SARS-CoV-2核衣壳蛋白相分离研究进展

Research Progress on the Phase Separation of SARS-CoV-2 Nucleocapsid Protein

新型冠状病毒(Severe acute respiratory syndromes coronavirus 2,SARS-CoV-2)感染引发的新型冠状病毒肺炎(Corona Virus Disease 19,COVID-19)目前正在全球范围内对公众健康和安全造成重大威胁。冠状病毒的核衣壳(Nucleocapsid,N)蛋白主要作为病毒关键结构蛋白,负责与病毒基因组RNA结合组装成核衣壳,并进一步与膜(Membrane,M)蛋白结合组装成病毒体(Virion)。此外,N蛋白兼具调节蛋白功能,在抑制宿主天然免疫反应以及通过结合复制-转录复合体(Replication transcription complex,RTC)促进病毒转录和复制等过程中也发挥了重要作用。最近一些研究相继揭示了SARS-CoV-2 N蛋白具有与RNA或其他蛋白发生液-液相分离(Liquid-liquid phase separation,LLPS)的能力,并且N蛋白的相分离正逐渐被证实在其发挥结构蛋白和调节蛋白功能的过程中均具有重要作用。本文主要就SARS-CoV-2 N蛋白相分离的最新研究成果进行综述,并就N蛋白相分离作为治疗COVID-19的潜在药物靶点加以讨论。

COVID-19 pandemic,caused by infection of severe acute respiratory syndrome Coronavirus 2(SARS-CoV-2),is an ongoing and severe threat to public health and safety.The Coronavirus nucleocapsid(N)protein mainly functions as a key structural protein,responsible for binding and packaging viral genome RNA into nucleocapsid and recruiting membrane(M)protein for virion assembly.In addition,the N protein functions as a regulatory protein and plays important roles in suppression of the host innate immune response,and localization with replication transcription complex(RTC)to facilitate viral transcription and replication.Accumulating evidences have emerged recently that SARS-CoV-2 N protein undergoes liquid-liquid phase separation(LLPS)with RNA or other proteins.Importantly,phase separation of the N protein has been shown to be essential for its structural and regulatory roles.Here,we summarize recent research progress on the phase separation of SARS-CoV-2 N protein.The potential of the phase separation of the N protein as a therapeutic drug targets is also discussed.