Computational drug design strategies applied to the modelling of human immunodeficiency virus-1 reverse transcriptase inhibitors.
Computational drug design strategies applied to the modelling of human immunodeficiency virus-1 reverse transcriptase inhibitors.
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DOI：
10.1590/0074-02760150239
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发表时间：
2015-11
影响因子：
2.8
通讯作者：
Caffarena ER
中科院分区：
文献类型：
--
作者：
Santos LH;Ferreira RS;Caffarena ER
逆转录酶（RT）是人类免疫缺陷病毒（HIV）-1生命周期中的多功能酶，并且代表针对HIV-1感染的药物发现努力的主要靶标。核苷类逆转录酶抑制剂（NRTI）和非核苷类逆转录酶抑制剂（non-nucleotide transcriptase inhibitors，non-NRTI）是目前与其他抗HIV药物联合应用的两大类逆转录酶抑制剂。然而，耐药病毒株的迅速出现限制了抗HIV药物的成功率。计算方法是药物设计过程的重要组成部分，也是研究耐药性不可或缺的。本文综述了近年来计算机辅助药物设计在抗HIV-1逆转录病毒药物合理设计中的研究进展，包括分子对接、分子动力学、自由能计算、定量构效关系、药效团建模以及吸收、分布、代谢、排泄和毒性预测等。这些方法的成功应用也得到了强调。
Reverse transcriptase (RT) is a multifunctional enzyme in the human immunodeficiency virus (HIV)-1 life cycle and represents a primary target for drug discovery efforts against HIV-1 infection. Two classes of RT inhibitors, the nucleoside RT inhibitors (NRTIs) and the nonnucleoside transcriptase inhibitors are prominently used in the highly active antiretroviral therapy in combination with other anti-HIV drugs. However, the rapid emergence of drug-resistant viral strains has limited the successful rate of the anti-HIV agents. Computational methods are a significant part of the drug design process and indispensable to study drug resistance. In this review, recent advances in computer-aided drug design for the rational design of new compounds against HIV-1 RT using methods such as molecular docking, molecular dynamics, free energy calculations, quantitative structure-activity relationships, pharmacophore modelling and absorption, distribution, metabolism, excretion and toxicity prediction are discussed. Successful applications of these methodologies are also highlighted.