8SWH

Local refinement of SARS-CoV-2 (HP-GSAS-Mut7) spike NTD in complex with TXG-0078 Fab

Summary for 8SWH

• Entry DOI: 10.2210/pdb8swh/pdb
• EMDB information: 40814
• Descriptor: Spike glycoprotein, TXG-0078 Fab Heavy chain, TXG-0078 Fab Light chain, ... (5 entities in total)
• Functional Keywords: sars-cov-2, spike, covid, monoclonal antibody, complex, ntd, 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: 3
• Total formula weight: 172957.73

Authors

Bangaru, B.,Ward, A. (deposition date: 2023-05-18, release date: 2024-05-22, Last modification date: 2024-11-13)

Primary citation

Hurtado, J.,Rogers, T.F.,Jaffe, D.B.,Adams, B.A.,Bangaru, S.,Garcia, E.,Capozzola, T.,Messmer, T.,Sharma, P.,Song, G.,Beutler, N.,He, W.,Dueker, K.,Musharrafieh, R.,Burbach, S.,Truong, A.,Stubbington, M.J.T.,Burton, D.R.,Andrabi, R.,Ward, A.B.,McDonnell, W.J.,Briney, B.
Deep repertoire mining uncovers ultra-broad coronavirus neutralizing antibodies targeting multiple spike epitopes.
Cell Rep, 43:114307-114307, 2024

PubMed Abstract: The development of vaccines and therapeutics that are broadly effective against known and emergent coronaviruses is an urgent priority. We screened the circulating B cell repertoires of COVID-19 survivors and vaccinees to isolate over 9,000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific monoclonal antibodies (mAbs), providing an expansive view of the SARS-CoV-2-specific Ab repertoire. Among the recovered antibodies was TXG-0078, an N-terminal domain (NTD)-specific neutralizing mAb that recognizes diverse alpha- and beta-coronaviruses. TXG-0078 achieves its exceptional binding breadth while utilizing the same VH1-24 variable gene signature and heavy-chain-dominant binding pattern seen in other NTD-supersite-specific neutralizing Abs with much narrower specificity. We also report CC24.2, a pan-sarbecovirus neutralizing antibody that targets a unique receptor-binding domain (RBD) epitope and shows similar neutralization potency against all tested SARS-CoV-2 variants, including BQ.1.1 and XBB.1.5. A cocktail of TXG-0078 and CC24.2 shows protection in vivo, suggesting their potential use in variant-resistant therapeutic Ab cocktails and as templates for pan-coronavirus vaccine design.

PubMed: 38848216
DOI: 10.1016/j.celrep.2024.114307

Experimental method

ELECTRON MICROSCOPY (3.88 Å)