Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, 250012, Jinan, Shandong, PR China.
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, 250012, Jinan, Shandong, PR China; China-Belgium Collaborative Research Center for Innovative Antiviral Drugs of Shandong, Province, 44 West Culture Road, 250012, Jinan, Shandong, PR China.
Eur J Med Chem. 2021 May 5;217:113380. doi: 10.1016/j.ejmech.2021.113380. Epub 2021 Mar 15.
A capsid is the protein shell of a virus, encircling its genetic material. The HIV capsid is erected from a single protein, known as capsid protein. The capsid of HIV-1 significantly involved in many processes of the virus life cycle, which makes it as a novel target for the new inhibitors. Recently many novel HIV-1 inhibitors binding to capsid proteins have been reported successfully. Most of these inhibitors can inhibit or accelerate the disassembly or assembly of the capsid, and some of them can inhibit reverse transcription. Unfortunately, none of them are currently approved by U.S. FDA. However, GS-6207, an inhibitor binds to the NTD-CTD interface with potent antiviral activity and the long metabolic cycle, is expected to be the first approved drug targeting HIV-1 capsid. Herein, we provide a concise report focusing on the recent prospective of HIV-1 capsid inhibitors in medicinal chemistry in order to enlighten drug design.
衣壳是病毒的蛋白质外壳，环绕着其遗传物质。HIV 的衣壳由一种称为衣壳蛋白的单一蛋白质构成。HIV-1 的衣壳在病毒生命周期的许多过程中都有重要参与，这使其成为新抑制剂的一个新靶点。最近，已有许多成功报道了结合衣壳蛋白的新型 HIV-1 抑制剂。这些抑制剂大多数可以抑制或加速衣壳的解体或组装，其中一些还可以抑制逆转录。不幸的是，目前它们都没有被美国 FDA 批准。然而，GS-6207 是一种与 NTD-CTD 界面结合的抑制剂，具有很强的抗病毒活性和长代谢周期，有望成为第一个获批的靶向 HIV-1 衣壳的药物。本文旨在为药物设计提供启示，简要介绍了衣壳抑制剂在药物化学方面的最新研究进展。
