美国波士顿儿童医院Bing Chen研究组揭示D614G突变对SARS-CoV-2蛋白结构的影响。相关论文于2021年3月16日在线发表于国际学术期刊《科学》。

据研究人员介绍，在SARS-CoV-2突刺（S）蛋白中，第614位的甘氨酸替代为天冬氨酸似乎促进了病毒的快速传播。G614菌株及其最近的变体是现在主要的传播变体。

研究人员报道了全长G614 S三聚体的冷冻电镜结构，该结构采用三种不同的预融合构象，主要区别在于一个受体结合域的位置不同。D614 S三聚体中无序的环在G614突刺中前体内的结构域之间楔入。这种增加的相互作用似乎可以防止G614三聚体过早解离，有效地增加功能性突刺的数量并增强感染性，以及调节膜融合的结构重排。

这些发现扩展了人们对病毒进入的理解，并提出了用于疫苗开发的改进免疫原。 

附：英文原文

Title: Structural impact on SARS-CoV-2 spike protein by D614G substitution

Author: Jun Zhang, Yongfei Cai, Tianshu Xiao, Jianming Lu, Hanqin Peng, Sarah M. Sterling, Richard M. Walsh, Sophia Rits-Volloch, Haisun Zhu, Alec N. Woosley, Wei Yang, Piotr Sliz, Bing Chen

Issue&Volume: 2021/03/16

Abstract: Substitution for aspartic acid by glycine at position 614 in the spike (S) protein of severe acute respiratory syndrome coronavirus 2 appears to facilitate rapid viral spread. The G614 strain and its recent variants are now the dominant circulating forms. We report here cryo-EM structures of a full-length G614 S trimer, which adopts three distinct prefusion conformations differing primarily by the position of one receptor-binding domain. A loop disordered in the D614 S trimer wedges between domains within a protomer in the G614 spike. This added interaction appears to prevent premature dissociation of the G614 trimer, effectively increasing the number of functional spikes and enhancing infectivity, and to modulate structural rearrangements for membrane fusion. These findings extend our understanding of viral entry and suggest an improved immunogen for vaccine development.

DOI: 10.1126/science.abf2303

Source: https://science.sciencemag.org/content/early/2021/03/16/science.abf2303