Min Yuan-Qin, Mo Qiong, Wang Jun, Deng Fei, Wang Hualin, Ning Yun-Jia
State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China.
University of Chinese Academy of Sciences, Beijing, China.
Front Microbiol. 2020 Sep 29;11:587317. doi: 10.3389/fmicb.2020.587317. eCollection 2020.
The emerging coronavirus disease (COVID-19) caused by SARS-CoV-2 has led to social and economic disruption globally. It is urgently needed to understand the structure and function of the viral proteins for understanding of the viral infection and pathogenesis and development of prophylaxis and treatment strategies. Coronavirus non-structural protein 1 (nsp1) is a notable virulence factor with versatile roles in virus-host interactions and exhibits unique characteristics on sequence, structure, and function mode. However, the roles and characteristics of SARS-CoV-2 nsp1 are currently unclear. Here, we analyze the nsp1 of SARS-CoV-2 from the following perspectives: (1) bioinformatics analysis reveals that the novel nsp1 is conserved among SARS-CoV-2 strains and shares significant sequence identity with SARS-CoV nsp1; (2) structure modeling shows a 3D α/β-fold of SARS-CoV-2 nsp1 highly similar to that of the SARS-CoV homolog; (3) by detailed, functional review of nsp1 proteins from other coronaviruses (especially SARS-CoV) and comparison of the protein sequence and structure, we further analyzed the potential roles of SARS-CoV-2 nsp1 in manipulating host mRNA translation, antiviral innate immunity and inflammation response and thus likely promoting viral infection and pathogenesis, which are merited to be tested in the future. Finally, we discussed how understanding of the novel nsp1 may provide valuable insights into the designs of drugs and vaccines against the unprecedented coronavirus pandemic.
由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的新型冠状病毒病（COVID-19）已在全球范围内导致社会和经济混乱。迫切需要了解病毒蛋白的结构和功能，以理解病毒感染和发病机制，并制定预防和治疗策略。冠状病毒非结构蛋白1（nsp1）是一种显著的毒力因子，在病毒与宿主的相互作用中具有多种作用，并且在序列、结构和功能模式上表现出独特的特征。然而，目前SARS-CoV-2 nsp1的作用和特征尚不清楚。在此，我们从以下几个方面分析SARS-CoV-2的nsp1：（1）生物信息学分析表明，新型nsp1在SARS-CoV-2毒株中保守，并且与SARS-CoV的nsp1具有显著的序列同一性；（2）结构建模显示，SARS-CoV-2 nsp1的三维α/β折叠与SARS-CoV同源物高度相似；（3）通过对其他冠状病毒（特别是SARS-CoV）的nsp1蛋白进行详细的功能综述，并比较蛋白序列和结构，我们进一步分析了SARS-CoV-2 nsp1在操纵宿主mRNA翻译、抗病毒固有免疫和炎症反应中可能发挥的潜在作用，从而可能促进病毒感染和发病机制，这些有待未来进行验证。最后，我们讨论了对新型nsp1的理解如何为针对这场前所未有的冠状病毒大流行的药物和疫苗设计提供有价值的见解。
