Institute of Biomedical Chemistry, 10 building 8, Pogodinskaya st., Moscow 119121, Russia.
Molecules. 2018 Apr 19;23(4):956. doi: 10.3390/molecules23040956.
Research and development of new antiretroviral agents are in great demand due to issues with safety and efficacy of the antiretroviral drugs. HIV reverse transcriptase (RT) is an important target for HIV treatment. RT inhibitors targeting early stages of the virus-host interaction are of great interest for researchers. There are a lot of clinical and biochemical data on relationships between the occurring of the single point mutations and their combinations in the pol gene of HIV and resistance of the particular variants of HIV to nucleoside and non-nucleoside reverse transcriptase inhibitors. The experimental data stored in the databases of HIV sequences can be used for development of methods that are able to predict HIV resistance based on amino acid or nucleotide sequences. The data on HIV sequences resistance can be further used for (1) development of new antiretroviral agents with high potential for HIV inhibition and elimination and (2) optimization of antiretroviral therapy. In our communication, we focus on the data on the RT sequences and HIV resistance, which are available on the Internet. The experimental methods, which are applied to produce the data on resistance, the known data on their concordance, are also discussed.
由于抗逆转录病毒药物的安全性和疗效问题,新的抗逆转录病毒药物的研发需求巨大。HIV 逆转录酶(RT)是 HIV 治疗的重要靶点。针对病毒-宿主相互作用早期阶段的 RT 抑制剂引起了研究人员的极大兴趣。在 HIV 多聚酶基因中,发生单点突变及其组合与特定 HIV 变异体对核苷和非核苷逆转录酶抑制剂的耐药性之间存在大量临床和生化数据。存储在 HIV 序列数据库中的实验数据可用于开发基于氨基酸或核苷酸序列预测 HIV 耐药性的方法。HIV 序列耐药性的数据可进一步用于(1)开发具有高抑制和消除 HIV 潜力的新型抗逆转录病毒药物,以及(2)优化抗逆转录病毒治疗。在我们的交流中,我们专注于互联网上可用的 RT 序列和 HIV 耐药性数据。还讨论了用于产生耐药性数据的实验方法及其已知的一致性数据。