Structural and functional impact by SARS-CoV-2 Omicron spike mutations

被引:99
作者
Zhang, Jun [1 ,2 ]
Cai, Yongfei [1 ,2 ]
Lavine, Christy L. [3 ]
Peng, Hanqin [1 ]
Zhu, Haisun [4 ]
Anand, Krishna [4 ]
Tong, Pei [5 ,10 ]
Gautam, Avneesh [5 ,10 ]
Mayer, Megan L. [6 ,7 ]
Rits-Volloch, Sophia [1 ]
Wang, Shaowei [8 ]
Sliz, Piotr [1 ,2 ]
Wesemann, Duane R. [5 ,10 ]
Yang, Wei [4 ,11 ]
Seaman, Michael S. [3 ]
Lu, Jianming [8 ,9 ]
Xiao, Tianshu [1 ,2 ]
Chen, Bing [1 ,2 ]
机构
[1] Boston Childrens Hosp, Div Mol Med, 3 Blackfan St, Boston, MA 02115 USA
[2] Harvard Med Sch, Dept Pediat, 3 Blackfan St, Boston, MA 02115 USA
[3] Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, 330 Brookline Ave, Boston, MA 02215 USA
[4] Harvard Inst Med, Inst Prot Innovat, 4 Blackfan Circle, Boston, MA 02115 USA
[5] Brigham & Womens Hosp, Dept Med, Div Allergy & Clin Immunol, Boston, MA 02115 USA
[6] Harvard CryoEM Ctr Struct Biol, 250 Longwood Ave, Boston, MA 02115 USA
[7] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, 240 Longwood Ave, Boston, MA 02115 USA
[8] Codex BioSolut Inc, 12358 Parklawn Dr, Rockville, MD 20852 USA
[9] Georgetown Univ, Dept Biochem & Mol & Cellular Biol, Sch Med, 3900 Reservoir Rd NW, Washington, DC 20057 USA
[10] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA
[11] GV20 Therapeut LLC, 1 Broadway Floor 14, Cambridge, MA 02142 USA
来源
CELL REPORTS | 2022年 / 39卷 / 04期
关键词
CRYO-EM STRUCTURE; CELL ENTRY; CORONAVIRUS;
D O I
10.1016/j.celrep.2022.110729
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), bearing an unusually high number of mutations, has become a dominant strain in many countries within several weeks. We report here structural, functional, and antigenic properties of its full-length spike (S) protein with a native sequence in comparison with those of previously prevalent variants. Omicron S requires a substantially higher level of host receptor ACE2 for efficient membrane fusion than other variants, possibly explaining its unexpected cellular tropism. Mutations not only remodel the antigenic structure of the N-terminal domain of the S protein but also alter the surface of the receptor-binding domain in a way not seen in other variants, consistent with its remarkable resistance to neutralizing antibodies. These results suggest that Omicron Shas acquired an extraordinary ability to evade host immunity by excessive mutations, which also compromise its fusogenic capability.
引用
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页数:16
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