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对 MERS-CoV 和 SARS-CoV/CoV-2 的人蛋白结构域靶标和宿主样相互作用基序的分析推断冠状病毒的分子模拟。

The analysis on the human protein domain targets and host-like interacting motifs for the MERS-CoV and SARS-CoV/CoV-2 infers the molecular mimicry of coronavirus.

机构信息

Unidad de Investigación Biomédica de Zacatecas, Instituto Mexicano Del Seguro Social, Zacatecas, México.

Laboratorio de Inmunología y Biología Celular y Molecular, Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, San Luis Potosí, México.

出版信息

PLoS One. 2021 Feb 17;16(2):e0246901. doi: 10.1371/journal.pone.0246901. eCollection 2021.

Abstract

The MERS-CoV, SARS-CoV, and SARS-CoV-2 are highly pathogenic viruses that can cause severe pneumonic diseases in humans. Unfortunately, there is a non-available effective treatment to combat these viruses. Domain-motif interactions (DMIs) are an essential means by which viruses mimic and hijack the biological processes of host cells. To disentangle how viruses achieve this process can help to develop new rational therapies. Data mining was performed to obtain DMIs stored as regular expressions (regexp) in 3DID and ELM databases. The mined regexp information was mapped on the coronaviruses' proteomes. Most motifs on viral protein that could interact with human proteins are shared across the coronavirus species, indicating that molecular mimicry is a common strategy for coronavirus infection. Enrichment ontology analysis for protein domains showed a shared biological process and molecular function terms related to carbon source utilization and potassium channel regulation. Some of the mapped motifs were nested on B, and T cell epitopes, suggesting that it could be as an alternative way for reverse vaccinology. The information obtained in this study could be used for further theoretic and experimental explorations on coronavirus infection mechanism and development of medicines for treatment.

摘要

MERS-CoV、SARS-CoV 和 SARS-CoV-2 是高致病性病毒,可导致人类严重的肺部疾病。不幸的是,目前尚无有效的治疗方法来对抗这些病毒。结构域基序相互作用(DMIs)是病毒模拟和劫持宿主细胞生物过程的重要手段。阐明病毒如何实现这一过程有助于开发新的合理疗法。通过数据挖掘从 3DID 和 ELM 数据库中获取以正则表达式(regexp)形式存储的 DMIs。挖掘出的 regexp 信息映射到冠状病毒的蛋白质组上。与人类蛋白相互作用的病毒蛋白上的大多数基序在冠状病毒种间共享,表明分子模拟是冠状病毒感染的常见策略。对蛋白质结构域的富集本体论分析显示,与碳源利用和钾通道调节相关的共享生物学过程和分子功能术语。一些映射的基序嵌套在 B 和 T 细胞表位上,表明它可能是反向疫苗学的另一种方法。本研究获得的信息可用于进一步探索冠状病毒感染机制和开发治疗药物的理论和实验。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb0c/7888644/0865c43b2377/pone.0246901.g001.jpg

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