新型冠状病毒及其受体蛋白胞内运输的分子机制研究

严重急性呼吸综合征冠状病毒-2（SARS-CoV-2）表面的刺突蛋白（Spike，S）识别靶细胞受体并与之结合是病毒侵入宿主细胞的第一步，也是预防和治疗病毒感染的关键靶点。近年来，研究发现SNX27作为逆向囊泡转运复合体（Retromer）的配体将被内吞的膜表面蛋白重新运送回细胞膜，并行使其生物功能。本项目前期研究发现，SNX27-PDZ结构域能够结合ACE2蛋白。为了进一步阐明受体蛋白转运的分子机制，本项目以SNX27与Retromer复合体作为切入点，在分子和细胞水平明确SNX27与Retromer复合体在ACE2蛋白细胞表面稳态中的作用，揭示SNX27与Retromer复合体参与病毒胞内运输的分子机制。通过以上研究，为抗病毒药物及疫苗的研发提供潜在的靶点，也为新型冠状病毒的侵袭奠定防控的理论策略。

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spikes protein recognize and bind to target cell receptors, which is the first step of virus invasion into host cells, and is also a key target for prevention and treatment of viral infection. In recent years, it has been found that SNX27 is a ligand of a Retromer that can be transported back to the cell membrane by endocytic membrane surface proteins and perform its biological functions. The preliminary study of this project found that the SNX27-PDZ domain had a certain binding effect with ACE2 protein. In order to further clarify the molecular mechanism of receptor protein transport, this project takes SNX27 and Retromer complex as the breakthrough point to clarify the role of SNX27 and Retromer complex in ACE2 protein cell surface homeostasis at the molecular and cellular levels and reveal the molecular mechanism of SNX27 and Retromer complex involved in intracellular viral transport. The above studies provide potential targets for the research and development of antiviral drugs and vaccines, and also lay a theoretical strategy for the prevention and control of SARS-CoV-2.