针对 SARS-CoV-2 变体受体结合域的嵌合肽抑制 ACE2 的相互作用。

IF 2.3 4区 医学 Q3 ALLERGY Asian Pacific journal of allergy and immunology Pub Date : 2024-11-17 DOI:10.12932/AP-030424-1833
Pisit Ubonsri, Jiraporn Panmanee, Ittipat Meewan, Promsin Masrinoul, Jukrapun Komaikul, Surapon Piboonpocanun
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引用次数: 0

摘要

背景:SARS-CoV-2 棘波(S)蛋白的受体结合域(RBD)在促进病毒进入方面起着关键作用,是疫苗开发和治疗的主要目标。尽管RBD经历了旨在逃避宿主免疫的突变,但其某些区域仍然保持不变:本研究旨在鉴定能够与不同变体中 RBD 的这些保守区域相互作用的多肽,并评估它们的中和潜力:方法:对 PhD-12 噬菌体展示文库进行筛选,以确定与 RBD 结合的噬菌体。筛选出的噬菌体克隆与多个变体的RBD结合,包括2019-nCoV、Delta(B.1.617.2)、Omicron(B.1.1.529)和XBB。对表达为嵌合构建体的多肽与 RBD、Omicron 三聚体 S、灭活的 SARS-CoV-2 病毒的结合以及中和活性进行了测试。使用分子对接法分析了结合位点:结果:两个被选中的噬菌体克隆显示了与多个变体的 RBD 结合的肽。嵌合肽(Trx-RB9 和 Trx-RB10)与灭活的 SARS-CoV-2 和 Omicron 三聚体 S 都有结合,半数最大有效浓度(EC50)分别为 111.9 和 360.2 nM。分子对接显示,在 Omicron 三聚体 S 的 RBD 中,Trx-RB9 和 Trx-RB10 有不同的结合位点。Trx-RB9 和 Trx-RB10 的混合物抑制了 78% 的重组人 ACE2 与 Omicron 三聚体 S 的结合:结论:嵌合的Trx-RB9和Trx-RB10肽能与SARS-CoV-2变体的RBD结合,并抑制ACE2与Omicron三聚体S的RBD结合。
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Chimeric peptides targeting the receptor-binding domain of SARS-CoV-2 variants inhibit ACE2 interaction.

Background: The receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein is pivotal in facilitating viral entry and serves as a major target for vaccine development and therapeutics. Despite undergoing mutations aimed at evading host immunity, certain regions within the RBD remain conserved.

Objective: This study aimed to identify peptides capable of interacting with these conserved regions of the RBD across various variants and assess their neutralization potential.

Methods: The PhD-12 phage display library underwent screening to identify phages binding to the RBD. Selected phage clones were examined for binding to the RBD of multiple variants, including 2019-nCoV, Delta (B.1.617.2), Omicron (B.1.1.529), and XBB. Peptides, expressed as chimeric constructs, were tested for their binding to the RBD, the Omicron trimeric S, inactivated SARS-CoV-2 virus, and neutralizing activity. The binding sites were analyzed using Molecular Docking.

Results: Two selected phage clones displayed peptides binding to the RBD of multiple variants. Chimeric T hioredoxin-peptides (Trx-RB9 and Trx-RB10) exhibited binding to both inactivated SARS-CoV-2 and the Omicron trimeric S, with half-maximum effective concentrations (EC50 ) values of 111.9 and 360.2 nM, respectively. Molecular docking revealed distinct binding sites within the RBD of the Omicron trimeric S for both Trx-RB9 and Trx-RB10. A mixture of Trx-RB9 and Trx-RB10 inhibited 78% of the binding of recombinant human ACE2 to the Omicron trimeric S.

Conclusions: The chimeric Trx-RB9 and Trx-RB10 peptides bind to the RBD of SARS-CoV-2 variants and inhibit the binding of ACE2 to the RBD of the Omicron trimeric S.

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来源期刊
CiteScore
12.80
自引率
0.00%
发文量
74
审稿时长
>12 weeks
期刊介绍: The Asian Pacific Journal of Allergy and Immunology (APJAI) is an online open access journal with the recent impact factor (2018) 1.747 APJAI published 4 times per annum (March, June, September, December). Four issues constitute one volume. APJAI publishes original research articles of basic science, clinical science and reviews on various aspects of allergy and immunology. This journal is an official journal of and published by the Allergy, Asthma and Immunology Association, Thailand. The scopes include mechanism, pathogenesis, host-pathogen interaction, host-environment interaction, allergic diseases, immune-mediated diseases, epidemiology, diagnosis, treatment and prevention, immunotherapy, and vaccine. All papers are published in English and are refereed to international standards.
期刊最新文献
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