1区 · 综合性期刊
Article
作者: Wu, Kai ; Deng, Su-Jun ; Huang, Sijie ; Xia, Kaiwen ; Jiang, Yi ; Huang, Zifu ; Yin, Wanchao ; Liu, Peipei ; Xu, H. Eric ; Wang, Zongda ; Liu, Jia ; Song, Bin ; Gu, Chunyin ; Jia, Fangfang ; He, Xinheng ; Zheng, Jie ; Cheng, Xi ; Wu, Canrong ; Hu, Wen ; Xu, Peiyu ; Jiang, Hualiang ; Yuan, Qingning ; Xu, Youwei ; Wang, Xueping ; Wang, Xiaoxi ; Cao, Xiaodan
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has become the dominant infective strain. We report the structures of the Omicron spike trimer on its own and in complex with angiotensin-converting enzyme 2 (ACE2) or an anti-Omicron antibody. Most Omicron mutations are located on the surface of the spike protein and change binding epitopes to many current antibodies. In the ACE2-binding site, compensating mutations strengthen receptor binding domain (RBD) binding to ACE2. Both the RBD and the apo form of the Omicron spike trimer are thermodynamically unstable. An unusual RBD-RBD interaction in the ACE2-spike complex supports the open conformation and further reinforces ACE2 binding to the spike trimer. A broad-spectrum therapeutic antibody, JMB2002, which has completed a phase 1 clinical trial, maintains neutralizing activity against Omicron. JMB2002 binds to RBD differently from other characterized antibodies and inhibits ACE2 binding.