目前美国FDA批准的艾滋病药物都主要在HIV感染靶细胞过程中或进入靶细胞后发挥作用，它们只是被动的防御：抑制病毒侵染和复制，并不能在没有靶细胞的情况下主动进攻和灭活病毒。在前期工作中，我们课题组设计了一种新型HIV蛋白类灭活剂DLP，该灭活剂可以特异性作用于HIV-1的gp120和gp41，并使其在没有靶细胞的情况下被快速灭活。但蛋白类灭活剂只能用于注射，不能口服，影响其临床应用。在本课题中，我们拟根据之前的经验设计新型的小分子类灭活剂，该小分子灭活剂预期靶点为gp120与gp41，可主动进攻灭活病毒，也克服蛋白药物不能口服的缺点，显著提高使用的依从性。同时，我们也将利用生物化学、分子生物学及细胞生物学等手段对该新型灭活剂作用机制开展深入的研究。该类研究目前在国际上尚未见报道，具有创新性。本课题的开展将为最终获得活性更高、成药性更强、具有我国自主知识产权的新型抗HIV药物提供重要理论基础。

At present, most FDA approved anti-HIV drugs act inside or on surface of the target cell to inhibit HIV infection. Therefore, these drugs inhibited viral infection and replication that are passive defense strategy, but none can actively attack virus in the absence of targeted cells. In our previous study, we designed and got a protein inactivator DLP as a new class of anti-HIV drug. DLP can directly inactivate HIV virion in the absence of host cells by specifically binding to gp120 and gp41 of HIV-1. However, protein inactivators were constrained due to its lack of oral bioavailability, resulting in their inability of clinical application. In present study, we will first test a series of small molecular compounds that target gp120 and gp41 as well as high effective inactivate HIV-1 under combination application. Then, we will synthesis a series of monomeric compounds binding both gp120 and gp41 based on the structure of each pair small molecular compounds. Subsequently, two or three with high effective inactivation will be selected as lead drugs for designing、synthetising and biological evaluation of related derivatives. The small molecular HIV-1 inactivators with higher activity and stronger druggability will be expected to obtain, providing theoretical foundation for developing novel anti-HIV drug with Chinese own intellectual property right.