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HIV-1 逆转录酶抑制剂的最新研究进展和分子对接研究。

Current insights and molecular docking studies of HIV-1 reverse transcriptase inhibitors.

机构信息

Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, Bathinda, Punjab, India.

Department of Pharmaceutical Sciences, Bioorganic and Medicinal Chemistry Research Laboratory, Sam Higginbottom University of Agriculture, Technology and Sciences, Prayagraj, Uttar Pradesh, India.

出版信息

Chem Biol Drug Des. 2024 Jan;103(1):e14372. doi: 10.1111/cbdd.14372. Epub 2023 Oct 10.

Abstract

Human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS), a lethal disease that is prevalent worldwide. According to the Joint United Nations Programme on HIV/AIDS (UNAIDS) data, 38.4 million people worldwide were living with HIV in 2021. Viral reverse transcriptase (RT) is an excellent target for drug intervention. Nucleoside reverse transcriptase inhibitors (NRTIs) were the first class of approved antiretroviral drugs. Later, a new type of non-nucleoside reverse transcriptase inhibitors (NNRTIs) were approved as anti-HIV drugs. Zidovudine, didanosine, and stavudine are FDA-approved NRTIs, while nevirapine, efavirenz, and delavirdine are FDA-approved NNRTIs. Several agents are in clinical trials, including apricitabine, racivir, elvucitabine, doravirine, dapivirine, and elsulfavirine. This review addresses HIV-1 structure, replication cycle, reverse transcription, and HIV drug targets. This study focuses on NRTIs and NNRTIs, their binding sites, mechanisms of action, FDA-approved drugs and drugs in clinical trials, their resistance and adverse effects, their molecular docking studies, and highly active antiretroviral therapy (HAART).

摘要

人类免疫缺陷病毒(HIV)会引起获得性免疫缺陷综合征(AIDS),这是一种致命的疾病,在全球范围内普遍存在。根据联合国艾滋病规划署(UNAIDS)的数据,2021 年全球有 3840 万人携带 HIV。病毒逆转录酶(RT)是药物干预的极佳靶点。核苷类逆转录酶抑制剂(NRTIs)是第一批获得批准的抗逆转录病毒药物。后来,一种新型的非核苷类逆转录酶抑制剂(NNRTIs)被批准作为抗 HIV 药物。齐多夫定、地达诺辛和司他夫定是 FDA 批准的 NRTIs,而奈韦拉平、依法韦仑和依法韦仑是 FDA 批准的 NNRTIs。一些药物正在临床试验中,包括阿匹卡韦、拉米夫定、elvucitabine、多拉韦林、达匹韦林和埃拉夫丁。这篇综述讨论了 HIV-1 的结构、复制周期、逆转录以及 HIV 药物靶点。本研究重点关注 NRTIs 和 NNRTIs、它们的结合位点、作用机制、FDA 批准的药物和临床试验中的药物、它们的耐药性和不良反应、它们的分子对接研究以及高效抗逆转录病毒疗法(HAART)。

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