University of Delaware, Department of Chemistry and Biochemistry, Newark, DE, United States; Pittsburgh Center for HIV Protein Interactions, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.
University of Delaware, Department of Chemistry and Biochemistry, Newark, DE, United States.
Curr Opin Virol. 2021 Jun;48:57-64. doi: 10.1016/j.coviro.2021.03.005. Epub 2021 Apr 23.
HIV-1 is the causative agent of acquired immunodeficiency syndrome (AIDS), a global pandemic that has claimed 32.7 million lives since 1981. Despite decades of research, there is no cure for the disease, with 38 million people currently infected with HIV. Attractive therapeutic targets for drug development are mature HIV-1 capsids, immature Gag polyprotein assemblies, and Gag maturation intermediates, although their complex architectures, pleomorphism, and dynamics render these assemblies challenging for structural biology. The recent development of integrative approaches, combining experimental and computational methods has enabled atomic-level characterization of structures and dynamics of capsid and Gag assemblies, and revealed their interactions with small-molecule inhibitors and host factors. These structures provide important insights that will guide the development of capsid and maturation inhibitors.
HIV-1 是获得性免疫缺陷综合征（AIDS）的病原体，自 1981 年以来，这种全球性大流行已导致 3270 万人死亡。尽管经过几十年的研究，仍然没有治愈这种疾病的方法，目前有 3800 万人感染了 HIV。对于药物开发来说，有吸引力的治疗靶点是成熟的 HIV-1 衣壳、不成熟的 Gag 多聚蛋白组装体和 Gag 成熟中间体，尽管它们的复杂结构、多态性和动力学使这些组装体成为结构生物学的挑战。最近综合方法的发展，结合实验和计算方法，使衣壳和 Gag 组装体的结构和动力学的原子水平表征成为可能，并揭示了它们与小分子抑制剂和宿主因子的相互作用。这些结构提供了重要的见解，将指导衣壳和成熟抑制剂的开发。
