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分析 SARS-CoV-2 的宿主-病毒互作组,以鉴定 COVID-19 发病机制期间易感染宿主的蛋白。

Analyzing host-viral interactome of SARS-CoV-2 for identifying vulnerable host proteins during COVID-19 pathogenesis.

机构信息

Department of Pediatrics, School of Medicine, Johns Hopkins University, MD, USA.

Network Reconstruction & Analysis (NetRA) Lab, Department of Computer Applications, Sikkim University, Gangtok, India.

出版信息

Infect Genet Evol. 2021 Sep;93:104921. doi: 10.1016/j.meegid.2021.104921. Epub 2021 May 15.

DOI:10.1016/j.meegid.2021.104921
PMID:34004362
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8123524/
Abstract

The development of therapeutic targets for COVID-19 relies on understanding the molecular mechanism of pathogenesis. Identifying genes or proteins involved in the infection mechanism is the key to shedding light on the complex molecular mechanisms. The combined effort of many laboratories distributed throughout the world has produced protein and genetic interactions. We integrated available results and obtained a host protein-protein interaction network composed of 1432 human proteins. Next, we performed network centrality analysis to identify critical proteins in the derived network. Finally, we performed a functional enrichment analysis of central proteins. We observed that the identified proteins are primarily associated with several crucial pathways, including cellular process, signaling transduction, neurodegenerative diseases. We focused on the proteins that are involved in human respiratory tract diseases. We highlighted many potential therapeutic targets, including RBX1, HSPA5, ITCH, RAB7A, RAB5A, RAB8A, PSMC5, CAPZB, CANX, IGF2R, and HSPA1A, which are central and also associated with multiple diseases.

摘要

治疗 COVID-19 的靶点的发展依赖于对发病机制的分子机制的理解。确定参与感染机制的基因或蛋白质是揭示复杂分子机制的关键。分布在世界各地的许多实验室的共同努力产生了蛋白质和遗传相互作用。我们整合了可用的结果,获得了由 1432 个人类蛋白质组成的宿主蛋白-蛋白相互作用网络。接下来,我们进行了网络中心性分析,以确定衍生网络中的关键蛋白。最后,我们对中心蛋白进行了功能富集分析。我们观察到,鉴定出的蛋白质主要与几个关键途径相关,包括细胞过程、信号转导、神经退行性疾病。我们关注参与人类呼吸道疾病的蛋白质。我们强调了许多潜在的治疗靶点,包括 RBX1、HSPA5、ITCH、RAB7A、RAB5A、RAB8A、PSMC5、CAPZB、CANX、IGF2R 和 HSPA1A,它们是中心的,也与多种疾病相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/394e/8123524/64453067c769/gr8_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/394e/8123524/f5606be83583/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/394e/8123524/e83dbd6aad74/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/394e/8123524/b0ef75226595/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/394e/8123524/7f0816bd5710/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/394e/8123524/d4d875ccd2d0/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/394e/8123524/7753f407da8d/gr6_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/394e/8123524/c23eb90ccb74/gr7_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/394e/8123524/64453067c769/gr8_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/394e/8123524/f5606be83583/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/394e/8123524/e83dbd6aad74/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/394e/8123524/b0ef75226595/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/394e/8123524/7f0816bd5710/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/394e/8123524/d4d875ccd2d0/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/394e/8123524/7753f407da8d/gr6_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/394e/8123524/c23eb90ccb74/gr7_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/394e/8123524/64453067c769/gr8_lrg.jpg

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