Inhibitors and Probes of HIV-1 Cell Fusion

NIDDK的LBC天然产物化学部有几个正在进行的项目，其长期目标是鉴定和设计HIV-1包膜介导的细胞融合的抑制剂和探针。这些包括设计和开发具有抑制剂和免疫原双重功能的新的gp 41衍生肽和蛋白质，发现和高分辨率结构表征新的碳水化合物结合蛋白，其通过碳水化合物介导的与gp 120/gp 41的相互作用有效地抑制HIV-1进入，发现HIV-1融合的天然产物抑制剂，以及HIV-1包膜-辅助受体相互作用的结构和机制研究。虽然在开发治疗方法和延长艾滋病毒感染者的预期寿命方面取得了很大进展，但我们没有治愈这种疾病的方法，仍然存在许多挑战，包括耐药性的发展以及治疗的成本和可用性。该研究计划旨在通过发现或设计新型抑制剂以及通过增加对病毒进入过程的了解来克服其中一些挑战。

The Natural Products Chemistry Section, LBC, NIDDK has several ongoing projects whose long term aim is to identify and design inhibitors and probes of HIV-1 Envelope-mediated cell fusion. These include the design and development of new gp41-derived peptides and proteins that have dual functions as inhibitors and immunogens, discovery and high resolution structural characterization of new carbohydrate binding proteins that potently inhibit HIV-1 Entry through carbohydrate-mediated interactions with gp120/gp41, discovery of natural product inhibitors of HIV-1 fusion, and structural and mechanistic studies of HIV-1 Envelope-coreceptor interactions. Though great progress has been achieved in developing treatments for and extending the life expectancies of HIV infected individuals, we do not have a cure for this disease and many challenges remain including the development of drug resistance and the cost and availability of treatments. This research program aims to overcome some of these challenges through discovery or design of novel classes of inhibitors and through increased understanding of the viral entry process.