8Y0Y

Cryo-EM structure of the 123-316 scDb/PT-RBD complex

Summary for 8Y0Y

• Entry DOI: 10.2210/pdb8y0y/pdb
• EMDB information: 38823
• Descriptor: 123-316 scDb, Spike glycoprotein, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: cryo-em, sars-cov2, antibody, rbd, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 137598.07

Authors

Jia, G.W.,Tong, Z.,Tong, J.Y.,Su, Z.M. (deposition date: 2024-01-23, release date: 2024-07-17, Last modification date: 2024-11-06)

Primary citation

Tong, Z.,Tong, J.,Lei, W.,Xie, Y.,Cui, Y.,Jia, G.,Li, S.,Zhang, Z.,Cheng, Z.,Xing, X.,Ma, H.,Deng, L.,Zhang, R.,Zhao, X.,Liu, K.,Wang, Q.,Qi, J.,Huang, H.,Song, R.,Su, Z.,Wu, G.,Lou, J.,Gao, G.F.
Deciphering a reliable synergistic bispecific strategy of rescuing antibodies for SARS-CoV-2 escape variants, including BA.2.86, EG.5.1, and JN.1.
Cell Rep, 43:114338-114338, 2024

PubMed Abstract: The game between therapeutic monoclonal antibodies (mAbs) and continuously emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has favored the virus, as most therapeutic mAbs have been evaded. Addressing this challenge, we systematically explored a reproducible bispecific antibody (bsAb)-dependent synergistic effect in this study. It could effectively restore the neutralizing activity of the bsAb when any of its single mAbs is escaped by variants. This synergy is primarily attributed to the binding angle of receptor-binding domain (RBD)-5, facilitating inter-spike cross-linking and promoting cryptic epitope exposure that classical antibody cocktails cannot achieve. Furthermore, RBD-5 with RBD-2, RBD-6, and RBD-7, alongside RBD-8, also exhibit significantly enhanced effects. This study not only shifts the paradigm in understanding antibody interactions but paves the way for developing more effective therapeutic antibodies against rapidly mutating SARS-CoV-2, with Dia-19 already showing promise against emerging variants like BA.2.86, EG.5.1, and JN.1.

PubMed: 38850530
DOI: 10.1016/j.celrep.2024.114338

Experimental method

ELECTRON MICROSCOPY (2.86 Å)