逆转录酶
灵活性(工程)
人类免疫缺陷病毒(HIV)
药物发现
药品
抗药性
计算生物学
药物开发
机制(生物学)
生物
医学
药理学
病毒学
生物信息学
遗传学
核糖核酸
统计
数学
基因
哲学
认识论
作者
Ge‐Fei Hao,Sheng-Gang Yang,Guang‐Fu Yang
标识
DOI:10.2174/138161282005140214163439
摘要
Reverse transcriptase (RT) is one of the most important targets for HIV drug discovery. However, the emergence of resistant mutants has become one of the biggest challenges in HIV-1 RT drug discovery/development and attracted great research interests worldwide. It is particularly important to develop novel anti-HIV-1 RT agents that have improved potency and efficacy against the wild-type (WT) RT, but also target resistant RT forms. Previous crystal complex structures of HIV-1 RT revealed the interaction mechanism between the enzyme and inhibitors, which promoted the exploitation of inhibitor that had sufficient conformational flexibility to combat resistance. Hence, the potential flexibility of a drug should be part of the strategy considered in the early stages of designing drugs that are intended to be broadly effective against mutated targets associated with drug resistance. This review provides an overview of the state of the art in this field, including design strategies and challenges for medicinal chemists. Keywords: HIV Reverse transcriptase, conformational flexibility, drug resistance.
科研通智能强力驱动
Strongly Powered by AbleSci AI