7U0Q

SARS-Cov2 S protein structure in complex with neutralizing monoclonal antibody 002-02

This is a non-PDB format compatible entry.

Summary for 7U0Q

• Entry DOI: 10.2210/pdb7u0q/pdb
• EMDB information: 26263
• Descriptor: Spike glycoprotein, mAb 002-02 light chain, mAb 002-02 Heavy chain, ... (6 entities in total)
• Functional Keywords: sars-cov2 6p spike protein, immune complex, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); More
• Total number of polymer chains: 7
• Total formula weight: 558038.08

Authors

Patel, A.,Ortlund, E. (deposition date: 2022-02-18, release date: 2023-03-01, Last modification date: 2024-10-23)

Primary citation

Patel, A.,Kumar, S.,Lai, L.,Chakravarthy, C.,Valanparambil, R.,Reddy, E.S.,Gottimukkala, K.,Bajpai, P.,Raju, D.R.,Edara, V.V.,Davis-Gardner, M.E.,Linderman, S.,Dixit, K.,Sharma, P.,Mantus, G.,Cheedarla, N.,Verkerke, H.P.,Frank, F.,Neish, A.S.,Roback, J.D.,Davis, C.W.,Wrammert, J.,Ahmed, R.,Suthar, M.S.,Sharma, A.,Murali-Krishna, K.,Chandele, A.,Ortlund, E.A.
Molecular basis of SARS-CoV-2 Omicron variant evasion from shared neutralizing antibody response.
Structure, 31:801-811.e5, 2023

PubMed Abstract: Understanding the molecular features of neutralizing epitopes is important for developing vaccines/therapeutics against emerging SARS-CoV-2 variants. We describe three monoclonal antibodies (mAbs) generated from COVID-19 recovered individuals during the first wave of the pandemic in India. These mAbs had publicly shared near germline gene usage and potently neutralized Alpha and Delta, poorly neutralized Beta, and failed to neutralize Omicron BA.1 SARS-CoV-2 variants. Structural analysis of these mAbs in complex with trimeric spike protein showed that all three mAbs bivalently bind spike with two mAbs targeting class 1 and one targeting a class 4 receptor binding domain epitope. The immunogenetic makeup, structure, and function of these mAbs revealed specific molecular interactions associated with the potent multi-variant binding/neutralization efficacy. This knowledge shows how mutational combinations can affect the binding or neutralization of an antibody, which in turn relates to the efficacy of immune responses to emerging SARS-CoV-2 escape variants.

PubMed: 37167972
DOI: 10.1016/j.str.2023.04.010

Experimental method

ELECTRON MICROSCOPY (3.86 Å)