Integrative approaches in HIV‐1 non‐nucleoside reverse transcriptase inhibitor design,Wiley Interdisciplinary Reviews: Computational Molecular Science

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Integrative approaches in HIV‐1 non‐nucleoside reverse transcriptase inhibitor design
Wiley Interdisciplinary Reviews: Computational Molecular Science ( IF 16.8 ) Pub Date : 2017-08-30 , DOI: 10.1002/wcms.1328
Vasanthanathan Poongavanam ₁ , Vigneshwaran Namasivayam ₂ , Murugesan Vanangamudi ₃ , Hadi Al Shamaileh ₄ , Rakesh N Veedu _{4,

5} , Jan Kihlberg ₁ , N Arul Murugan ₆

Affiliation

The design of inhibitors for human immunodeficiency virus type‐1 reverse transcriptase (HIV‐1 RT) is one of the most successful approaches for the treatment of HIV infections. Among the HIV‐1 RT inhibitors, non‐nucleoside reverse transcriptase inhibitors (NNRTIs) constitute a prominent drug class, which includes nevirapine, delavirdine, efavirenz, etravirine, and rilpivirine approved for clinical use. However, the efficiency of many of these drugs has been undermined by drug‐resistant variants of HIV‐1 RT, and it therefore becomes inevitable to design novel drugs to cope with resistance. Here, we discuss various drug design strategies, which include traditional medicinal chemistry, computational chemistry, and chemical biology approaches. In particular, computational modeling approaches, including machine learning, empirical descriptors‐based, force‐field, ab initio, and hybrid quantum mechanics/molecular mechanics‐based methods are discussed in detail. We foresee that these methods will have a major impact on efforts to guide the design and discovery of the next generation of NNRTIs that combat RT multidrug resistance. WIREs Comput Mol Sci 2018, 8:e1328. doi: 10.1002/wcms.1328

中文翻译：

HIV-1非核苷逆转录酶抑制剂设计中的整合方法

设计用于人类免疫缺陷病毒1型逆转录酶（HIV-1 RT）的抑制剂是治疗HIV感染最成功的方法之一。在HIV-1 RT抑制剂中，非核苷类逆转录酶抑制剂（NNRTIs）构成了突出的药物类别，其中包括获准临床使用的奈韦拉平，地拉夫定，依非韦伦，依曲韦林和利比韦林。但是，HIV-1 RT的耐药变体削弱了许多这类药物的功效，因此，设计新的药物来应对耐药性已成为必然。在这里，我们讨论了各种药物设计策略，包括传统的药物化学，计算化学和化学生物学方法。特别是计算建模方法，包括机器学习，基于经验描述符的，从头开始，并详细讨论了基于混合量子力学/分子力学的方法。我们预见到，这些方法将对指导对抗RT多药耐药性的下一代NNRTI的设计和发现的努力产生重大影响。电线计算科学2018，8：e1328。doi：10.1002 / wcms.1328

更新日期：2017-08-30

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