Evaluating the Synergistic Effects of Multi-Epitope Nanobodies on BA.2.86 Variant Immune Escape

IF 4.8 2区化学 Q2 CHEMISTRY, PHYSICAL

The Journal of Physical Chemistry Letters Pub Date : 2024-12-31 DOI:10.1021/acs.jpclett.4c03028

Jinxin Liu, Song Luo, Xiaole Xu, Enhao Zhang, Houde Liang, John Z. H. Zhang, Lili Duan

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Abstract

Addressing the frequent emergence of SARS-CoV-2 mutant strains requires therapeutic approaches with innovative neutralization mechanisms. The targeting of multivalent nanobodies can enhance potency and reduce the risk of viral escape, positioning them as promising drug candidates. Here, the synergistic mechanisms of the two types of nanobodies are investigated deeply. Our research revealed that the Fu2-1-Fu2-2 system exhibited significant synergy, whereas the Sb#15-Sb#68 system demonstrated antagonism, in which entropy was the dominant contributor to antagonism. Conformational analysis further demonstrated that the presence of a monomeric nanobody influenced the flexibility of residues near other epitopes, thereby affecting the overall synergy of the systems. Moreover, we identified that changes in the hydrogen bond network and the charge of residues played a critical role in the binding between nanobodies and spike. We hope this study will provide novel insights into the development of multivalent nanobody combinations.

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来源期刊

The Journal of Physical Chemistry Letters CHEMISTRY, PHYSICAL-NANOSCIENCE & NANOTECHNOLOGY

CiteScore

9.60

自引率

7.00%

发文量

1519

审稿时长

1.6 months

期刊介绍： The Journal of Physical Chemistry (JPC) Letters is devoted to reporting new and original experimental and theoretical basic research of interest to physical chemists, biophysical chemists, chemical physicists, physicists, material scientists, and engineers. An important criterion for acceptance is that the paper reports a significant scientific advance and/or physical insight such that rapid publication is essential. Two issues of JPC Letters are published each month.