tetano
Editor, Senior Moderator
Cell Rep
. 2022 Apr 11;110729.
doi: 10.1016/j.celrep.2022.110729. Online ahead of print.
Structural and functional impact by SARS-CoV-2 Omicron spike mutations
Jun Zhang[SUP] 1 [/SUP], Yongfei Cai[SUP] 1 [/SUP], Christy L Lavine[SUP] 2 [/SUP], Hanqin Peng[SUP] 3 [/SUP], Haisun Zhu[SUP] 4 [/SUP], Krishna Anand[SUP] 4 [/SUP], Pei Tong[SUP] 5 [/SUP], Avneesh Gautam[SUP] 5 [/SUP], Megan L Mayer[SUP] 6 [/SUP], Sophia Rits-Volloch[SUP] 3 [/SUP], Shaowei Wang[SUP] 7 [/SUP], Piotr Sliz[SUP] 1 [/SUP], Duane R Wesemann[SUP] 5 [/SUP], Wei Yang[SUP] 4 [/SUP], Michael S Seaman[SUP] 2 [/SUP], Jianming Lu[SUP] 8 [/SUP], Tianshu Xiao[SUP] 9 [/SUP], Bing Chen[SUP] 10 [/SUP]
Affiliations
Abstract
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 S has acquired an extraordinary ability to evade host immunity by excessive mutations, which also compromise its fusogenic capability.
Keywords: CP: Molecular biology; SARS-CoV-2; cryo-EM; spike protein; structure.
. 2022 Apr 11;110729.
doi: 10.1016/j.celrep.2022.110729. Online ahead of print.
Structural and functional impact by SARS-CoV-2 Omicron spike mutations
Jun Zhang[SUP] 1 [/SUP], Yongfei Cai[SUP] 1 [/SUP], Christy L Lavine[SUP] 2 [/SUP], Hanqin Peng[SUP] 3 [/SUP], Haisun Zhu[SUP] 4 [/SUP], Krishna Anand[SUP] 4 [/SUP], Pei Tong[SUP] 5 [/SUP], Avneesh Gautam[SUP] 5 [/SUP], Megan L Mayer[SUP] 6 [/SUP], Sophia Rits-Volloch[SUP] 3 [/SUP], Shaowei Wang[SUP] 7 [/SUP], Piotr Sliz[SUP] 1 [/SUP], Duane R Wesemann[SUP] 5 [/SUP], Wei Yang[SUP] 4 [/SUP], Michael S Seaman[SUP] 2 [/SUP], Jianming Lu[SUP] 8 [/SUP], Tianshu Xiao[SUP] 9 [/SUP], Bing Chen[SUP] 10 [/SUP]
Affiliations
- PMID: 35452593
- PMCID: PMC8995406
- DOI: 10.1016/j.celrep.2022.110729
Abstract
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 S has acquired an extraordinary ability to evade host immunity by excessive mutations, which also compromise its fusogenic capability.
Keywords: CP: Molecular biology; SARS-CoV-2; cryo-EM; spike protein; structure.