8XI6

SARS-CoV-2 Omicron BQ.1.1 Variant Spike Protein Complexed with MO11 Fab

Summary for 8XI6

• Entry DOI: 10.2210/pdb8xi6/pdb
• EMDB information: 38372
• Descriptor: Spike glycoprotein, MO11 heavy chain, MO11 light chain, ... (7 entities in total)
• Functional Keywords: sars-cov-2, antibody complex, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 9
• Total formula weight: 570709.98

Authors

Ishimaru, H.,Nishimura, M.,Shigematsu, H.,Marini, M.I.,Hasegawa, N.,Takamiya, R.,Iwata, S.,Mori, Y. (deposition date: 2023-12-19, release date: 2024-04-24, Last modification date: 2024-10-16)

Primary citation

Ishimaru, H.,Nishimura, M.,Shigematsu, H.,Marini, M.I.,Hasegawa, N.,Takamiya, R.,Iwata, S.,Mori, Y.
Epitopes of an antibody that neutralizes a wide range of SARS-CoV-2 variants in a conserved subdomain 1 of the spike protein.
J.Virol., 98:e0041624-e0041624, 2024

PubMed Abstract: The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued, enabling the virus to escape from host immunity by changing its spike antigen, while biased toward the receptor-binding domain and N-terminal domain. Here, we isolated a novel pan-SARS-CoV-2 neutralizing antibody (which we named MO11) for even the recent dominators XBB.1.16 and EG.5.1, from a convalescent patient who had received three doses of an original mRNA COVID-19 vaccination. A cryo-electron microscopy analysis of the spike-MO11 complex at 2.3 Å atomic resolution revealed that it recognizes a conserved epitope hidden behind a glycan shield at N331 on subdomain 1 (SD1), holding both the N- and C-terminal segments comprising SD1. Our identification of MO11 unveiled the functional importance of SD1 for the spike's function, and we discuss the potential availability of a novel common epitope among the SARS-CoV-2 variants.IMPORTANCENovel severe acute respiratory syndrome coronavirus 2 variants with immune evasion ability are still repeatedly emerging, nonetheless, a part of immunity developed in responding to the antigen of earlier variants retains efficacy against recent variants irrespective of the numerous mutations. In exploration for the broadly effective antibodies, we identified a cross-neutralizing antibody, named MO11, from the B cells of the convalescent patient. MO11 targets a novel epitope in subdomain 1 (SD1) and was effective against all emerging variants including XBB.1.16 and EG.5.1. The neutralizing activity covering from D614G to EG.5.1 variants was explained by the conservation of the epitope, and it revealed the importance of the subdomain on regulating the function of the antigen for viral infection. Demonstrated identification of the neutralizing antibody that recognizes a conserved epitope implies basal contribution of such group of antibodies for prophylaxis against COVID-19.

PubMed: 38624232
DOI: 10.1128/jvi.00416-24

Experimental method

ELECTRON MICROSCOPY (2.3 Å)