分子模拟在 SARS-CoV-2 与人体相互作用组中引发心血管疾病的作用:对 ImitateDB 的更新。

Role of molecular mimicry in the SARS-CoV-2-human interactome for pathogenesis of cardiovascular diseases: An update to ImitateDB.

机构信息

Computational and Structural Biology Laboratory, Department of Biological Sciences and Engineering, Netaji Subhas University of Technology, Dwarka, New Delhi 110078, India.

Computational and Structural Biology Laboratory, Department of Biological Sciences and Engineering, Netaji Subhas University of Technology, Dwarka, New Delhi 110078, India.

出版信息

Comput Biol Chem. 2023 Oct;106:107919. doi: 10.1016/j.compbiolchem.2023.107919. Epub 2023 Jul 7.

Abstract

Mimicry of host proteins is a strategy employed by pathogens to hijack host functions. Domain and motif mimicry was explored in the experimental and predicted SARS-CoV-2-human interactome. The host first interactor proteins were also added to capture the continuum of the interactions. The domains and motifs of the proteins were annotated using NCBI CD Search and ScanProsite, respectively. Host and pathogen proteins with a common host interactor and similar domain/motif constitute a mimicry pair indicating global structural similarity (domain mimicry pair; DMP) or local sequence similarity (motif mimicry pair; MMP). 593 DMPs and 7,02,472 MMPs were determined. AAA, DEXDc and Macro domains were frequent among DMPs whereas glycosylation, myristoylation and RGD motifs were abundant among MMP. The proteins involved in mimicry were visualised as a SARS-CoV-2 mimicry interaction network. The host proteins were enriched in multiple CVD pathways indicating the role of mimicry in COVID-19 associated CVDs. Bridging nodes were identified as potential drug targets. Approved antihypertensive and anti-inflammatory drugs are proposed for repurposing against COVID-19 associated CVDs. The SARS-CoV-2 mimicry data has been updated in ImitateDB (http://imitatedb.sblab-nsit.net/SARSCoV2Mimicry). Determination of key mechanisms, proteins, pathways, drug targets and repurposing candidates is critical for developing therapeutics for SARS CoV-2 associated CVDs.

摘要

宿主蛋白模拟是病原体劫持宿主功能的一种策略。在实验和预测的 SARS-CoV-2 与人类互作组中探索了结构域和基序模拟。还添加了宿主的第一个相互作用蛋白,以捕捉相互作用的连续性。使用 NCBI CD Search 和 ScanProsite 分别注释了蛋白质的结构域和基序。具有共同宿主相互作用物和相似结构域/基序的宿主和病原体蛋白构成模拟对,表明具有全局结构相似性(结构域模拟对;DMP)或局部序列相似性(基序模拟对;MMP)。确定了 593 个 DMP 和 7,02,472 个 MMP。DMP 中频繁出现 AAA、DEXDc 和 Macro 结构域,而 MMP 中丰富的是糖基化、豆蔻酰化和 RGD 基序。作为 SARS-CoV-2 模拟相互作用网络可视化的模拟蛋白。参与模拟的宿主蛋白富集在多个 CVD 途径中,表明模拟在 COVID-19 相关 CVD 中的作用。桥接节点被鉴定为潜在的药物靶点。建议将已批准的抗高血压和抗炎药物重新用于治疗 COVID-19 相关 CVD。SARS-CoV-2 模拟数据已在 ImitateDB(http://imitatedb.sblab-nsit.net/SARSCoV2Mimicry)中更新。确定关键机制、蛋白、途径、药物靶点和再利用候选物对于开发 SARS-CoV-2 相关 CVD 的治疗方法至关重要。

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