HIV-1病毒与细胞融合过程中，其表面包膜蛋白gp41的N末端重复序列会形成一个空间上对称的螺旋三聚体。以该三聚体为靶标，设计多价药物能有效提高与靶标的亲和力。本研究全新提出，基于核酸二级结构的多样性和自组装性，设计不同价态和结构的多价类核酸融合抑制剂。通过在一条寡核苷酸序列上分区设计碱基排列（二级结构组装区、连接臂区、活性区），就可以通过核酸二级结构组装富集多个活性区，活性区进一步形成活性构象（近年新发现的含芳香基团的核酸螺旋），从而获得多价目标分子。初步研究结果提示，设计的一个多价分子表现出了与上市药物T20相当的细胞活性，远高于其单价态分子。本研究设计的多价核酸抑制剂结构完全不同于以往药物，各价态结构的实现均基于核酸二级结构组装而无需额外的化学修饰和共价连接方式，从中有望发现高活性、新结构HIV-1融合抑制剂。本研究的设计思想也将为其他核酸类药物的多价策略提供新思路和参考实例。

The N-terminal heptad repeat (NHR) domain in HIV-1 envelop glycoprotein gp41 can fold a symmetrical triple stranded coiled-coil structure during the course of fusion between virus and target cells. Design of multivalent drug targeting to NHR triple structure can greatly improve its affinity. We put forward in this paper, based on the self-assembly and diversity of nucleic acid high structure, we can design novel multivalent HIV-1 fusion inhibitor with different structures. By designing the base composition in different and specific domains (high structure assembly domain, conjunction domain and activity domain) in one ODN, we can easily congregate multi activity domains in one assembled high structure. With the activity domains forming into active conformation (hydrophobic modified DNA helix), we get target complex structure. One of our designed multivalent molecular showed comparative activity to a marketed drug T20 in the anti-cell fusion test, and is much higher than its monovalent structure. Multivalent inhibitors of nucleic acid in this paper are unique structures to former drugs, and this strategy does not need extra chemical modification. It’s hopeful to discovery novel anti-HIV-1 fusion drug. This research may provide new strategy for designing other multivalent nucleic acid drugs.