Amyloidogenesis of SARS-CoV-2 delta plus and omicron variants receptor-binding domain (RBD): impact of SUMO fusion tag.

IF 2 4区生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology Letters Pub Date : 2024-08-25 DOI:10.1007/s10529-024-03525-9

Sadegh Zargan, Hasan Jalili, Bahareh Dabirmanesh, Saba Mesdaghinia, Khosro Khajeh

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Abstract

Purpose: The RBD of SARS-CoV-2 mediates viral entry into host cells by binding to the host receptor ACE2. SARS-CoV-2 infection is linked to various health issues resembling amyloid-related problems, persuading us to investigate the amyloidogenicity of the SARS-CoV-2 spike RBD.

Methods: The FoldAmyloid program was used to assess the amyloidogenic propensities in the RBD of Delta Plus and RBD of the Omicron variant, with and without the SUMO tag. After the expression of RBDs, purification, and dialysis steps were performed, subsequently the ThT assay, FTIR, and TEM were employed to check the RBD ability to form fibrils.

Results: The ThT assay, TEM, and FTIR revealed the ability of RBD to self-assemble into β-sheet-rich aggregates (48.4% β-sheet content). Additionally, the presence of the SUMO tag reduced the formation of RBD amyloid-like fibrils. The amyloidogenic potential of Omicron RBD was higher than Delta Plus, according to both in silico and experimental analyses.

Conclusions: The SARS-CoV-2 RBD can assemble itself by forming aggregates containing amyloid-like fibrils and the presence of a SUMO tag can significantly decrease the formation of RBD amyloid-like fibrils. In silico analysis suggested that variation in the ThT fluorescence intensity of amyloid accumulations in the two SARS-CoV-2 strains arises from specific mutations in their RBD regions.

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SARS-CoV-2 delta plus 和 omicron 变体受体结合域 (RBD) 的淀粉样蛋白生成：SUMO 融合标签的影响。

目的：SARS-CoV-2 的 RBD 通过与宿主受体 ACE2 结合介导病毒进入宿主细胞。SARS-CoV-2感染与各种类似淀粉样蛋白相关问题的健康问题有关，这促使我们研究SARS-CoV-2尖峰RBD的淀粉样蛋白致病性：方法：我们使用 FoldAmyloid 程序评估了带和不带 SUMO 标记的 Delta Plus RBD 和 Omicron 变体 RBD 的淀粉样蛋白生成倾向。在表达 RBD 后，进行了纯化和透析步骤，随后采用 ThT 检测、傅立叶变换红外光谱和 TEM 检测 RBD 形成纤维的能力：结果：ThT测定、TEM和傅立叶变换红外光谱显示，RBD能够自组装成富含β片的聚集体（β片含量为48.4%）。此外，SUMO 标记的存在减少了 RBD 淀粉样纤维的形成。根据硅学和实验分析，Omicron RBD的淀粉样蛋白生成潜力高于Delta Plus：结论：SARS-CoV-2 RBD可通过形成含有淀粉样纤维的聚集体来组装自身，而SUMO标签的存在可显著减少RBD淀粉样纤维的形成。硅学分析表明，两株SARS-CoV-2淀粉样蛋白聚集体的ThT荧光强度差异是由其RBD区域的特定突变引起的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biotechnology Letters 工程技术-生物工程与应用微生物

CiteScore

5.90

自引率

3.70%

发文量

108

审稿时长

1.2 months

期刊介绍： Biotechnology Letters is the world’s leading rapid-publication primary journal dedicated to biotechnology as a whole – that is to topics relating to actual or potential applications of biological reactions affected by microbial, plant or animal cells and biocatalysts derived from them. All relevant aspects of molecular biology, genetics and cell biochemistry, of process and reactor design, of pre- and post-treatment steps, and of manufacturing or service operations are therefore included. Contributions from industrial and academic laboratories are equally welcome. We also welcome contributions covering biotechnological aspects of regenerative medicine and biomaterials and also cancer biotechnology. Criteria for the acceptance of papers relate to our aim of publishing useful and informative results that will be of value to other workers in related fields. The emphasis is very much on novelty and immediacy in order to justify rapid publication of authors’ results. It should be noted, however, that we do not normally publish papers (but this is not absolute) that deal with unidentified consortia of microorganisms (e.g. as in activated sludge) as these results may not be easily reproducible in other laboratories. Papers describing the isolation and identification of microorganisms are not regarded as appropriate but such information can be appended as supporting information to a paper. Papers dealing with simple process development are usually considered to lack sufficient novelty or interest to warrant publication.