新型冠状病毒NSP6与ATPases/SIGMAR1复合物结构和机制研究

新型冠状病毒SARS-CoV-2导致COVID-19呼吸系统疾病和高死亡率。最近，研究人员利用亲和纯化质谱鉴定了与SARS-CoV-2 NSP6相互作用的4个人源蛋白，包括ATPases家族的三个亚基和SIGMAR1。冠状病毒NSP6是一个多次跨膜蛋白，涉及病毒诱导双膜泡形成，诱导细胞自噬和限制自噬体膨胀。这四个宿主蛋白涉及多种重要生物学过程，如能量合成和细胞自噬等，并在病毒周期中发挥作用，是抗病毒药物重要靶点。然而，SARS-CoV-2 NSP6与ATPases/SIGMAR1互作形成的复合物结构和作用机制还不清楚。本项目拟借助结构生物学、生物化学、分子生物学等多种技术手段探究SARS-CoV-2 NSP6分别与ATPases/ SIGMAR1形成的每个复合物的结构和作用机制。该研究有望揭示新型冠状病毒与宿主互作的新机制，并为开发抗冠状病毒新的关键治疗靶点提供重要参考。

The novel coronavirus SARS-CoV-2 causes COVID-19 respiratory diseases and high mortality. It’s recently reported four human proteins, including three subunits of ATPases and SIGMAR1, which interact with SARS-CoV-2 nonstructural protein 6 (NSP6), were identified by affinity purification-mass spectrometry. Coronavirus NSP6 is a multiple transmembrane protein involved in virus-induced double vesicle formation, induction of autophagy and restriction of autophagosome expansion. The four host proteins are involved in many important biological processes, such as energy synthesis and autophagy, play roles in the virus cycle, and are important targets of antiviral drugs. However, the structures and mechanisms of the complexes formed by the interactions of SARS-CoV-2 NSP6 and ATPases/SIGMAR1 are not clear. In this study, we plan to explore the structure and mechanism of each complex separately formed by SARS-CoV-2 NSP6 and each of ATPases/SIGMAR1 by structural biology, biochemistry, molecular biology, and so on. This study is expected to reveal new mechanism of the interaction between novel coronavirus and host, and provide important reference for the development of new key therapeutic targets against coronavirus.