人免疫缺陷病毒（HIV）引起的艾滋病是影响人类健康的重大挑战之一。HIV病毒Gp41蛋白N端重复序列区（NHR）是融合抑制剂设计的重要靶点之一。由于目前解析出的Gp41晶体结构主要位于六螺旋核心结构区，缺失NHR下游区域信息，因此NHR下游区的结构及重要生物学功能依然不明确，这大大限制了以其为基础的具有更高活性的新型药物的优化和研发。在前期的工作中，我们课题组发现NHR下游区域可显著增强六螺旋结构的热稳定性并增强与相对应的CHR的亲和性，因此我们推测该区域氨基酸残基对膜融合过程起到关键作用。为了揭示尚未报道的NHR下游区域的具体细节，本研究拟设计可能靶向NHR下游区域的系列多肽，采用圆二色谱等技术检测NHR下游区域与CHR区的结合，同时检测新靶点的抗病毒活性和机制。本项研究有助于深入研究NHR下游区域作用机制，为发展新型的抗HIV多肽药物和小分子药物提供新的理论依据。

Human immunodeficiency virus, the pathogen of acquired immunodeficiency syndrome (AIDS) remains one of the greatest medical challenges in public health. The HIV gp41 N-terminal heptad repeat (NHR) domain serves as an attractive target for development of HIV fusion inhibitors. However, crystal structures of gp41 mainly focus on the 6-HB core region, missing the downstream sequence of NHR, thus, the structural features and biological function of this site are still unknown. It is significantly limited the optimization and development of new drugs with higher activity. In our previous study, we found that the downstream sequence of NHR dramatically enhance the thermostability and conformation of 6-HB structure and the binding affinity of CHR peptides. Thus, we hypothesize that residues in that region play critical roles for Env-mediated cell entry. In order to reveal the details, we will synthesize a series of peptides may target on the NHR downstream region, using the way such as circular dichroism spectroscopy to investigate the interaction between NHR and CHR regions. Then, we will also test their activities of inhibiting HIV entry to study deeply into the mechanism; so as to provide the theoretical and basis on the researches and development of new peptide drugs and small molecular compounds.