Distinct Conformations of SARS-CoV-2 Omicron Spike Protein and Its Interaction with ACE2 and Antibody

Lee, Myeongsang; Major, Marian; Hong, Huixiao

doi:10.3390/ijms24043774

Distinct Conformations of SARS-CoV-2 Omicron Spike Protein and Its Interaction with ACE2 and Antibody

Journal Article · Tue Feb 14 00:00:00 EST 2023 · International Journal of Molecular Sciences (Online)

DOI:https://doi.org/10.3390/ijms24043774· OSTI ID:2471224

^[1]; Major, Marian ^[2]; ^[1]

US Food and Drug Administration (USFDA), Jefferson, AR (United States)
US Food and Drug Administration (USFDA), Silver Spring, MD (United States)

Since November 2021, Omicron has been the dominant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant that causes the coronavirus disease 2019 (COVID-19) and has continuously impacted human health. Omicron sublineages are still increasing and cause increased transmission and infection rates. The additional 15 mutations on the receptor binding domain (RBD) of Omicron spike proteins change the protein conformation, enabling the Omicron variant to evade neutralizing antibodies. For this reason, many efforts have been made to design new antigenic variants to induce effective antibodies in SARS-CoV-2 vaccine development. However, understanding the different states of Omicron spike proteins with and without external molecules has not yet been addressed. In this review, we analyze the structures of the spike protein in the presence and absence of angiotensin-converting enzyme 2 (ACE2) and antibodies. Compared to previously determined structures for the wildtype spike protein and other variants such as alpha, beta, delta, and gamma, the Omicron spike protein adopts a partially open form. The open-form spike protein with one RBD up is dominant, followed by the open-form spike protein with two RBD up, and the closed-form spike protein with the RBD down. It is suggested that the competition between antibodies and ACE2 induces interactions between adjacent RBDs of the spike protein, which lead to a partially open form of the Omicron spike protein. The comprehensive structural information of Omicron spike proteins could be helpful for the efficient design of vaccines against the Omicron variant.

View Accepted Manuscript (DOE)

Research Organization:: Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: SC0014664

OSTI ID:: 2471224

Journal Information:: International Journal of Molecular Sciences (Online), Journal Name: International Journal of Molecular Sciences (Online) Journal Issue: 4 Vol. 24; ISSN 1422-0067

Publisher:: MDPICopyright Statement

Country of Publication:: United States

Language:: English

References (62)

The transmission and diagnosis of 2019 novel coronavirus infection disease (COVID‐19): A Chinese perspective Han, Yu; Yang, Hailan Journal of Medical Virology, Vol. 92, Issue 6 https://doi.org/10.1002/jmv.25749	journal	March 2020
Omicron and Delta variant of SARS‐CoV‐2: A comparative computational study of spike protein Kumar, Suresh; Thambiraja, Thiviya S.; Karuppanan, Kalimuthu Journal of Medical Virology, Vol. 94, Issue 4 https://doi.org/10.1002/jmv.27526	journal	December 2021
Omicron (BA.1) and sub‐variants (BA.1.1, BA.2, and BA.3) of SARS‐CoV‐2 spike infectivity and pathogenicity: A comparative sequence and structural‐based computational assessment Kumar, Suresh; Karuppanan, Kalimuthu; Subramaniam, Gunasekaran Journal of Medical Virology, Vol. 94, Issue 10 https://doi.org/10.1002/jmv.27927	journal	June 2022
Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding Lu, Roujian; Zhao, Xiang; Li, Juan The Lancet, Vol. 395, Issue 10224 https://doi.org/10.1016/S0140-6736(20)30251-8	journal	February 2020
Biomechanical characterization of SARS-CoV-2 spike RBD and human ACE2 protein-protein interaction Cao, Wenpeng; Dong, Chuqiao; Kim, Seonghan Biophysical Journal, Vol. 120, Issue 6 https://doi.org/10.1016/j.bpj.2021.02.007	journal	March 2021
Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein Walls, Alexandra C.; Park, Young-Jun; Tortorici, M. Alejandra Cell, Vol. 181, Issue 2 https://doi.org/10.1016/j.cell.2020.02.058	journal	April 2020
Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2 Wang, Qihui; Zhang, Yanfang; Wu, Lili Cell, Vol. 181, Issue 4 https://doi.org/10.1016/j.cell.2020.03.045	journal	May 2020
Structural and functional characterizations of infectivity and immune evasion of SARS-CoV-2 Omicron Cui, Zhen; Liu, Pan; Wang, Nan Cell, Vol. 185, Issue 5 https://doi.org/10.1016/j.cell.2022.01.019	journal	March 2022
Broad neutralization of SARS-CoV-2 variants by an inhalable bispecific single-domain antibody Li, Cheng; Zhan, Wuqiang; Yang, Zhenlin Cell, Vol. 185, Issue 8 https://doi.org/10.1016/j.cell.2022.03.009	journal	April 2022
Structural and functional impact by SARS-CoV-2 Omicron spike mutations Zhang, Jun; Cai, Yongfei; Lavine, Christy L. Cell Reports, Vol. 39, Issue 4 https://doi.org/10.1016/j.celrep.2022.110729	journal	April 2022
Structures of Omicron spike complexes and implications for neutralizing antibody development Guo, Hangtian; Gao, Yan; Li, Tinghan Cell Reports, Vol. 39, Issue 5 https://doi.org/10.1016/j.celrep.2022.110770	journal	May 2022
Cryo-EM structures of SARS-CoV-2 Omicron BA.2 spike Stalls, Victoria; Lindenberger, Jared; Gobeil, Sophie M. -C. Cell Reports, Vol. 39, Issue 13 https://doi.org/10.1016/j.celrep.2022.111009	journal	June 2022
35B5 antibody potently neutralizes SARS-CoV-2 Omicron by disrupting the N-glycan switch via a conserved spike epitope Wang, Xiaofei; Chen, Xiangyu; Tan, Jiaxing Cell Host & Microbe, Vol. 30, Issue 6 https://doi.org/10.1016/j.chom.2022.03.035	journal	June 2022
Antibody evasion of SARS-CoV-2 Omicron BA.1, BA.1.1, BA.2, and BA.3 sub-lineages Ai, Jingwen; Wang, Xun; He, Xinyi Cell Host & Microbe, Vol. 30, Issue 8 https://doi.org/10.1016/j.chom.2022.05.001	journal	August 2022
Characterization of the enhanced infectivity and antibody evasion of Omicron BA.2.75 Cao, Yunlong; Song, Weiliang; Wang, Lei Cell Host & Microbe, Vol. 30, Issue 11 https://doi.org/10.1016/j.chom.2022.09.018	journal	November 2022
Structural and functional analysis of an inter-Spike bivalent neutralizing antibody against SARS-CoV-2 variants Li, Yaning; Fan, Qing; Zhou, Bing iScience, Vol. 25, Issue 6 https://doi.org/10.1016/j.isci.2022.104431	journal	June 2022
Structural diversity of the SARS-CoV-2 Omicron spike Gobeil, Sophie M. -C.; Henderson, Rory; Stalls, Victoria Molecular Cell, Vol. 82, Issue 11 https://doi.org/10.1016/j.molcel.2022.03.028	journal	June 2022
Conformational flexibility and structural variability of SARS-CoV2 S protein Pramanick, Ishika; Sengupta, Nayanika; Mishra, Suman Structure, Vol. 29, Issue 8 https://doi.org/10.1016/j.str.2021.04.006	journal	August 2021
Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC Raj, V. Stalin; Mou, Huihui; Smits, Saskia L. Nature, Vol. 495, Issue 7440 https://doi.org/10.1038/nature12005	journal	March 2013
Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19 Huang, Yuan; Yang, Chan; Xu, Xin-feng Acta Pharmacologica Sinica, Vol. 41, Issue 9 https://doi.org/10.1038/s41401-020-0485-4	journal	August 2020
The SARS-CoV-2 spike protein: balancing stability and infectivity Berger, Imre; Schaffitzel, Christiane Cell Research, Vol. 30, Issue 12 https://doi.org/10.1038/s41422-020-00430-4	journal	November 2020
Structural and biochemical mechanism for increased infectivity and immune evasion of Omicron BA.2 variant compared to BA.1 and their possible mouse origins Xu, Youwei; Wu, Canrong; Cao, Xiaodan Cell Research, Vol. 32, Issue 7 https://doi.org/10.1038/s41422-022-00672-4	journal	May 2022
A broadly neutralizing antibody against SARS-CoV-2 Omicron variant infection exhibiting a novel trimer dimer conformation in spike protein binding Wang, Yingdan; Zhan, Wuqiang; Liu, Jiangyan Cell Research, Vol. 32, Issue 9 https://doi.org/10.1038/s41422-022-00684-0	journal	June 2022
Neutralization against Omicron SARS-CoV-2 from previous non-Omicron infection Zou, Jing; Xia, Hongjie; Xie, Xuping Nature Communications, Vol. 13, Issue 1 https://doi.org/10.1038/s41467-022-28544-w	journal	February 2022
Cryo-EM structure of a SARS-CoV-2 omicron spike protein ectodomain Ye, Gang; Liu, Bin; Li, Fang Nature Communications, Vol. 13, Issue 1 https://doi.org/10.1038/s41467-022-28882-9	journal	March 2022
Neutralization of Omicron BA.1, BA.2, and BA.3 SARS-CoV-2 by 3 doses of BNT162b2 vaccine Kurhade, Chaitanya; Zou, Jing; Xia, Hongjie Nature Communications, Vol. 13, Issue 1 https://doi.org/10.1038/s41467-022-30681-1	journal	June 2022
Anatomy of Omicron BA.1 and BA.2 neutralizing antibodies in COVID-19 mRNA vaccinees Andreano, Emanuele; Paciello, Ida; Marchese, Silvia Nature Communications, Vol. 13, Issue 1 https://doi.org/10.1038/s41467-022-31115-8	journal	June 2022
Antibody affinity and cross-variant neutralization of SARS-CoV-2 Omicron BA.1, BA.2 and BA.3 following third mRNA vaccination Bellusci, Lorenza; Grubbs, Gabrielle; Zahra, Fatema Tuz Nature Communications, Vol. 13, Issue 1 https://doi.org/10.1038/s41467-022-32298-w	journal	August 2022
Omicron SARS-CoV-2 mutations stabilize spike up-RBD conformation and lead to a non-RBM-binding monoclonal antibody escape Zhao, Zhennan; Zhou, Jingya; Tian, Mingxiong Nature Communications, Vol. 13, Issue 1 https://doi.org/10.1038/s41467-022-32665-7	journal	August 2022
Patient-derived monoclonal antibody neutralizes SARS-CoV-2 Omicron variants and confers full protection in monkeys Fenwick, Craig; Turelli, Priscilla; Ni, Dongchun Nature Microbiology, Vol. 7, Issue 9 https://doi.org/10.1038/s41564-022-01198-6	journal	July 2022
A new coronavirus associated with human respiratory disease in China Wu, Fan; Zhao, Su; Yu, Bin Nature, Vol. 579, Issue 7798 https://doi.org/10.1038/s41586-020-2008-3	journal	February 2020
Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift Cameroni, Elisabetta; Bowen, John E.; Rosen, Laura E. Nature, Vol. 602, Issue 7898 https://doi.org/10.1038/s41586-021-04386-2	journal	December 2021
Memory B cell repertoire from triple vaccinees against diverse SARS-CoV-2 variants Wang, Kang; Jia, Zijing; Bao, Linilin Nature, Vol. 603, Issue 7903 https://doi.org/10.1038/s41586-022-04466-x	journal	January 2022
Molecular basis of receptor binding and antibody neutralization of Omicron Hong, Qin; Han, Wenyu; Li, Jiawei Nature, Vol. 604, Issue 7906 https://doi.org/10.1038/s41586-022-04581-9	journal	February 2022
BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection Cao, Yunlong; Yisimayi, Ayijiang; Jian, Fanchong Nature, Vol. 608, Issue 7923 https://doi.org/10.1038/s41586-022-04980-y	journal	June 2022
Serum neutralization of SARS-CoV-2 Omicron sublineages BA.1 and BA.2 in patients receiving monoclonal antibodies Bruel, Timothée; Hadjadj, Jérôme; Maes, Piet Nature Medicine, Vol. 28, Issue 6 https://doi.org/10.1038/s41591-022-01792-5	journal	March 2022
A thermostable, closed SARS-CoV-2 spike protein trimer Xiong, Xiaoli; Qu, Kun; Ciazynska, Katarzyna A. Nature Structural & Molecular Biology, Vol. 27, Issue 10 https://doi.org/10.1038/s41594-020-0478-5	journal	July 2020
Neutralization of the SARS-CoV-2 Omicron BA.1 and BA.2 Variants Yu, Jingyou; Collier, Ai-ris Y.; Rowe, Marjorie New England Journal of Medicine, Vol. 386, Issue 16 https://doi.org/10.1056/NEJMc2201849	journal	April 2022
Conformational transition of SARS-CoV-2 spike glycoprotein between its closed and open states Gur, Mert; Taka, Elhan; Yilmaz, Sema Zeynep The Journal of Chemical Physics, Vol. 153, Issue 7 https://doi.org/10.1063/5.0011141	journal	August 2020
Distant residues modulate conformational opening in SARS-CoV-2 spike protein Ray, Dhiman; Le, Ly; Andricioaei, Ioan Proceedings of the National Academy of Sciences, Vol. 118, Issue 43 https://doi.org/10.1073/pnas.2100943118	journal	October 2021
Mutational profile confers increased stability of SARS-CoV-2 spike protein in Brazilian isolates Santos, Felipe Rocha da Silva; de Azevedo, Marcela Santiago Pacheco; Bielavsky, Monica Journal of Biomolecular Structure and Dynamics, Vol. 40, Issue 23 https://doi.org/10.1080/07391102.2021.1982775	journal	October 2021
A human antibody of potent efficacy against SARS-CoV-2 in rhesus macaques showed strong blocking activity to B.1.351 Gu, Chunyin; Cao, Xiaodan; Wang, Zongda mAbs, Vol. 13, Issue 1 https://doi.org/10.1080/19420862.2021.1930636	journal	January 2021
The Protein Data Bank Berman, H. M. Nucleic Acids Research, Vol. 28, Issue 1 https://doi.org/10.1093/nar/28.1.235	journal	January 2000
The SARS-CoV-2 Spike variant D614G favors an open conformational state Mansbach, Rachael A.; Chakraborty, Srirupa; Nguyen, Kien Science Advances, Vol. 7, Issue 16 https://doi.org/10.1126/sciadv.abf3671	journal	April 2021
Structural insights for neutralization of Omicron variants BA.1, BA.2, BA.4, and BA.5 by a broadly neutralizing SARS-CoV-2 antibody Kumar, Sanjeev; Patel, Anamika; Lai, Lilin Science Advances, Vol. 8, Issue 40 https://doi.org/10.1126/sciadv.add2032	journal	October 2022
Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation Wrapp, Daniel; Wang, Nianshuang; Corbett, Kizzmekia S. Science, Vol. 367, Issue 6483 https://doi.org/10.1126/science.abb2507	journal	February 2020
Free fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein Toelzer, Christine; Gupta, Kapil; Yadav, Sathish K. N. Science, Vol. 370, Issue 6517 https://doi.org/10.1126/science.abd3255	journal	September 2020
Distinct conformational states of SARS-CoV-2 spike protein Cai, Yongfei; Zhang, Jun; Xiao, Tianshu Science https://doi.org/10.1126/science.abd4251	journal	July 2020
Ultrapotent antibodies against diverse and highly transmissible SARS-CoV-2 variants Wang, Lingshu; Zhou, Tongqing; Zhang, Yi Science, Vol. 373, Issue 6556 https://doi.org/10.1126/science.abh1766	journal	July 2021
SARS-CoV-2 Omicron variant: Antibody evasion and cryo-EM structure of spike protein–ACE2 complex Mannar, Dhiraj; Saville, James W.; Zhu, Xing Science, Vol. 375, Issue 6582 https://doi.org/10.1126/science.abn7760	journal	February 2022
Structural basis of SARS-CoV-2 Omicron immune evasion and receptor engagement McCallum, Matthew; Czudnochowski, Nadine; Rosen, Laura E. Science, Vol. 375, Issue 6583 https://doi.org/10.1126/science.abn8652	journal	February 2022
Structures of the Omicron spike trimer with ACE2 and an anti-Omicron antibody Yin, Wanchao; Xu, Youwei; Xu, Peiyu Science, Vol. 375, Issue 6584 https://doi.org/10.1126/science.abn8863	journal	March 2022
Structural basis for potent antibody neutralization of SARS-CoV-2 variants including B.1.1.529 Zhou, Tongqing; Wang, Lingshu; Misasi, John Science, Vol. 376, Issue 6591 https://doi.org/10.1126/science.abn8897	journal	April 2022
An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants of concern Du, Wenjuan; Hurdiss, Daniel L.; Drabek, Dubravka Science Immunology, Vol. 7, Issue 73 https://doi.org/10.1126/sciimmunol.abp9312	journal	July 2022
Structural Study of SARS-CoV-2 Antibodies Identifies a Broad-Spectrum Antibody That Neutralizes the Omicron Variant by Disassembling the Spike Trimer Zhan, Wuqiang; Tian, Xiaolong; Zhang, Xiang Journal of Virology, Vol. 96, Issue 16 https://doi.org/10.1128/jvi.00480-22	journal	August 2022
The SARS-CoV-2 Spike Variant D614G Favors an Open Conformational State Mansbach, Rachael; Chakraborty, Srirupa; Nguyen, Kien Los Alamos National Laboratory (LANL), Los Alamos, NM (United States) https://doi.org/10.25583/1760388	dataset	January 2021
A Review of SARS-CoV2: Compared With SARS-CoV and MERS-CoV Zhou, Huan; Yang, Junfa; Zhou, Chang Frontiers in Medicine, Vol. 8 https://doi.org/10.3389/fmed.2021.628370	journal	December 2021
The Future of the COVID-19 Pandemic: How Good (or Bad) Can the SARS-CoV2 Spike Protein Get? Nugent, Matthew A. Cells, Vol. 11, Issue 5 https://doi.org/10.3390/cells11050855	journal	March 2022
Anti-SARS-CoV-2 Antibodies Testing in Recipients of COVID-19 Vaccination: Why, When, and How? Lippi, Giuseppe; Henry, Brandon Michael; Plebani, Mario Diagnostics, Vol. 11, Issue 6 https://doi.org/10.3390/diagnostics11060941	journal	May 2021
Advanced Molecular and Immunological Diagnostic Methods to Detect SARS-CoV-2 Infection Rotondo, John Charles; Martini, Fernanda; Maritati, Martina Microorganisms, Vol. 10, Issue 6 https://doi.org/10.3390/microorganisms10061193	journal	June 2022
How Do Point Mutations Enhancing the Basic Character of the RBDs of SARS-CoV-2 Variants Affect Their Transmissibility and Infectivity Capacities? Barre, Annick; Klonjkowski, Bernard; Benoist, Hervé Viruses, Vol. 14, Issue 4 https://doi.org/10.3390/v14040783	journal	April 2022
Mutational profile confers increased stability of SARS-CoV-2 spike protein in Brazilian isolates da Silva Santos, Felipe Rocha; de Azevedo, Marcela Santiago Pacheco; Bielavsky, Monica Taylor & Francis https://doi.org/10.6084/m9.figshare.16785161.v1	dataset	January 2021

Similar Records

SARS-CoV-2 spike protein variant binding affinity to an angiotensin-converting enzyme 2 fusion glycoproteins

Journal Article · Mon Dec 05 19:00:00 EST 2022 · PLoS ONE · OSTI ID:2425791

Structural basis of SARS-CoV-2 Omicron immune evasion and receptor engagement

Journal Article · Mon Jan 24 19:00:00 EST 2022 · Science · OSTI ID:1891296

Effect of Delta and Omicron Mutations on the RBD-SD1 Domain of the Spike Protein in SARS-CoV-2 and the Omicron Mutations on RBD-ACE2 Interface Complex

Journal Article · Fri Sep 02 20:00:00 EDT 2022 · International Journal of Molecular Sciences (Online) · OSTI ID:1983118

Related Subjects

60 APPLIED LIFE SCIENCES
Omicron
SARS-CoV-2
angiotensin-converting enzyme 2
antibody
biochemistry & molecular biology
chemistry
open-form spike protein
receptor binding domain

Distinct Conformations of SARS-CoV-2 Omicron Spike Protein and Its Interaction with ACE2 and Antibody

Citation Formats

References (62)

Similar Records

Related Subjects