HIV-1非核苷类逆转录酶抑制剂的研究进展(2016-2021)

Recent advance of HIV-1 non-nucleoside reverse transcriptase inhibitors (2016-2021)

HIV-1非核苷类逆转录酶抑制剂(NNRTIs)作为高效抗逆转录病毒疗法的重要组分之一,在过去二十多年抗艾斗争中发挥着重要作用。尽管如此,目前NNRTIs在临床应用中仍然显现出诸多问题,如耐药基因屏障低、水溶性不佳、严重的不良反应等。因此,开发新一代抗耐药相关突变、溶解性优良且毒副作用小的新型抑制剂迫在眉睫。近年来,科研工作者们为早日攻破艾滋病治疗难题,一直致力于NNRTIs的研究与开发,多个研究小组经合理药物设计发现了种类繁多、化学结构多样的NNRTIs。本文作者主要就近年来(2016.01-2021.08)NNRTIs的发现与结构修饰的研究进展进行综述,以期对NNRTIs的研究有所启示。

Over the past twenty-odd years, HIV-1 non-nucleoside reverse transcriptase inhibitors(NNRTIs),as one of the important components of highly active antiretroviral therapy(HAART),have played an indispensable role in the fighting against AIDS.However, there are still many problems in the clinical application of NNRTIs, such as low resistance gene barriers, poor water solubility and severe side effects.Therefore, it is urgent to develop a new generation of inhibitors with anti-resistance-associated mutation, good solubility and low toxicity.In recent years, to solve the problem of AIDS as quickly as possible, researchers have made great efforts for the extensive development of NNRTIs.Up to now, based on rational drug design, many research groups have discovered a wide range of NNRTIs with diverse chemical structures.In this paper, the discovery and structural modification of NNRTIs in recent six years were reviewed, providing some enlightenment for the research of NNRTIs.