Single-Molecule Investigation of the Binding Interface Stability of SARS-CoV-2 Variants with ACE2

IF 4.8 Q2 NANOSCIENCE & NANOTECHNOLOGY

ACS Nanoscience Au Pub Date : 2024-03-08 DOI:10.1021/acsnanoscienceau.3c00060

Ankita Ray, Thu Thi Minh Tran, Rita dos Santos Natividade, Rodrigo A. Moreira, Joshua D. Simpson, Danahe Mohammed, Melanie Koehler, Simon J. L Petitjean, Qingrong Zhang, Fabrice Bureau, Laurent Gillet, Adolfo B. Poma* and David Alsteens*,

{"title":"Single-Molecule Investigation of the Binding Interface Stability of SARS-CoV-2 Variants with ACE2","authors":"Ankita Ray, Thu Thi Minh Tran, Rita dos Santos Natividade, Rodrigo A. Moreira, Joshua D. Simpson, Danahe Mohammed, Melanie Koehler, Simon J. L Petitjean, Qingrong Zhang, Fabrice Bureau, Laurent Gillet, Adolfo B. Poma* and David Alsteens*, ","doi":"10.1021/acsnanoscienceau.3c00060","DOIUrl":null,"url":null,"abstract":"<p >The SARS-CoV-2 pandemic spurred numerous research endeavors to comprehend the virus and mitigate its global severity. Understanding the binding interface between the virus and human receptors is pivotal to these efforts and paramount to curbing infection and transmission. Here we employ atomic force microscopy and steered molecular dynamics simulation to explore SARS-CoV-2 receptor binding domain (RBD) variants and angiotensin-converting enzyme 2 (ACE2), examining the impact of mutations at key residues upon binding affinity. Our results show that the Omicron and Delta variants possess strengthened binding affinity in comparison to the Mu variant. Further, using sera from individuals either vaccinated or with acquired immunity following Delta strain infection, we assess the impact of immunity upon variant RBD/ACE2 complex formation. Single-molecule force spectroscopy analysis suggests that vaccination before infection may provide stronger protection across variants. These results underscore the need to monitor antigenic changes in order to continue developing innovative and effective SARS-CoV-2 abrogation strategies.</p>","PeriodicalId":29799,"journal":{"name":"ACS Nanoscience Au","volume":"4 2","pages":"136–145"},"PeriodicalIF":4.8000,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acsnanoscienceau.3c00060","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Nanoscience Au","FirstCategoryId":"1085","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acsnanoscienceau.3c00060","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NANOSCIENCE & NANOTECHNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

The SARS-CoV-2 pandemic spurred numerous research endeavors to comprehend the virus and mitigate its global severity. Understanding the binding interface between the virus and human receptors is pivotal to these efforts and paramount to curbing infection and transmission. Here we employ atomic force microscopy and steered molecular dynamics simulation to explore SARS-CoV-2 receptor binding domain (RBD) variants and angiotensin-converting enzyme 2 (ACE2), examining the impact of mutations at key residues upon binding affinity. Our results show that the Omicron and Delta variants possess strengthened binding affinity in comparison to the Mu variant. Further, using sera from individuals either vaccinated or with acquired immunity following Delta strain infection, we assess the impact of immunity upon variant RBD/ACE2 complex formation. Single-molecule force spectroscopy analysis suggests that vaccination before infection may provide stronger protection across variants. These results underscore the need to monitor antigenic changes in order to continue developing innovative and effective SARS-CoV-2 abrogation strategies.

Abstract Image

查看原文本刊更多论文

SARS-CoV-2 变体与 ACE2 结合界面稳定性的单分子研究

SARS-CoV-2 大流行激发了大量研究工作，以了解这种病毒并减轻其在全球的严重性。了解病毒与人类受体之间的结合界面对这些工作至关重要，也是遏制感染和传播的关键。在这里，我们采用原子力显微镜和定向分子动力学模拟来探索 SARS-CoV-2 受体结合域 (RBD) 变体和血管紧张素转换酶 2 (ACE2)，研究关键残基的突变对结合亲和力的影响。我们的研究结果表明，与 Mu 变体相比，Omicron 和 Delta 变体具有更强的结合亲和力。此外，我们还利用接种过疫苗或感染 Delta 菌株后获得免疫力的个体的血清，评估了免疫力对变体 RBD/ACE2 复合物形成的影响。单分子力谱分析表明，在感染前接种疫苗可为不同变异株提供更强的保护。这些结果强调了监测抗原变化的必要性，以便继续开发创新和有效的 SARS-CoV-2 消减策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

ACS Nanoscience Au 材料科学、纳米科学-

CiteScore

4.20

自引率

0.00%

发文量

期刊介绍： ACS Nanoscience Au is an open access journal that publishes original fundamental and applied research on nanoscience and nanotechnology research at the interfaces of chemistry biology medicine materials science physics and engineering.The journal publishes short letters comprehensive articles reviews and perspectives on all aspects of nanoscience and nanotechnology:synthesis assembly characterization theory modeling and simulation of nanostructures nanomaterials and nanoscale devicesdesign fabrication and applications of organic inorganic polymer hybrid and biological nanostructuresexperimental and theoretical studies of nanoscale chemical physical and biological phenomenamethods and tools for nanoscience and nanotechnologyself- and directed-assemblyzero- one- and two-dimensional materialsnanostructures and nano-engineered devices with advanced performancenanobiotechnologynanomedicine and nanotoxicologyACS Nanoscience Au also publishes original experimental and theoretical research of an applied nature that integrates knowledge in the areas of materials engineering physics bioscience and chemistry into important applications of nanomaterials.