Epimaps of the SARS-CoV-2 Receptor-Binding Domain Mutational Landscape: Insights into Protein Stability, Epitope Prediction, and Antibody Binding DOI Creative Commons
Eleni Pitsillou, Assam El‐Osta, Andrew Hung

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 301 - 301

Published: Feb. 18, 2025

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses an ongoing threat to the efficacy vaccines and therapeutic antibodies. Mutations predominantly affect receptor-binding domain (RBD) spike protein, which mediates viral entry. RBD is also a major target monoclonal antibodies that were authorised for use during pandemic. In this study, in silico approach was used investigate mutational landscape SARS-CoV-2 variants, including currently circulating Omicron subvariants. A total 40 single-point mutations assessed their potential effect on protein stability dynamics. Destabilising effects predicted such as L455S F456L, while stabilising R346T. Conformational B-cell epitope predictions subsequently performed wild-type (WT) variant RBDs. from located within residues regions found correspond sites targeted by Furthermore, homology models generated utilised protein-antibody docking. binding characteristics 10 against WT 14 evaluated. Through evaluating affinities, interactions, energy contributions residues, contributing evasion identified. findings study provide insight into structural molecular mechanisms underlying neutralising antibody evasion. Future development could focus broadly antibodies, engineering with enhanced affinity, targeting beyond RBD.

Language: Английский

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 DOI Creative Commons
Zhou Tong, Jianyu Tong, Wenwen Lei

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(6), P. 114338 - 114338

Published: June 1, 2024

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

Language: Английский

Citations

4
Design of SARS-CoV-2 RBD Immunogens to Focus Immune Responses Towards Conserved Coronavirus Epitopes DOI Open Access
Caitlin Harris, A. Brenda Kapingidza,

James Emmanuel San

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

SARS-CoV-2 continues to evolve, with new variants emerging that evade pre-existing immunity and limit the efficacy of existing vaccines. One approach towards developing superior, variant-proof vaccines is engineer immunogens preferentially elicit antibodies broad cross-reactivity against its by targeting conserved epitopes on spike. The inner outer faces Receptor Binding Domain (RBD) are two such regions targeted recognize diverse human animal coronaviruses. To promote elicitation vaccination, we engineered "resurfaced" RBD contained mutations at exposed residues outside target epitopes. In context immunity, these vaccine candidates aim disfavor strain-specific immunodominant Motif (RBM) while boosting induction face antibodies. resurfaced were stable, lacked binding monoclonal limited breadth, maintained strong interactions broadly neutralizing When used as vaccines, they humoral responses RBM intended. Multimerization nanoparticles further increased immunogenicity RBDs immunogens, thus supporting resurfacing a promising immunogen design rationally shift natural immune develop more protective

Language: Английский

Citations

0
A type of cryptic epitope-binding antibody on SARS-CoV-2 RBD retains the neutralization against SARS-CoV-2 variants and sarbecoviruses DOI
Weiwei Zou,

Zeshuai Zhang,

Xinyong Liu

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 140046 - 140046

Published: Jan. 1, 2025

Language: Английский

Citations

0
Immune evasion of Omicron variants JN.1, KP.2, and KP.3 to the polyclonal and monoclonal antibodies from COVID-19 convalescents and vaccine recipients DOI
Qian Wu,

Hairuo Wu,

Yabin Hu

et al.

Antiviral Research, Journal Year: 2025, Volume and Issue: unknown, P. 106092 - 106092

Published: Jan. 1, 2025

Language: Английский

Citations

0
Epimaps of the SARS-CoV-2 Receptor-Binding Domain Mutational Landscape: Insights into Protein Stability, Epitope Prediction, and Antibody Binding DOI Creative Commons
Eleni Pitsillou, Assam El‐Osta, Andrew Hung

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 301 - 301

Published: Feb. 18, 2025

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses an ongoing threat to the efficacy vaccines and therapeutic antibodies. Mutations predominantly affect receptor-binding domain (RBD) spike protein, which mediates viral entry. RBD is also a major target monoclonal antibodies that were authorised for use during pandemic. In this study, in silico approach was used investigate mutational landscape SARS-CoV-2 variants, including currently circulating Omicron subvariants. A total 40 single-point mutations assessed their potential effect on protein stability dynamics. Destabilising effects predicted such as L455S F456L, while stabilising R346T. Conformational B-cell epitope predictions subsequently performed wild-type (WT) variant RBDs. from located within residues regions found correspond sites targeted by Furthermore, homology models generated utilised protein-antibody docking. binding characteristics 10 against WT 14 evaluated. Through evaluating affinities, interactions, energy contributions residues, contributing evasion identified. findings study provide insight into structural molecular mechanisms underlying neutralising antibody evasion. Future development could focus broadly antibodies, engineering with enhanced affinity, targeting beyond RBD.

Language: Английский

Citations

0