recently,2 HCV NS3 protease inhibitors,telaprevir and boceprevir,have been approved by the Unite States Food and Drug Administration（FDA）.This opens up a new era for anti-HCV therapy.Several new classes of antiviral drugs targeting HCV NS3 protease,NS5A and NS5B RNA-dependence RNA polymerase（RdRp） are currently at various stages of preclinical and clinical studies.Upon approval of more NS3 protease,NS5A and NS5B polymerase inhibitors,future clinical studies will lead to optimal combination therapies which will have desirable parameters such as IFN-free,higher efficacy,safe,one daily dose and short duration.

关 键 词：丙型肝炎病毒 抗病毒药物 NS3蛋白酶抑制剂 NS5A抑制剂 NS5B聚合酶抑制剂 联合治疗 

分 类 号：R512.63[医药卫生—内科学]