7UPL

SARS-Cov2 Omicron varient S protein structure in complex with neutralizing monoclonal antibody 002-S21F2

Summary for 7UPL

• Entry DOI: 10.2210/pdb7upl/pdb
• EMDB information: 26669
• Descriptor: Spike glycoprotein, mAB 002-S21F2 light chain, mAb 002-S21F2 heavy chain, ... (5 entities in total)
• Functional Keywords: sars-cov2, 6p, spike protein, immune complex, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); More
• Total number of polymer chains: 7
• Total formula weight: 573412.73

Authors

Patel, A.,Ortlund, E. (deposition date: 2022-04-15, release date: 2022-08-10, Last modification date: 2024-10-09)

Primary citation

Kumar, S.,Patel, A.,Lai, L.,Chakravarthy, C.,Valanparambil, R.,Reddy, E.S.,Gottimukkala, K.,Davis-Gardner, M.E.,Edara, V.V.,Linderman, S.,Nayak, K.,Dixit, K.,Sharma, P.,Bajpai, P.,Singh, V.,Frank, F.,Cheedarla, N.,Verkerke, H.P.,Neish, A.S.,Roback, J.D.,Mantus, G.,Goel, P.K.,Rahi, M.,Davis, C.W.,Wrammert, J.,Godbole, S.,Henry, A.R.,Douek, D.C.,Suthar, M.S.,Ahmed, R.,Ortlund, E.,Sharma, A.,Murali-Krishna, K.,Chandele, A.
Structural insights for neutralization of Omicron variants BA.1, BA.2, BA.4, and BA.5 by a broadly neutralizing SARS-CoV-2 antibody.
Sci Adv, 8:eadd2032-eadd2032, 2022

PubMed Abstract: In this study, by characterizing several human monoclonal antibodies (mAbs) isolated from single B cells of the COVID-19-recovered individuals in India who experienced ancestral Wuhan strain (WA.1) of SARS-CoV-2 during early stages of the pandemic, we found a receptor binding domain (RBD)-specific mAb 002-S21F2 that has rare gene usage and potently neutralized live viral isolates of SARS-CoV-2 variants including Alpha, Beta, Gamma, Delta, and Omicron sublineages (BA.1, BA.2, BA.2.12.1, BA.4, and BA.5) with IC ranging from 0.02 to 0.13 μg/ml. Structural studies of 002-S21F2 in complex with spike trimers of Omicron and WA.1 showed that it targets a conformationally conserved epitope on the outer face of RBD (class 3 surface) outside the ACE2-binding motif, thereby providing a mechanistic insights for its broad neutralization activity. The discovery of 002-S21F2 and the broadly neutralizing epitope it targets have timely implications for developing a broad range of therapeutic and vaccine interventions against SARS-CoV-2 variants including Omicron sublineages.

PubMed: 36197988
DOI: 10.1126/sciadv.add2032

Experimental method

ELECTRON MICROSCOPY (4.1 Å)