摘要
乙肝病毒(hepatitis B virus, HBV)感染严重威胁人类的生命健康。现有治疗药物干扰素和核苷(酸)类似物具有不良反应严重、停药后易反弹以及不同程度的耐药性等问题,并且二者均无法有效清除共价闭合环状DNA(covalently closed circular DNA, cccDNA),从而导致无法彻底治愈乙肝。因此,直接针对HBV自身蛋白或核酸的新药研发仍是公共卫生领域的当务之急。本文精选近10年的研究典例,从药物化学的视角总结了直接靶向HBV小分子抑制剂的前沿进展。
Hepatitis B virus infection is a serious threat to human life and health.The approved anti-HBV drugs including interferons and nucleos(t)ide analogues have serious adverse effect,rebound phenomena after drug withdrawal,and drug resistance.And the cccDNA cannot be completely eliminated by both of them,which is the reason why a complete cure for hepatitis B cannot be achieved.Therefore,developing anti-HBV drugs directly targeting protein or nucleic acid of HBV remains a current public health priority.Based on the analysis of representative literature from the last decade,this article reviews recent developments in small molecule inhibitors directly targeting HBV from a medicinal chemistry perspective.
作者
周加慧
王硕
丁当
徐祥瑞
徐淑静
何勇
刘新泳
展鹏
ZHOU Jia-hui;WANG Shuo;DING Dang;XU Xiang-rui;XU Shu-jing;HE Yong;LIU Xin-yong;ZHAN Peng(Key laboratory of Chemical Biology(Ministry of Education),Department of Medicinal Chemistry,School of Pharmaceutical Sciences,Shandong University,Jinan 250012,China)
出处
《药学学报》
CAS
CSCD
北大核心
2023年第11期3270-3284,共15页
Acta Pharmaceutica Sinica
基金
国家自然科学基金面上项目(82173677)
山东省杰出青年基金(ZR2020JQ31)
山东省重大科技创新工程项目(2019JZZY021011)。
关键词
乙肝病毒
抑制剂
药物靶标
药物化学
药物设计
Hepatitis B virus
inhibitor
drug target
medicinal chemistry
drug design
