CAJ | 학술논문

慢性丙型肝炎病毒(HCV)感染是全球性的公共卫生问题之一,可导致严重的肝病,包括肝硬化及肝癌. 传统的标准治疗方案利巴韦林+聚乙二醇化干扰素对病毒响应率低,副作用大,难以有效治疗HCV感染. 近年来,多种新类型HCV抑制剂得以开发,包括直接抗病毒药物(DAA)以及宿主靶向药物. 这些药物针对病毒生命周期中的必需蛋白,主要包括NS3/4A蛋白酶、NS5B聚合酶、NS5A蛋白或病毒复制相关宿主因子,具有较高的抗病毒活性及良好的安全性和耐受性. 核苷类NS5B聚合酶抑制剂sofosbuvir的成功上市,使HCV的治疗取得了突破性进展.本文综述了近年来抗HCV药物的发展情况,总结了各类抗HCV药物的结构、作用机制及相关抗病毒性质.
만성병형간염병독(HCV)감염시전구성적공공위생문제지일,가도치엄중적간병,포괄간경화급간암. 전통적표준치료방안리파위림+취을이순화간우소대병독향응솔저,부작용대,난이유효치료HCV감염. 근년래,다충신류형HCV억제제득이개발,포괄직접항병독약물(DAA)이급숙주파향약물. 저사약물침대병독생명주기중적필수단백,주요포괄NS3/4A단백매、NS5B취합매、NS5A단백혹병독복제상관숙주인자,구유교고적항병독활성급량호적안전성화내수성. 핵감류NS5B취합매억제제sofosbuvir적성공상시,사HCV적치료취득료돌파성진전.본문종술료근년래항HCV약물적발전정황,총결료각류항HCV약물적결구、작용궤제급상관항병독성질.
Chronic hepatitis C virus (HCV) infection is one of global public health problems, and predominantly results in severe hepatic diseases including hepatic cirrhosis and hepatocellular carcinoma. The traditional standard of care for chronic HCV is the combination of ribavirin and pegylated interferon, which is insufficient to cure the HCV infection due to the suboptimal sustained viral response and severe side effects. Recently new therapeutic approaches have been developed, including direct-acting antiviral agents (DAA) and host-targeting agents, which target essential proteins or host factors in HCV life cycle, such as NS3/4A protease, NS5B polymerase and NS5A protein. These agents exhibit high efficacy, improving safety and tolerability. Thus, the approval of the nucleotide polymerase inhibitor sofosbuvir provides a breakthrough therapy against chronic hepatitis C infection. This review describes the current different classes of HCV inhibitors during the last decades, and their chemical structures, mechanisms and related anti-viral property.