摘要
HIV-1逆转录酶(RT)在病毒复制周期具有重要作用,因此多年来一直是抗病毒药物研发的热点。目前上市的HIV-1 RT抑制剂分为核苷类抑制剂(NRTIs)和非核苷类抑制剂(NNRTIs),它们活性高、疗效好,但同时存在长期服用不良反应大、易产生耐药性等问题。因此,研究新作用机制的RT抑制剂十分必要。近几年,核苷酸竞争性抑制剂、逆转录酶定向的突变诱导抑制剂、引物/模板-竞争性逆转录酶抑制剂、聚合酶-RNase H双重抑制剂、逆转录起始过程抑制剂、肽类抑制剂等新作用机制的HIV-1 RT抑制剂见诸报道,为抗艾滋病药物的研发带来了新的曙光。本文重点介绍这方面的研究进展。
HIV-1 reverse transcriptase(RT) plays an important role in HIV-1 life cycle. At present, the listed NRTIs and NNRTIs targeting the RT showed high efficiency as clinical first-line drugs. However, the rapid emergence of multidrug-resistant viruses and significant cumulative drug toxicities compromises antiretroviral therapy efficacy and limits therapeutic options. Therefore, there is an urgent demand for new types of RT inhibitors with novel mechanism of action to address this challenge. In recent years, additional inhibitors with novel mechanism of action have been reported, including nucleic acid competitive inhibitors, reverse transcriptase-directed mutagenesis inhibitors, primers/templates-competitive reverse transcriptase inhibitors, polymerase-RNase H inhibitors, reverse transcription initiation process inhibitors, peptide inhibitors etc., which have brought new hope to the development of novel anti-HIV drugs. This article focuses on the development of these inhibitors.
作者
周忠霞
孙林
康东伟
陈子慧
唐苗苗
李思雨
展鹏
刘新泳
ZHOU Zhong-xia;SUN Lin;KANG Dong-wei;CHEN Zi-hui;TANG Miao-miao;LI Si-yu;ZHAN Peng;LIU Xin-yong(Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Ji 'nan 250012, China)
出处
《药学学报》
CAS
CSCD
北大核心
2018年第5期691-700,共10页
Acta Pharmaceutica Sinica
基金
国家自然科学基金资助项目(81573347
81420108027)
2017年山东省重点研发计划资助项目(2017CXGC1401)