9SAT

Monoclonal Antibodies from COVID-19 Convalescent Patients Target Cryptic Epitopes for Universal SARS-CoV-2 Neutralization

Summary for 9SAT

• Entry DOI: 10.2210/pdb9sat/pdb
• Descriptor: TAU-1109 Fab Heavy Chain, TAU-1109 Fab Light Chain, Spike protein S1, ... (5 entities in total)
• Functional Keywords: immune complex, sars-cov-2, receptor binding domain, neutralizing antibody, viral protein
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 77366.39

Authors

Dessau, M.,Harit, A. (deposition date: 2025-08-07, release date: 2026-03-18, Last modification date: 2026-04-01)

Primary citation

Harit, A.,Mor, M.,Yefet, R.,Izhaki-Tavor, L.S.,Gal-Tanamy, M.,Freund, N.T.,Dessau, M.
Monoclonal antibodies from COVID-19 convalescent patients target cryptic epitopes for broad SARS-CoV-2 neutralization.
Proc.Natl.Acad.Sci.USA, 123:e2523864123-e2523864123, 2026

PubMed Abstract: The COVID-19 pandemic, which has resulted in over seven million global fatalities, poses a substantial threat to public health and precipitated a global economic crisis. Emerging variants of concern (VOCs) with enhanced transmissibility and improved immune evasion may compromise the efficacy of current antiviral and immunotherapies, necessitating comprehensive investigations into the immune response to SARS-CoV-2. The conformational dynamics of the receptor binding domain in SARS-CoV-2 spike and the presentation of neutralizing antibody epitopes influence viral transmission and infection rates. In this study, we have identified highly conserved non-receptor-binding motif epitopes for two potent monoclonal antibodies (mAbs), TAU-1109 and TAU-2310, isolated from convalescent human patients, which contribute to the broad neutralizing activity of these mAbs against all the circulating VOCs, including the recently emerged Omicron subvariants. We employed high-resolution structural data in conjunction with systematic biochemical investigation to elucidate the neutralization mechanism of TAU-1109 and TAU-2310. The mechanism involves antibody-mediated destabilization of the spike trimer, resulting in the premature shedding of the S1 subunit and rendering the spike incapable of mediating host cell entry. The identification of conserved cryptic epitopes in our study advances the mechanistic understanding of immune response against SARS-CoV-2, providing alternative avenues for the development of universal therapeutic antibodies and vaccines to combat COVID-19.

PubMed: 41880581
DOI: 10.1073/pnas.2523864123

Experimental method

X-RAY DIFFRACTION (2.56 Å)