EMD-38618

Single-particle
2.16 Å
EMD-38618 Deposition: 09/01/2024
Map released: 17/07/2024
Last modified: 23/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-38618

SARS-CoV-2 RBD + IMCAS-364 + hACE2

EMD-38618

Single-particle
2.16 Å
EMD-38618 Deposition: 09/01/2024
Map released: 17/07/2024
Last modified: 23/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens, Severe acute respiratory syndrome coronavirus 2
Sample: Cryo-EM structure of SARS-CoV-2 RBD + IMCAS-364 + hACE2 (Global Refinement)
Fitted models: 8xsf (Avg. Q-score: 0.416)

Deposition Authors: Tong Z, Cui Y, Xie Y, Tong J, Gao GF, Qi J
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.
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 GF
(2024) Cell Rep , 43 , 114338 - 114338
PUBMED: 38850530
DOI: doi:10.1016/j.celrep.2024.114338
ISSN: 2211-1247
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.