避免 HIV 逆转录酶的耐药性。
Avoiding Drug Resistance in HIV Reverse Transcriptase.
机构信息
Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30322, United States.
Children's Healthcare of Atlanta, Atlanta, Georgia 30307, United States.
出版信息
Chem Rev. 2021 Mar 24;121(6):3271-3296. doi: 10.1021/acs.chemrev.0c00967. Epub 2021 Jan 28.
Abstract
HIV reverse transcriptase (RT) is an enzyme that plays a major role in the replication cycle of HIV and has been a key target of anti-HIV drug development efforts. Because of the high genetic diversity of the virus, mutations in RT can impart resistance to various RT inhibitors. As the prevalence of drug resistance mutations is on the rise, it is necessary to design strategies that will lead to drugs less susceptible to resistance. Here we provide an in-depth review of HIV reverse transcriptase, current RT inhibitors, novel RT inhibitors, and mechanisms of drug resistance. We also present novel strategies that can be useful to overcome RT's ability to escape therapies through drug resistance. While resistance may not be completely avoidable, designing drugs based on the strategies and principles discussed in this review could decrease the prevalence of drug resistance.
摘要
HIV 逆转录酶（RT）是一种在 HIV 复制周期中起主要作用的酶，一直是抗 HIV 药物开发努力的关键目标。由于病毒的高度遗传多样性，RT 中的突变可赋予对各种 RT 抑制剂的耐药性。随着耐药突变的流行率不断上升，有必要设计出不易产生耐药性的药物。在这里，我们对 HIV 逆转录酶、当前的 RT 抑制剂、新型 RT 抑制剂以及耐药机制进行了深入的综述。我们还提出了一些新的策略，这些策略可能有助于克服 RT 通过耐药性逃避治疗的能力。虽然耐药性可能无法完全避免，但根据本综述中讨论的策略和原则设计药物可以降低耐药性的流行率。
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