美国马萨诸塞大学医学院Jeremy Luban等研究人员合作完成对SARS-CoV-2突刺蛋白D614G变异体的结构和功能分析。相关论文于2020年9月15日在线发表在《细胞》杂志上。

Title: Structural and Functional Analysis of the D614G SARS-CoV-2 Spike Protein Variant

Author: Leonid Yurkovetskiy, Xue Wang, Kristen E. Pascal, Christopher Tomkins-Tinch, Thomas Nyalile, Yetao Wang, Alina Baum, William E. Diehl, Ann Dauphin, Claudia Carbone, Kristen Veinotte, Shawn B. Egri, Stephen F. Schaffner, Jacob E. Lemieux, James Munro, Ashique Rafique, Abhi Barve, Pardis C. Sabeti, Christos A. Kyratsous, Natalya Dudkina, Kuang Shen, Jeremy Luban

Issue&Volume: 2020-09-15

Abstract: The SARS-CoV-2 spike (S) protein variant D614G supplanted the ancestral virus worldwide, reaching near fixation in a matter of months. Here we show that D614G was more infectious than the ancestral form on human lung cells, colon cells, and on cells rendered permissive by ectopic expression of human ACE2 or of ACE2 orthologs from various mammals, including Chinese rufous horseshoe bat and Malayan pangolin. D614G did not alter S protein synthesis, processing, or incorporation into SARS-CoV-2 particles, but D614G affinity for ACE2 was reduced due to a faster dissociation rate. Assessment of the S protein trimer by cryo-electron microscopy showed that D614G disrupts an interprotomer contact, and that the conformation is shifted towards an ACE2 binding-competent state, which is modeled to be on pathway for virion membrane fusion with target cells. Consistent with this more open conformation, neutralization potency of antibodies targeting the S protein receptor-binding domain was not attenuated.

DOI: 10.1016/j.cell.2020.09.032

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31229-0